21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

Regulatory requirements for nuclear power plant site selection in Malaysia-a review.

PubMed

Basri, N A; Hashim, S; Ramli, A T; Bradley, D A; Hamzah, K

2016-12-01

Malaysia has initiated a range of pre-project activities in preparation for its planned nuclear power programme. Clearly one of the first steps is the selection of sites that are deemed suitable for the construction and operation of a nuclear power plant. Here we outline the Malaysian regulatory requirements for nuclear power plant site selection, emphasizing details of the selection procedures and site characteristics needed, with a clear focus on radiation safety and radiation protection in respect of the site surroundings. The Malaysia Atomic Energy Licensing Board (AELB) site selection guidelines are in accord with those provided in International Atomic Energy Agency (IAEA) and United Stated Nuclear Regulatory Commission (USNRC) documents. To enhance the suitability criteria during selection, as well as to assist in the final decision making process, possible assessments using the site selection characteristics and information are proposed.

Trip report on IAEA Training Workshop on Implementation of Integrated Management Systems for Research Reactors (T3-TR-45496).

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

Pratt, Richard J.

2013-11-01

From 17-21 June 2013, Sandia National Laboratories, Technical Area-V (SNL TA-V) represented the United States Department of Energy/National Nuclear Security Administration (DOE/NNSA) at the International Atomic Energy Agency (IAEA) Training Workshop (T3-TR-45486). This report gives a breakdown of the IAEA regulatory structure for those unfamiliar, and the lessons learned and observations that apply to SNL TA-V that were obtained from the workshop. The Safety Report Series, IAEA workshop final report, and SNL TA-V presentation are included as attachments.

9 CFR 124.22 - Revision of regulatory review period determination.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Revision of regulatory review period determination. 124.22 Section 124.22 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PATENT TERM RESTORATION Regulatory Review...

9 CFR 124.22 - Revision of regulatory review period determination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Revision of regulatory review period determination. 124.22 Section 124.22 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PATENT TERM RESTORATION Regulatory Review...

9 CFR 124.22 - Revision of regulatory review period determination.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Revision of regulatory review period determination. 124.22 Section 124.22 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PATENT TERM RESTORATION Regulatory Review...

9 CFR 124.22 - Revision of regulatory review period determination.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Revision of regulatory review period determination. 124.22 Section 124.22 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PATENT TERM RESTORATION Regulatory Review...

Improving Quality and Access to Radiation Therapy-An IAEA Perspective.

PubMed

Abdel-Wahab, May; Zubizarreta, Eduardo; Polo, Alfredo; Meghzifene, Ahmed

2017-04-01

The International Atomic Energy Agency (IAEA) has been involved in radiation therapy since soon after its creation in 1957. In response to the demands of Member States, the IAEA׳s activities relating to radiation therapy have focused on supporting low- and middle-income countries to set up radiation therapy facilities, expand the scope of treatments, or gradually transition to new technologies. In addition, the IAEA has been very active in providing internationally harmonized guidelines on clinical, dosimetry, medical physics, and safety aspects of radiation therapy. IAEA clinical research has provided evidence for treatment improvement as well as highly effective resource-sparing interventions. In the process, training of researchers occurs through this program. To provide this support, the IAEA works with its Member States and multiple partners worldwide through several mechanisms. In this article, we review the main activities conducted by the IAEA in support to radiation therapy. IAEA support has been crucial for achieving tangible results in many low- and middle-income countries. However, long-term sustainability of projects can present a challenge, especially when considering health budget constraints and the brain drain of skilled professionals. The need for support remains, with more than 90% of patients in low-income countries lacking access to radiotherapy. Thus, the IAEA is expected to continue its support and strengthen quality radiation therapy treatment of patients with cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

21 CFR 60.28 - Time frame for determining regulatory review periods.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Time frame for determining regulatory review periods. 60.28 Section 60.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.28 Time frame for...

USSP-IAEA WORKSHOP ON ADVANCED SENSORS FOR SAFEGUARDS.

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

PEPPER,S.; QUEIROLO, A.; ZENDEL, M.

2007-11-13

The IAEA Medium Term Strategy (2006-2011) defines a number of specific goals in respect to the IAEA's ability to provide assurances to the international community regarding the peaceful use of nuclear energy through States adherences to their respective non-proliferation treaty commitments. The IAEA has long used and still needs the best possible sensors to detect and measure nuclear material. The Department of Safeguards, recognizing the importance of safeguards-oriented R&D, especially targeting improved detection capabilities for undeclared facilities, materials and activities, initiated a number of activities in early 2005. The initiatives included letters to Member State Support Programs (MSSPs), personal contactsmore » with known technology holders, topical meetings, consultant reviews of safeguards technology, and special workshops to identify new and novel technologies and methodologies. In support of this objective, the United States Support Program to IAEA Safeguards hosted a workshop on ''Advanced Sensors for Safeguards'' in Santa Fe, New Mexico, from April 23-27, 2007. The Organizational Analysis Corporation, a U.S.-based management consulting firm, organized and facilitated the workshop. The workshop's goal was to help the IAEA identify and plan for new sensors for safeguards implementation. The workshop, which was attended by representatives of seven member states and international organizations, included presentations by technology holders and developers on new technologies thought to have relevance to international safeguards, but not yet in use by the IAEA. The presentations were followed by facilitated breakout sessions where the participants considered two scenarios typical of what IAEA inspectors might face in the field. One scenario focused on an enrichment plant; the other scenario focused on a research reactor. The participants brainstormed using the technologies presented by the participants and other technologies known to them to propose

78 FR 29062 - 2006 Biennial Regulatory Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... Regulatory Review AGENCY: Federal Communications Commission. ACTION: Correcting amendments. SUMMARY: The Federal Communications Commission published a document in the Federal Register on February 6, 2013 (78 FR... INFORMATION: The Federal Communications Commission published a rule on February 6, 2013 which became effective...

Use of Advanced Tsunami Hazard Assessment Techniques and Tsunami Source Characterizations in U.S. and International Nuclear Regulatory Activities

NASA Astrophysics Data System (ADS)

Kammerer, A. M.; Godoy, A. R.

2009-12-01

In response to the 2004 Indian Ocean Tsunami, as well as the anticipation of the submission of license applications for new nuclear facilities, the United States Nuclear Regulatory Commission (US NRC) initiated a long-term research program to improve understanding of tsunami hazard levels for nuclear power plants and other coastal facilities in the United States. To undertake this effort, the US NRC organized a collaborative research program jointly undertaken with researchers at the United States Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA) for the purpose of assessing tsunami hazard on the Atlantic and Gulf Coasts of the United States. This study identified and modeled both seismic and landslide tsunamigenic sources in the near- and far-field. The results from this work are now being used directly as the basis for the review of tsunami hazard at potential nuclear plant sites. This application once again shows the importance that the earth sciences can play in addressing issues of importance to society. Because the Indian Ocean Tsunami was a global event, a number of cooperative international activities have also been initiated within the nuclear community. The results of US efforts are being incorporated into updated regulatory guidance for both the U.S. Nuclear Regulatory Commission and the United Nation’s International Atomic Energy Agency (IAEA). Coordinated efforts are underway to integrate state-of-the art tsunami warning tools developed by NOAA into NRC and IAEA activities. The goal of the warning systems project is to develop automated protocols that allow scientists at these agencies to have up-to-the minute user-specific information in hand shortly after a potential tsunami has been identified by the US Tsunami Warning System. Lastly, USGS and NOAA scientists are assisting the NRC and IAEA in a special Extra-Budgetary Program (IAEA EBP) on tsunami being coordinated by the IAEA’s International Seismic Safety

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.

40 CFR 63.851 - Regulatory authority review procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Regulatory authority review procedures... PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants for Primary Aluminum Reduction Plants...

40 CFR 63.851 - Regulatory authority review procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 10 2011-07-01 2011-07-01 false Regulatory authority review procedures... PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants for Primary Aluminum Reduction Plants...

40 CFR 63.851 - Regulatory authority review procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 11 2013-07-01 2013-07-01 false Regulatory authority review procedures... PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants for Primary Aluminum Reduction Plants...

40 CFR 63.851 - Regulatory authority review procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 11 2012-07-01 2012-07-01 false Regulatory authority review procedures... PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants for Primary Aluminum Reduction Plants...

Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice.

PubMed

McCarty, Lynn S; Borgert, Christopher J; Mihaich, Ellen M

2012-07-01

There is an ongoing discussion on the provenance of toxicity testing data regarding how best to ensure its validity and credibility. A central argument is whether journal peer-review procedures are superior to Good Laboratory Practice (GLP) standards employed for compliance with regulatory mandates. We sought to evaluate the rationale for regulatory decision making based on peer-review procedures versus GLP standards. We examined pertinent published literature regarding how scientific data quality and validity are evaluated for peer review, GLP compliance, and development of regulations. Some contend that peer review is a coherent, consistent evaluative procedure providing quality control for experimental data generation, analysis, and reporting sufficient to reliably establish relative merit, whereas GLP is seen as merely a tracking process designed to thwart investigator corruption. This view is not supported by published analyses pointing to subjectivity and variability in peer-review processes. Although GLP is not designed to establish relative merit, it is an internationally accepted quality assurance, quality control method for documenting experimental conduct and data. Neither process is completely sufficient for establishing relative scientific soundness. However, changes occurring both in peer-review processes and in regulatory guidance resulting in clearer, more transparent communication of scientific information point to an emerging convergence in ensuring information quality. The solution to determining relative merit lies in developing a well-documented, generally accepted weight-of-evidence scheme to evaluate both peer-reviewed and GLP information used in regulatory decision making where both merit and specific relevance inform the process.

75 FR 32479 - Determination of Regulatory Review Period for Purposes of Patent Extension; ABLAVAR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-2009-E-0165 and FDA-2009-E-0169] Determination of Regulatory Review Period for Purposes of Patent Extension... Administration (FDA) has determined the regulatory review period for ABLAVAR (previously the trade name of the...

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Argentina.

PubMed

Kairiyama, Eulogia; Morales Pedraza, Jorge

2009-05-01

Tissue banking activities in Argentina started in 1993. The regulatory and controlling national authority on organ, tissue and cells for transplantation activity is the National Unique Coordinating Central Institute for Ablation and Implant (INCUCAI). Three tissue banks were established under the IAEA program and nine other banks participated actively in the implementation of this program. As result of the implementation of the IAEA program in Argentina and the work done by the established tissue banks, more and more hospitals are now using, in a routine manner, radiation sterilised tissues processed by these banks. During the period 1992-2005, more than 21 016 tissues were produced and irradiated in the tissue banks participating in the IAEA program. Within the framework of the training component of the IAEA program, Argentina has been selected to host the Regional Training Centre for Latin American. In this centre, tissue bank operators and medical personal from Latin American countries were trained. Since 1999, Argentina has organised four regular regional training courses and two virtual regional training courses. More than twenty (20) tissue bank operators and medical personnel from Argentina were trained under the IAEA program in the six courses organised in the country. In general, ninety (96) tissue bank operators and medical personnel from eight Latin-American countries were trained in the Buenos Aires regional training centre. From Argentina 16 students graduated in these courses.

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

The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

PubMed

Keyter, Andrea; Gouws, Joey; Salek, Sam; Walker, Stuart

2018-01-01

The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.

76 FR 18134 - Reducing Regulatory Burden; Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... PENSION BENEFIT GUARANTY CORPORATION 29 CFR Chapter XL Reducing Regulatory Burden; Review Under E.O. 13563 AGENCY: Pension Benefit Guaranty Corporation. ACTION: Request for comments. SUMMARY: The Pension Benefit Guaranty Corporation (PBGC) is reviewing its regulations in response to the President's...

Regulatory cross-cutting topics for fuel cycle facilities.

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

Denman, Matthew R.; Brown, Jason; Goldmann, Andrew Scott

This report overviews crosscutting regulatory topics for nuclear fuel cycle facilities for use in the Fuel Cycle Research & Development Nuclear Fuel Cycle Evaluation and Screening study. In particular, the regulatory infrastructure and analysis capability is assessed for the following topical areas: Fire Regulations (i.e., how applicable are current Nuclear Regulatory Commission (NRC) and/or International Atomic Energy Agency (IAEA) fire regulations to advance fuel cycle facilities) Consequence Assessment (i.e., how applicable are current radionuclide transportation tools to support risk-informed regulations and Level 2 and/or 3 PRA) While not addressed in detail, the following regulatory topic is also discussed: Integrated Security,more » Safeguard and Safety Requirement (i.e., how applicable are current Nuclear Regulatory Commission (NRC) regulations to future fuel cycle facilities which will likely be required to balance the sometimes conflicting Material Accountability, Security, and Safety requirements.)« less

Nuclear Regulatory Commission activities to prepare for reviewing license applications and issuing licenses

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

Uleck, R.B.; DeFino, C.V.

1991-12-31

The Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) assigned States the responsibility to provide for disposal of commercial low-level radioactive waste (LLRW) by 1993. The LLRWPAA also required the US Nuclear Regulatory Commission (NRC) to establish procedures and develop the technical review capability to process license applications for new LLRW disposal facilities. Under the LLRWPAA, NRC is required, to the extent practicable, to complete its review of an LLRW disposal facility license application within 15 months of its submittal by a State. This provision of the LLRWPAA helps ensure that NRC, in addition to protecting public health andmore » safety and the environment, facilitates States` achievement of LLRWPAA milestones for new facility development. A timely NRC review is needed for States to accomplish their objective of having new disposal facilities in operation on the dates prescribed in the LLRWPAA. To help assure NRC and States` compliance with the provisions of the LLRWPAA, NRC has developed a licensing review strategy that includes: (1) the further development of regulatory guidance, (2) enhancement of licensing review capability, and (3) prelicensing regulatory consultation with potential applicants.« less

OSHA's renewed mandate for regulatory flexibility review: in support of the 1984 ethylene oxide standard.

PubMed

LaMontagne, A D; Kelsey, K T

1998-08-01

The Regulatory Flexibility Act of 1980 requires that all federal agencies consider the impact of regulations on small entities. One of the provisions of the Act requires review of regulations ever 10 years to determine whether such regulations should be continued without changes, rescinded, or amended to make them more effective or less burdensome on businesses. The Small Business Regulatory Enforcement Fairness Act (SBREFA) of 1996 amended and expanded the Regulatory Flexibility Act. Most significantly, SBREFA entitles aggrieved small entities or their representative (e.g., trade associations) to sue OSHA for failure to fulfill Regulatory Flexibility Act requirements. In response to this new political reality, OSHA held the first public meeting of their kind in June of 1997 to gather information on the ethylene oxide and lock-out/tag-out standards for the purposes of Regulatory Flexibility review. This paper presents the development of the Regulatory Flexibility review process and details our analysis of the ethylene oxide standard using OSHA's eight Regulatory Flexibility review criteria. Great progress in ethylene oxide health and safety has been made since the promulgation of the standard in 1984, including a considerable decrease in average workshift exposures. Yet, important concerns remain, such as the lack of safer substitutes for EtO's most common uses, the widespread occurrence of accidental exposures to EtO that are not captured by personal monitoring, and the recent increase in the occurrence of catastrophic EtO explosions. Because of the considerable study that has been devoted to EtO and to the EtO standard, there is a very strong cases for either making the EtO standard more worker protective, or continuing the standard without change while improving outreach and enforcement efforts to address shortcomings. Other valuable standards for which fewer data exist may be inappropriately threatened by the Regulatory Flexibility review process. Importantly

76 FR 11395 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... identify specific current regulations that may be outdated, ineffective, or excessively burdensome. The purpose of this regulatory review is to make the Department's regulations more effective and less... review existing significant regulations to determine if they are outmoded, ineffective, insufficient or...

9 CFR 124.23 - Final action on regulatory review period determination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND... request under § 124.22 for revision of the regulatory review period determination; (c) A due diligence...

Issues in Peer Review of the Scientific Basis for Regulatory Decisions.

ERIC Educational Resources Information Center

American Chemical Society, Washington, DC.

This document is intended to provide a discussion of the issues that need to be addressed in the development of peer review guidelines, the options for addressing the issues, and a range of views about such options. The document focuses on peer review with regard to regulatory decisions and contains major sections which deal with: (1) what should…

76 FR 47089 - Regulatory Review Schedule; Cancellation of Consultation Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule; Cancellation of Consultation Meetings AGENCY: National Indian Gaming Commission. ACTION: Notice. SUMMARY: On November 18, 2010, the National Indian Gaming Commission (NIGC) issued a Notice of Inquiry and...

Measuring the impact of medicines regulatory interventions - Systematic review and methodological considerations.

PubMed

Goedecke, Thomas; Morales, Daniel R; Pacurariu, Alexandra; Kurz, Xavier

2018-03-01

Evaluating the public health impact of regulatory interventions is important but there is currently no common methodological approach to guide this evaluation. This systematic review provides a descriptive overview of the analytical methods for impact research. We searched MEDLINE and EMBASE for articles with an empirical analysis evaluating the impact of European Union or non-European Union regulatory actions to safeguard public health published until March 2017. References from systematic reviews and articles from other known sources were added. Regulatory interventions, data sources, outcomes of interest, methodology and key findings were extracted. From 1246 screened articles, 229 were eligible for full-text review and 153 articles in English language were included in the descriptive analysis. Over a third of articles studied analgesics and antidepressants. Interventions most frequently evaluated are regulatory safety communications (28.8%), black box warnings (23.5%) and direct healthcare professional communications (10.5%); 55% of studies measured changes in drug utilization patterns, 27% evaluated health outcomes, and 18% targeted knowledge, behaviour or changes in clinical practice. Unintended consequences like switching therapies or spill-over effects were rarely evaluated. Two-thirds used before-after time series and 15.7% before-after cross-sectional study designs. Various analytical approaches were applied including interrupted time series regression (31.4%), simple descriptive analysis (28.8%) and descriptive analysis with significance tests (23.5%). Whilst impact evaluation of pharmacovigilance and product-specific regulatory interventions is increasing, the marked heterogeneity in study conduct and reporting highlights the need for scientific guidance to ensure robust methodologies are applied and systematic dissemination of results occurs. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of

Proceedings of the IAEA specialists` meeting on cracking in LWR RPV head penetrations

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

Pugh, C.E.; Raney, S.J.

1996-07-01

This report contains 17 papers that were presented in four sessions at the IAEA Specialists` meeting on Cracking in LWR RPV Head Penetrations held at ASTM Headquarters in Philadelphia on May 2-3, 1995. The papers are compiled here in the order that presentations were made in the sessions, and they relate to operational observations, inspection techniques, analytical modeling, and regulatory control. The goal of the meeting was to allow international experts to review experience in the field of ensuring adequate performance of reactor pressure vessel (RPV) heads and penetrations. The emphasis was to allow a better understanding of RPV materialmore » behavior, to provide guidance supporting reliability and adequate performance, and to assist in defining directions for further investigations. The international nature of the meeting is illustrated by the fact that papers were presented by researchers from 10 countries. There were technical experts present form other countries who participated in discussions of the results presented. This present document incorporates the final version of the papers as received from the authors. The final chapter includes conclusions and recommendations. Individual papers have been cataloged separately.« less

Improving the Transparency of IAEA Safeguards Reporting

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

Toomey, Christopher; Hayman, Aaron M.; Wyse, Evan T.

2011-07-17

In 2008, the Standing Advisory Group on Safeguards Implementation (SAGSI) indicated that the International Atomic Energy Agency's (IAEA) Safeguards Implementation Report (SIR) has not kept pace with the evolution of safeguards and provided the IAEA with a set of recommendations for improvement. The SIR is the primary mechanism for providing an overview of safeguards implementation in a given year and reporting on the annual safeguards findings and conclusions drawn by the Secretariat. As the IAEA transitions to State-level safeguards approaches, SIR reporting must adapt to reflect these evolutionary changes. This evolved report will better reflect the IAEA's transition to amore » more qualitative and information-driven approach, based upon State-as-a-whole considerations. This paper applies SAGSI's recommendations to the development of multiple models for an evolved SIR and finds that an SIR repurposed as a 'safeguards portal' could significantly enhance information delivery, clarity, and transparency. In addition, this paper finds that the 'portal concept' also appears to have value as a standardized information presentation and analysis platform for use by Country Officers, for continuity of knowledge purposes, and the IAEA Secretariat in the safeguards conclusion process. Accompanying this paper is a fully functional prototype of the 'portal' concept, built using commercial software and IAEA Annual Report data.« less

Certified reference materials for radionuclides in Bikini Atoll sediment (IAEA-410) and Pacific Ocean sediment (IAEA-412).

PubMed

Pham, M K; van Beek, P; Carvalho, F P; Chamizo, E; Degering, D; Engeler, C; Gascó, C; Gurriaran, R; Hanley, O; Harms, A V; Herrmann, J; Hult, M; Ikeuchi, Y; Ilchmann, C; Kanisch, G; Kis-Benedek, G; Kloster, M; Laubenstein, M; Llaurado, M; Mas, J L; Nakano, M; Nielsen, S P; Osvath, I; Povinec, P P; Rieth, U; Schikowski, J; Smedley, P A; Suplinska, M; Sýkora, I; Tarjan, S; Varga, B; Vasileva, E; Zalewska, T; Zhou, W

2016-03-01

The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: (40)K, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (234)U, (238)U, (239)Pu, (239+240)Pu and (241)Am for IAEA-410 and (40)K, (137)Cs, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (235)U, (238)U, (239)Pu, (240)Pu and (239+240)Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training. Copyright © 2015 Elsevier Ltd. All rights reserved.

9 CFR 124.23 - Final action on regulatory review period determination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 180-day period for filing a due diligence petition under § 124.30 unless it receives: (a) New... request under § 124.22 for revision of the regulatory review period determination; (c) A due diligence...

76 FR 6094 - FAA Public Forum To Conduct Regulatory Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Parts 27 and 29 FAA Public Forum To Conduct Regulatory Review AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of.... Attendees are not required to register for the Heli-Expo conference to participate in this public forum. FOR...

76 FR 16700 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Regulation and Regulatory Review,'' the Department of Defense invites public comments on how it can change... to determine how its regulations can increase efficiency, transparency, and provide accountability...

78 FR 23199 - NASA FAR Supplement Regulatory Review No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... 2700-AE01 NASA FAR Supplement Regulatory Review No. 1 AGENCY: National Aeronautics and Space Administration. ACTION: Proposed rule. SUMMARY: NASA is updating the NASA FAR Supplement (NFS) with the goal of... existing regulations. The revisions to this rule are part of NASA's retrospective plan under EO 13563...

Measuring the impact of medicines regulatory interventions – Systematic review and methodological considerations

PubMed Central

Morales, Daniel R.; Pacurariu, Alexandra; Kurz, Xavier

2017-01-01

Aims Evaluating the public health impact of regulatory interventions is important but there is currently no common methodological approach to guide this evaluation. This systematic review provides a descriptive overview of the analytical methods for impact research. Methods We searched MEDLINE and EMBASE for articles with an empirical analysis evaluating the impact of European Union or non‐European Union regulatory actions to safeguard public health published until March 2017. References from systematic reviews and articles from other known sources were added. Regulatory interventions, data sources, outcomes of interest, methodology and key findings were extracted. Results From 1246 screened articles, 229 were eligible for full‐text review and 153 articles in English language were included in the descriptive analysis. Over a third of articles studied analgesics and antidepressants. Interventions most frequently evaluated are regulatory safety communications (28.8%), black box warnings (23.5%) and direct healthcare professional communications (10.5%); 55% of studies measured changes in drug utilization patterns, 27% evaluated health outcomes, and 18% targeted knowledge, behaviour or changes in clinical practice. Unintended consequences like switching therapies or spill‐over effects were rarely evaluated. Two‐thirds used before–after time series and 15.7% before–after cross‐sectional study designs. Various analytical approaches were applied including interrupted time series regression (31.4%), simple descriptive analysis (28.8%) and descriptive analysis with significance tests (23.5%). Conclusion Whilst impact evaluation of pharmacovigilance and product‐specific regulatory interventions is increasing, the marked heterogeneity in study conduct and reporting highlights the need for scientific guidance to ensure robust methodologies are applied and systematic dissemination of results occurs. PMID:29105853

IAEA support to medical physics in nuclear medicine.

PubMed

Meghzifene, Ahmed; Sgouros, George

2013-05-01

Through its programmatic efforts and its publications, the International Atomic Energy Agency (IAEA) has helped define the role and responsibilities of the nuclear medicine physicist in the practice of nuclear medicine. This paper describes the initiatives that the IAEA has undertaken to support medical physics in nuclear medicine. In 1984, the IAEA provided guidance on how to ensure that the equipment used for detecting, imaging, and quantifying radioactivity is functioning properly (Technical Document [TECDOC]-137, "Quality Control of Nuclear Medicine Instruments"). An updated version of IAEA-TECDOC-137 was issued in 1991 as IAEA-TECDOC-602, and this included new chapters on scanner-computer systems and single-photon emission computed tomography systems. Nuclear medicine physics was introduced as a part of a project on radiation imaging and radioactivity measurements in the 2002-2003 IAEA biennium program in Dosimetry and Medical Radiation Physics. Ten years later, IAEA activities in this field have expanded to cover quality assurance (QA) and quality control (QC) of nuclear medicine equipment, education and clinical training, professional recognition of the role of medical physicists in nuclear medicine physics, and finally, the coordination of research and development activities in internal dosimetry. As a result of these activities, the IAEA has received numerous requests to support the development and implementation of QA or QC programs for radioactivity measurements in nuclear medicine in many Member States. During the last 5 years, support was provided to 20 Member States through the IAEA's technical cooperation programme. The IAEA has also supported education and clinical training of medical physicists. This type of support has been essential for the development and expansion of the Medical Physics profession, especially in low- and middle-income countries. The need for basic as well as specialized clinical training in medical physics was identified as a

The identification of cis-regulatory elements: A review from a machine learning perspective.

PubMed

Li, Yifeng; Chen, Chih-Yu; Kaye, Alice M; Wasserman, Wyeth W

2015-12-01

The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Regulatory and legal review of automated and connected truck platooning technology.

DOT National Transportation Integrated Search

2017-05-01

Commercial truck platooning is a relatively novel concept in Texas and around the country. This white paper : presents the results of a review of state and federal code to identify regulatory and legislative hurdles that : may delay or deter platooni...

An IAEA multi-technique X-ray spectrometry endstation at Elettra Sincrotrone Trieste: benchmarking results and interdisciplinary applications.

PubMed

Karydas, Andreas Germanos; Czyzycki, Mateusz; Leani, Juan José; Migliori, Alessandro; Osan, Janos; Bogovac, Mladen; Wrobel, Pawel; Vakula, Nikita; Padilla-Alvarez, Roman; Menk, Ralf Hendrik; Gol, Maryam Ghahremani; Antonelli, Matias; Tiwari, Manoj K; Caliri, Claudia; Vogel-Mikuš, Katarina; Darby, Iain; Kaiser, Ralf Bernd

2018-01-01

The International Atomic Energy Agency (IAEA) jointly with the Elettra Sincrotrone Trieste (EST) operates a multipurpose X-ray spectrometry endstation at the X-ray Fluorescence beamline (10.1L). The facility has been available to external users since the beginning of 2015 through the peer-review process of EST. Using this collaboration framework, the IAEA supports and promotes synchrotron-radiation-based research and training activities for various research groups from the IAEA Member States, especially those who have limited previous experience and resources to access a synchrotron radiation facility. This paper aims to provide a broad overview about various analytical capabilities, intrinsic features and performance figures of the IAEA X-ray spectrometry endstation through the measured results. The IAEA-EST endstation works with monochromatic X-rays in the energy range 3.7-14 keV for the Elettra storage ring operating at 2.0 or 2.4 GeV electron energy. It offers a combination of different advanced analytical probes, e.g. X-ray reflectivity, X-ray absorption fine-structure measurements, grazing-incidence X-ray fluorescence measurements, using different excitation and detection geometries, and thereby supports a comprehensive characterization for different kinds of nanostructured and bulk materials.

RECRUITMENT OF U.S. CITIZENS FOR VACANCIES IN IAEA SAFEGUARDS

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

PEPPER,S.E.; DECARO,D.; WILLIAMS,G.

The International Atomic Energy Agency (IAEA) relies on its member states to assist with recruiting qualified individuals for positions within the IAEA's secretariat. It is important that persons within and outside the US nuclear and safeguards industries become aware of career opportunities available at the IAEA, and informed about important vacancies. The IAEA has established an impressive web page to advertise opportunities for employment. However, additional effort is necessary to ensure that there is sufficient awareness in the US of these opportunities, and assistance for persons interested in taking positions at the IAEA. In 1998, the Subgroup on Safeguards Technicalmore » Support (SSTS) approved a special task under the US Support Program to IAEA Safeguards (USSP) for improving US efforts to identify qualified candidates for vacancies in IAEA's Department of Safeguards. The International Safeguards Project Office (ISPO) developed a plan that includes increased advertising, development of a web page to support US recruitment efforts, feedback from the US Mission in Vienna, and interaction with other recruitment services provided by US professional organizations. The main purpose of this effort is to educate US citizens about opportunities at the IAEA so that qualified candidates can be identified for the IAEA's consideration.« less

76 FR 10527 - Regulatory Flexibility Act: Section 610 Review of National Organic Program Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

...: This document announces the Agricultural Marketing Service's (AMS) plans to review the National Organic... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 205 [Document Number AMS-NOP-11-0005; NOP-11-01] Regulatory Flexibility Act: Section 610 Review of National Organic Program...

Applications of pharmacogenomics in regulatory science: a product life cycle review.

PubMed

Tan-Koi, W C; Leow, P C; Teo, Y Y

2018-05-22

With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents. Approximately one-third of Food and Drug Administration (FDA)-approved drugs with PGx information in drug labels and half of the European labels posted on PharmGKB website contain recommendations on genetic testing. The drugs affected 19 and 15 World Health Organization Anatomical Therapeutic Chemical drug classes (fourth level) in the United States and Europe, respectively, with protein kinase inhibitors (13 drugs in the United States and 16 drugs in Europe) being most prevalent. Topics of emerging interest were novel technologies, adaptive design in clinical trial and sample collection.

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale

PubMed Central

Berry, Colin; Brusick, David; Cohen, Samuel M.; Hardisty, Jerry F.; Grotz, V. Lee; Williams, Gary M.

2016-01-01

ABSTRACT Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels. PMID:27652616

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

PubMed

Berry, Colin; Brusick, David; Cohen, Samuel M; Hardisty, Jerry F; Grotz, V Lee; Williams, Gary M

2016-01-01

Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment: A Systematic Review of the Literature

PubMed Central

Bujar, Magdalena; McAuslane, Neil; Walker, Stuart R.; Salek, Sam

2017-01-01

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general

Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment: A Systematic Review of the Literature.

PubMed

Bujar, Magdalena; McAuslane, Neil; Walker, Stuart R; Salek, Sam

2017-01-01

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general

A Review of International Telecommunications Industry Issues, Structure, and Regulatory Problems.

ERIC Educational Resources Information Center

Cole, Jack E.; And Others

Industry structure studies prior to 1968 are briefly reviewed, and an overview of industrial and technological developments up to the present is provided through synopses of more recent studies. Areas covered include overseas telephone and record carriers; the creation of the Communications Satellite Corporation; the current regulatory and…

Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study

PubMed Central

Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

2015-01-01

Aims Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). Methods We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA’s 210 day regulatory deadline. Results Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276–406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Conclusions Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. PMID:25808713

Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study.

PubMed

Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

2015-10-01

Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA's 210 day regulatory deadline. Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276-406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. © 2015 The British Pharmacological Society.

The drug regulatory and review process in Guyana.

PubMed

Woo-Ming, R B

1993-01-01

After the old "Sale of Food and Drugs" Ordinance, Cap. 144 was repealed, the new Food and Drugs Act was enacted in 1971. This new Act has considerable flexibility and gives the Minister extensive authority to make Regulations (for carrying out the purposes and provisions of the Act). The Act controls the manufacture, importation, sale, advertising, labeling, packaging, and distribution of drug samples, and the testing of drugs. The Act also controls raw materials and finished products of drugs at the point of entry into the country, with a single agency coordinating both the inspection and analytical services. Developing countries could ensure the procurement of safe, good quality, and effective drugs and devices with the enactment of a similar Food and Drugs Act only. Rapid assessment of Drug Safety, Quality and Efficacy is done through Guyana's participation in the WHO Certification Scheme on the Quality of Pharmaceutical Products moving in International Commerce. This certification scheme is highly commendable especially to third-world countries. The Food and Drug Regulations (1977) have several unique features for drug, cosmetic and device control and they allow for a system of centralized control with limited staff to enforce the legislation. In summary, enforcement of legislative control of imported pharmaceuticals and product evaluation can be considered strong points in the drug regulatory and review process in Guyana. A cautious attitude is observed so as to ensure efficacy, safety, and quality of drugs entering the market. This Drug Regulatory and Review Process is recommended for implementation by third-world countries with outdated drug legislation.(ABSTRACT TRUNCATED AT 250 WORDS)

Evolution in performance assessment modeling as a result of regulatory review

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

Rowat, J.H.; Dolinar, G.M.; Stephens, M.E.

1995-12-31

AECL is planning to build the IRUS (Intrusion Resistant Underground Structure) facility for near-surface disposal of LLRW. The PSAR (preliminary safety assessment report) was subject to an initial regulatory review during mid-1992. The regulatory authority provided comments on many aspects of the safety assessment documentation including a number of questions on specific PA (Performance Assessment) modelling assumptions. As a result of these comments as well as a separate detailed review of the IRUS disposal concept, changes were made to the conceptual and mathematical models. The original disposal concept included a non-sorbing vault backfill, with a strong reliance on the wasteformmore » as a barrier. This concept was altered to decrease reliance on the wasteform by replacing the original backfill with a sand/clinoptilolite mix, which is a better sorber of metal cations. This change lead to changes in the PA models which in turn altered the safety case for the facility. This, and other changes that impacted performance assessment modelling are the subject of this paper.« less

76 FR 31886 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... OFFICE OF PERSONNEL MANAGEMENT 5 CFR Chapters I and XXXV 45 CFR Chapter VIII 48 CFR Chapters 16, 17, and 21 Reducing Regulatory Burden; Retrospective Review Under E.O. 13563 AGENCY: Office of Personnel Management. ACTION: Request for information. SUMMARY: The Office of Personnel Management has...

IAEA Sampling Plan

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

Geist, William H.

2017-09-15

The objectives for this presentation are to describe the method that the IAEA uses to determine a sampling plan for nuclear material measurements; describe the terms detection probability and significant quantity; list the three nuclear materials measurement types; describe the sampling method applied to an item facility; and describe multiple method sampling.

Transportation of Large Wind Components: A Permitting and Regulatory Review

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

Levine, Aaron; Cook, Jeff

This report summarizes permitting and regulatory issues associated with transporting wind turbine blades, towers, and nacelles as well as large transformers (wind components). These wind components are commonly categorized as oversized and overweight (OSOW) and require specific permit approvals from state and local jurisdictions. The report was developed based on a Quadrennial Energy Review (QER) recommendation on logistical requirements for the transportation of 'oversized or high-consequence energy materials, equipment, and components.'

Department of Energy Efforts to Promote Universal Adherence to the IAEA Additional Protocol

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

Killinger, Mark H.; Hansen, Linda H.; Kovacic, Don N.

2009-10-06

Entry-into-force of the U.S. Additional Protocol (AP) in January 2009 continues to demonstrate the ongoing commitment by the United States to promote universal adherence to the AP. The AP is a critical tool for improving the International Atomic Energy Agency’s (IAEA) capabilities to detect undeclared activities that indicate a clandestine nuclear weapons program. This is because States Parties are required to provide information about, and access to, nuclear fuel cycle activities beyond their traditional safeguards reporting requirements. As part of the U.S. AP Implementation Act and Senate Resolution of Ratification, the Administration is required to report annually to Congress onmore » measures taken to achieve the adoption of the AP in non-nuclear weapon states, as well as assistance to the IAEA to promote the effective implementation of APs in those states. A key U.S. effort in this area is being managed by the International Nuclear Safeguards and Engagement Program (INSEP) of the U.S. Department of Energy (DOE). Through new and existing bilateral cooperation agreements, INSEP has initiated technical assistance projects for AP implementation with selected non-weapon states. States with which INSEP is currently cooperating include Vietnam and Thailand, with Indonesia, Algeria, Morocco, and other countries as possible future collaborators in the area of AP implementation. The INSEP collaborative model begins with a joint assessment with our partners to identify specific needs they may have regarding entering the AP into force and any impediments to successful implementation. An action plan is then developed detailing and prioritizing the necessary joint activities. Such assistance may include: advice on developing legal frameworks and regulatory documents; workshops to promote understanding of AP requirements; training to determine possible declarable activities; assistance in developing a system to collect and submit declarations; performing industry

75 FR 55295 - List of Rules To Be Reviewed Pursuant to the Regulatory Flexibility Act

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

...-3078, IC-29408; File No. S7-20-10] List of Rules To Be Reviewed Pursuant to the Regulatory Flexibility Act AGENCY: Securities and Exchange Commission. ACTION: Publication of list of rules scheduled for review. SUMMARY: The Securities and Exchange Commission is today publishing a list of rules to be...

Harmonization of reimbursement and regulatory approval processes: a systematic review of international experiences.

PubMed

Tsoi, Bernice; Masucci, Lisa; Campbell, Kaitryn; Drummond, Michael; O'Reilly, Daria; Goeree, Ron

2013-08-01

A considerable degree of overlap exists between reimbursement and regulatory approval of health technologies, and harmonization of certain aspects is both possible and feasible. Various models to harmonization have been suggested in which a number of practical attempts have been drawn from. Based on a review of the literature, approaches can be categorized into those focused on reducing uncertainty and developing economies of scale in the evidentiary requirements; and/or aligning timeframes and logistical aspects of the review process. These strategies can further be classified based on the expected level of structural and organizational change required to implement them into the existing processes. Passive processes require less modification, whereas active processes are associated with greater restructuring. Attempts so far at harmonization have raised numerous legal and practical issues and these must be considered when introducing a more harmonized framework into the existing regulatory and reimbursement arrangements.

Participation in proficiency test for tritium strontium and caesium isotopes in seawater 2015 (IAEA-RML-2015-02)

NASA Astrophysics Data System (ADS)

Visetpotjanakit, S.; Kaewpaluek, S.

2017-06-01

A proficiency test (PT) exercise has proposed by the International Atomic Energy Agency (IAEA) in the frame of the IAEA Technical Cooperation project RAS/7/021 “Marine benchmark study on the possible impact of the Fukushima radioactive releases in the Asia-Pacific Region for Caesium Determination in Sea Water” since 2012. In 2015 the exercise was referred to Proficiency Test for Tritium, Strontium and Caesium Isotopes in Seawater 2015 (IAEA-RML-2015-02) to analyse3H, 134Cs, 137Cs and90Sr in a seawater sample. OAP was one of the 17 laboratories from 15 countries from Asia-Pacific Region who joined the PT exercise. The aim of our participation was to validate our analytical performance for the accurate determination of radionuclides in seawater by developed methods of radiochemical analysis. OAP submitted results determining the concentration for the three elements i.e. 134Cs, 137Cs and90Sr in seawater to the IAEA. A critical review was made to check suitability of our methodology and the criteria for the accuracy, precision and trueness of our data. The results of both 134Cs and 137Cs passed all criteria which were assigned “Accepted” statuses. Whereas 90Sr analysis did not pass the accuracy test therefore it was considered as “Not accepted” Our results and all other participant results with critical comments were published in the IAEA proficiency test report.

Capacity for ethical and regulatory review of herbal trials in developing countries: a case study of Moringa oleifera research in HIV-infected patients.

PubMed

Monera-Penduka, Tsitsi G; Maponga, Charles C; Morse, Gene D; Nhachi, Charles F B

2017-01-01

Lack of regulatory capacity limits the conduct of ethical and rigorous trials of herbal medicines in developing countries. Sharing ethical and regulatory experiences of successful herbal trials may accelerate the field while assuring human subjects protection. The methods and timelines for the ethical and regulatory review processes for the first drug regulatory authority approved herbal trial in Zimbabwe are described in this report. The national drug regulatory authority and ethics committee were engaged for pre-submission discussions. Six applications were submitted. Application procedures and communications with the various regulatory and ethics review boards were reviewed. Key issues raised and timelines for communications were summarized. There was no special framework for the approval of herbal trials. One local institutional review committee granted an exemption. Key issues raised for revision were around pre-clinical efficacy and safety data, standardization and quality assurance of the intervention as well as consenting procedures. Approval timelines ranged between eight and 72 weeks. In the absence of a defined framework for review of herbal trials, approval processes can be delayed. Dialogue between researchers and regulators is important for successful and efficient protocol approval for herbal trials in developing countries. The study was registered prospectively on August 3, 2011 with clinicaltrials.gov (NCT01410058).

A systematic literature review of the effectiveness of occupational health and safety regulatory enforcement.

PubMed

Tompa, Emile; Kalcevich, Christina; Foley, Michael; McLeod, Chris; Hogg-Johnson, Sheilah; Cullen, Kim; MacEachen, Ellen; Mahood, Quenby; Irvin, Emma

2016-11-01

We aimed to determine the strength of evidence on the effectiveness of legislative and regulatory policy levers in creating incentives for organizations to improve occupational health and safety processes and outcomes. A systematic review was undertaken to assess the strength of evidence on the effectiveness of specific policy levers using a "best-evidence" synthesis approach. A structured literature search identified 11,947 citations from 13 peer-reviewed literature databases. Forty-three studies were retained for synthesis. Strong evidence was identified for three out of nine clusters. There is strong evidence that several OHS policy levers are effective in terms of reducing injuries and/or increasing compliance with legislation. This study adds to the evidence on OHS regulatory effectiveness from an earlier review. In addition to new evidence supporting previous study findings, it included new categories of evidence-compliance as an outcome, nature of enforcement, awareness campaigns, and smoke-free workplace legislation. Am. J. Ind. Med. 59:919-933, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS, INFCIRC/540 (Corrected) VOLUME II/III IAEA COMMITTEE 24, Major Issues Underlying the Model Additional Protocol (1996-1997).

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

Rosenthal, M.D.; Saum-Manning, L.; Houck, F.

Volume I of this Review traces the origins of the Model Additional Protocol. It covers the period from 1991, when events in Iraq triggered an intensive review of the safeguards system, until 1996, when the IAEA Board of Governors established Committee 24 to negotiate a new protocol to safeguards agreement. The period from 1991-1996 set the stage for this negotiation and shaped its outcome in important ways. During this 5-year period, many proposals for strengthening safeguards were suggested and reviewed. Some proposals were dropped, for example, the suggestion by the IAEA Secretariat to verify certain imports, and others were refined.more » A rough consensus was established about the directions in which the international community wanted to go, and this was reflected in the draft of an additional protocol that was submitted to the IAEA Board of Governors on May 6, 1996 in document GOV/2863, Strengthening the Effectiveness and Improving the Efficiency of the Safeguards System - Proposals For Implementation Under Complementary Legal Authority, A Report by the Director General. This document ended with a recommendation that, 'the Board, through an appropriate mechanism, finalize the required legal instrument taking as a basis the draft protocol proposed by the Secretariat and the explanation of the measures contained in this document.'« less

Technical Letter Report: Evaluation and Analysis of a Few International Periodic Safety Review Summary Reports

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

Chopra, Omesh K.; Diercks, Dwight R.; Ma, David Chia-Chiun

At the request of the United States (U.S.) government, the International Atomic Energy Agency (IAEA) assembled a team of 20 senior safety experts to review the regulatory framework for the safety of operating nuclear power plants in the United States. This review focused on the effectiveness of the regulatory functions implemented by the NRC and on its commitment to nuclear safety and continuous improvement. One suggestion resulting from that review was that the U.S. Nuclear Regulatory Commission (NRC) incorporate lessons learned from periodic safety reviews (PSRs) performed in other countries as an input to the NRC’s assessment processes. In themore » U.S., commercial nuclear power plants (NPPs) are granted an initial 40-year operating license, which may be renewed for additional 20-year periods, subject to complying with regulatory requirements. The NRC has established a framework through its inspection, and operational experience processes to ensure the safe operation of licensed nuclear facilities on an ongoing basis. In contrast, most other countries do not impose a specific time limit on the operating licenses for NPPs, they instead require that the utility operating the plant perform PSRs, typically at approximately 10-year intervals, to assure continued safe operation until the next assessment. The staff contracted with Argonne National Laboratory (Argonne) to perform a pilot review of selected translated PSR assessment reports and related documentation from foreign nuclear regulatory authorities to identify any potential new regulatory insights regarding license renewal-related topics and NPP operating experience (OpE). A total of 14 PSR assessment documents from 9 countries were reviewed. For all of the countries except France, individual reports were provided for each of the plants reviewed. In the case of France, three reports were provided that reviewed the performance assessment of thirty-four 900-MWe reactors of similar design commissioned

International Scavenging for First Responder Guidance and Tools: IAEA Products

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

Stern, W.; Berthelot, L.; Bachner, K.

In fiscal years (FY) 2016 and 2017, with support from the U.S. Department of Homeland Security (DHS), Brookhaven National Laboratory (BNL) examined the International Atomic Energy Agency (IAEA) radiological emergency response and preparedness products (guidance and tools) to determine which of these products could be useful to U.S. first responders. The IAEA Incident and Emergency Centre (IEC), which is responsible for emergency preparedness and response, offers a range of tools and guidance documents for responders in recognizing, responding to, and recovering from radiation emergencies and incidents. In order to implement this project, BNL obtained all potentially relevant tools and productsmore » produced by the IAEA IEC and analyzed these materials to determine their relevance to first responders in the U.S. Subsequently, BNL organized and hosted a workshop at DHS National Urban Security Technology Laboratory (NUSTL) for U.S. first responders to examine and evaluate IAEA products to consider their applicability to the United States. This report documents and describes the First Responder Product Evaluation Workshop, and provides recommendations on potential steps the U.S. federal government could take to make IAEA guidance and tools useful to U.S. responders.« less

Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?

PubMed

Alqahtani, Saad; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Eguale, Tewodros

2015-07-01

The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA. This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999-2011. Descriptive statistics, t-tests, and chi-squared and Wilcoxon tests were performed. Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies. Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products. Copyright © 2015 John Wiley & Sons, Ltd.

Regulatory challenges in the review of data from global clinical trials: the PMDA perspective.

PubMed

Asano, K; Tanaka, A; Sato, T; Uyama, Y

2013-08-01

Regulatory agencies face challenges in reviewing data from global clinical trials (GCTs) in the era of globalization of drug development. One major challenge is consideration of ethnic factors in evaluating GCT data so as to extrapolate foreign population data to one's own national population. Here, we present the Pharmaceuticals and Medical Devices Agency (PMDA) perspective in reviewing GCT data in new drug applications (NDAs) and discuss future challenges for new drug approval.

Towards a tactical nuclear weapons treaty? Is There a Role of IAEA Tools of Safeguards?

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

Saunders, Emily C.; Rowberry, Ariana N.; Fearey, Bryan L.

2012-07-12

In recent years, there is growing interest in formal negotiations on non-strategic or tactical nuclear weapons. With the negotiations of New START, there has been much speculation that a tactical nuclear weapons treaty should be included in the follow on to New START. This paper examines the current policy environment related to tactical weapons and some of the issues surrounding the definition of tactical nuclear weapons. We then map out the steps that would need to be taken in order to begin discussions on a tactical nuclear weapons treaty. These steps will review the potential role of the IAEA inmore » verification of a tactical nuclear weapons treaty. Specifically, does IAEA involvement in various arms control treaties serve as a useful roadmap on how to overcome some of the issues pertaining to a tactical nuclear weapons treaty?« less

Statistical challenges in a regulatory review of cardiovascular and CNS clinical trials.

PubMed

Hung, H M James; Wang, Sue-Jane; Yang, Peiling; Jin, Kun; Lawrence, John; Kordzakhia, George; Massie, Tristan

2016-01-01

There are several challenging statistical problems identified in the regulatory review of large cardiovascular (CV) clinical outcome trials and central nervous system (CNS) trials. The problems can be common or distinct due to disease characteristics and the differences in trial design elements such as endpoints, trial duration, and trial size. In schizophrenia trials, heavy missing data is a big problem. In Alzheimer trials, the endpoints for assessing symptoms and the endpoints for assessing disease progression are essentially the same; it is difficult to construct a good trial design to evaluate a test drug for its ability to slow the disease progression. In CV trials, reliance on a composite endpoint with low event rate makes the trial size so large that it is infeasible to study multiple doses necessary to find the right dose for study patients. These are just a few typical problems. In the past decade, adaptive designs were increasingly used in these disease areas and some challenges occur with respect to that use. Based on our review experiences, group sequential designs (GSDs) have borne many successful stories in CV trials and are also increasingly used for developing treatments targeting CNS diseases. There is also a growing trend of using more advanced unblinded adaptive designs for producing efficacy evidence. Many statistical challenges with these kinds of adaptive designs have been identified through our experiences with the review of regulatory applications and are shared in this article.

Progress in Norwegian-Russian Regulatory Cooperation in Management of the Nuclear Legacy

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

Sneve, M.K.; Shandala, N.K.; Smith, G.M.

2008-07-01

The Norwegian Radiation Protection Authority (NRPA) and the Federal Medical-Biological Agency (FMBA) of the Russian Federation have a collaboration programme which forms part of the Norwegian government's Plan of Action to improve radiation and nuclear safety in northwest Russia. The background to the NRPA-FMBA collaboration programme has been described in previous WM presentations. This paper presents the substantial progress made within that programme, describes ongoing progress within specific projects and sets out the value arising from wider involvement in the programme of other organisations such as NATO and the technical support derived from other national agencies such as the IAEA,more » and regulatory authorities from the USA, the UK and France. The main activities of the cooperation projects are concerned with the management of the nuclear legacy in northwest Russia, in particular the remediation of facilities, and related spent fuel and radioactive waste management, at the former Shore Technical Bases at Andreeva Bay and Gremikha Village. New regulatory guidance documents have been developed, necessary because of the special abnormal situation at these sites, now designated as Sites of Temporary Storage (STS), but also because of the transition from military to civilian regulatory supervision and the evolving regulatory system in the Russian Federation. The work has involved major technical inputs from the Russian Federation Institute of Biophysics, as well as review and advice on international recommendations and good practice in other countries provided by other technical support organisations. Projects on-going in 2007 are described which involve regulatory guidance on very Low-Level Waste management, specifically for the licensing and operation of new VLLW disposal facilities; optimisation of operational radiation protection, particularly in areas of high ambient radiation dose rate as are found in some parts of the STSs; determination of factors

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

RELAP5 posttest calculation of IAEA-SPE-4

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

Petelin, S.; Mavko, B.; Parzer, I.

The International Atomic Energy Agency`s Fourth Standard Problem Exercise (IAEA-SPE-4) was performed at the PMK-2 facility. The PMK-2 facility is designed to study processes following small- and medium-size breaks in the primary system and natural circulation in VVER-440 plants. The IAEA-SPE-4 experiment represents a cold-leg side small break, similar to the IAEA-SPE-2, with the exception of the high-pressure safety injection being unavailable, and the secondary side bleed and feed initiation. The break valve was located at the dead end of a vertical downcomer, which in fact simulates a break in the reactor vessel itself, and should be unlikely to happenmore » in a real nuclear power plant (NPP). Three different RELAP5 code versions were used for the transient simulation in order to assess the calculations with test results.« less

76 FR 31349 - Determination of Regulatory Review Period for Purposes of Patent Extension; ACTEMRA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... Administration (FDA) has determined the regulatory review period for ACTEMRA and is publishing this notice of... applications to the Director of Patents and Trademarks, Department of Commerce, for the extension of patents... actual amount of extension that the Director of Patents and Trademarks may award (for example, half the...

76 FR 15323 - Determination of Regulatory Review Period for Purposes of Patent Extension; ATRYN

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

... regulatory review period for ATRYN and is publishing this notice of that determination as required by law. FDA has made the determination because of the submission of an application to the Director of Patents... of extension that the Director of Patents and Trademarks may award (for example, half the testing...

77 FR 26017 - Determination of Regulatory Review Period for Purposes of Patent Extension; KALBITOR

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... Administration (FDA) has determined the regulatory review period for KALBITOR and is publishing this notice of... applications to the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent... actual amount of extension that the Director of Patents and Trademarks may award (for example, half the...

75 FR 75678 - Determination of Regulatory Review Period for Purposes of Patent Extension; STELARA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... Administration (FDA) has determined the regulatory review period for STELARA and is publishing this notice of... application to the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent... toward the actual amount of extension that the Director of Patents and Trademarks may award (for example...

75 FR 76739 - Determination of Regulatory Review Period for Purposes of Patent Extension; ILARIS

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-09

... regulatory review period for ILARIS and is publishing this notice of that determination as required by law. FDA has made the determination because of the submission of an application to the Director of Patents... of extension that the Director of Patents and Trademarks may award (for example, half the testing...

77 FR 20830 - Determination of Regulatory Review Period for Purposes of Patent Extension; VIIBRYD

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

...) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L. 100-670) generally provide that a..., animal drug product, medical device, food additive, or color additive) was subject to regulatory review... consists of two periods of time: A testing phase and an approval phase. For human drug products, the...

10 CFR 150.17a - Compliance with requirements of US/IAEA Safeguards Agreement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Compliance with requirements of US/IAEA Safeguards... Authority in Agreement States § 150.17a Compliance with requirements of US/IAEA Safeguards Agreement. (a... shall take other action as may be necessary to implement the US/IAEA Safeguards Agreement, as described...

10 CFR 150.17a - Compliance with requirements of US/IAEA Safeguards Agreement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Compliance with requirements of US/IAEA Safeguards... Authority in Agreement States § 150.17a Compliance with requirements of US/IAEA Safeguards Agreement. (a... shall take other action as may be necessary to implement the US/IAEA Safeguards Agreement, as described...

A Regulatory Framework for Nanotechnology

DTIC Science & Technology

informed by a map of the regulatory landscape of nanotechnology and a review of the regulatory frameworks for the aviation and biotechnology industries...aviation and biotechnology and maps the regulatory landscape in the United States by examining stakeholders, regulatory entities, and applicable legislation...state of nanotechnology if the limitations of technical expertise are addressed. This expertise can be provided by advisory committees of technical

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.

Systematic review regulatory principles of non-coding RNAs in cardiovascular diseases.

PubMed

Li, Yongsheng; Huo, Caiqin; Pan, Tao; Li, Lili; Jin, Xiyun; Lin, Xiaoyu; Chen, Juan; Zhang, Jinwen; Guo, Zheng; Xu, Juan; Li, Xia

2017-08-16

Cardiovascular diseases (CVDs) continue to be a major cause of morbidity and mortality, and non-coding RNAs (ncRNAs) play critical roles in CVDs. With the recent emergence of high-throughput technologies, including small RNA sequencing, investigations of CVDs have been transformed from candidate-based studies into genome-wide undertakings, and a number of ncRNAs in CVDs were discovered in various studies. A comprehensive review of these ncRNAs would be highly valuable for researchers to get a complete picture of the ncRNAs in CVD. To address these knowledge gaps and clinical needs, in this review, we first discussed dysregulated ncRNAs and their critical roles in cardiovascular development and related diseases. Moreover, we reviewed >28 561 published papers and documented the ncRNA-CVD association benchmarking data sets to summarize the principles of ncRNA regulation in CVDs. This data set included 13 249 curated relationships between 9503 ncRNAs and 139 CVDs in 12 species. Based on this comprehensive resource, we summarized the regulatory principles of dysregulated ncRNAs in CVDs, including the complex associations between ncRNA and CVDs, tissue specificity and ncRNA synergistic regulation. The highlighted principles are that CVD microRNAs (miRNAs) are highly expressed in heart tissue and that they play central roles in miRNA-miRNA functional synergistic network. In addition, CVD-related miRNAs are close to one another in the functional network, indicating the modular characteristic features of CVD miRNAs. We believe that the regulatory principles summarized here will further contribute to our understanding of ncRNA function and dysregulation mechanisms in CVDs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dosimetric inter-institutional comparison in European radiotherapy centres: Results of IAEA supported treatment planning system audit.

PubMed

Gershkevitsh, Eduard; Pesznyak, Csilla; Petrovic, Borislava; Grezdo, Joseph; Chelminski, Krzysztof; do Carmo Lopes, Maria; Izewska, Joanna; Van Dyk, Jacob

2014-05-01

One of the newer audit modalities operated by the International Atomic Energy Agency (IAEA) involves audits of treatment planning systems (TPS) in radiotherapy. The main focus of the audit is the dosimetry verification of the delivery of a radiation treatment plan for three-dimensional (3D) conformal radiotherapy using high energy photon beams. The audit has been carried out in eight European countries - Estonia, Hungary, Latvia, Lithuania, Serbia, Slovakia, Poland and Portugal. The corresponding results are presented. The TPS audit reviews the dosimetry, treatment planning and radiotherapy delivery processes using the 'end-to-end' approach, i.e. following the pathway similar to that of the patient, through imaging, treatment planning and dose delivery. The audit is implemented at the national level with IAEA assistance. The national counterparts conduct the TPS audit at local radiotherapy centres through on-site visits. TPS calculated doses are compared with ion chamber measurements performed in an anthropomorphic phantom for eight test cases per algorithm/beam. A set of pre-defined agreement criteria is used to analyse the performance of TPSs. TPS audit was carried out in 60 radiotherapy centres. In total, 190 data sets (combination of algorithm and beam quality) have been collected and reviewed. Dosimetry problems requiring interventions were discovered in about 10% of datasets. In addition, suboptimal beam modelling in TPSs was discovered in a number of cases. The TPS audit project using the IAEA methodology has verified the treatment planning system calculations for 3D conformal radiotherapy in a group of radiotherapy centres in Europe. It contributed to achieving better understanding of the performance of TPSs and helped to resolve issues related to imaging, dosimetry and treatment planning.

The Nature of Procrastination: A Meta-Analytic and Theoretical Review of Quintessential Self-Regulatory Failure

ERIC Educational Resources Information Center

Steel, Piers

2007-01-01

Procrastination is a prevalent and pernicious form of self-regulatory failure that is not entirely understood. Hence, the relevant conceptual, theoretical, and empirical work is reviewed, drawing upon correlational, experimental, and qualitative findings. A meta-analysis of procrastination's possible causes and effects, based on 691 correlations,…

77 FR 26016 - Determination of Regulatory Review Period for Purposes of Patent Extension; Alair Bronchial...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

...) has determined the regulatory review period for Alair Bronchial Thermoplasty System and is publishing... submission of an application to the Director of Patents and Trademarks, Department of Commerce, for the... may count toward the actual amount of extension that the Director of Patents and Trademarks may award...

Four Years of Practical Arrangements between IAEA and Moscow SIA 'Radon': Preliminary Results - 13061

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

Batyukhnova, O.G.; Karlina, O.K.; Neveikin, P.P.

The International Education Training Centre (IETC) at Moscow State Unitary Enterprise Scientific and Industrial Association 'Radon' (SIA 'Radon'), in co-operation with the International Atomic Energy Agency (IAEA), has developed expertise and provided training to waste management personnel for the last 15 years. Since 1997, the educational system of the enterprise with the support of the IAEA has acquired an international character: more than 470 experts from 35 countries- IAEA Member States completed the professional development. Training is conducted at various thematic courses or fellowships for individual programs and seminars on IAEA technical projects. In June 2008 a direct agreement (Practicalmore » Arrangements) was signed between SIA 'Radon' and the IAEA on cooperation in the field of development of new technologies, expert's advice to IAEA Member States, and, in particular, the training of personnel in the field of radioactive waste management (RWM), which opens up new perspectives for fruitful cooperation of industry professionals. The paper summarizes the current experience of the SIA 'Radon' in the organization and implementation of the IAEA sponsored training and others events and outlines some of strategic educational elements, which IETC will continue to pursue in the coming years. (authors)« less

75 FR 55332 - Determination of Regulatory Review Period for Purposes of Patent Extension; ULORIC

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

... extended for a period of up to 5 years so long as the patented item (human drug product, animal drug... periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins... the length of a regulatory review period for a human drug product will include all of the testing...

75 FR 53315 - Determination of Regulatory Review Period for Purposes of Patent Extension; ONGLYZA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... extended for a period of up to 5 years so long as the patented item (human drug product, animal drug... periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins... the length of a regulatory review period for a human drug product will include all of the testing...

75 FR 54344 - Determination of Regulatory Review Period for Purposes of Patent Extension; EFFIENT

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... extended for a period of up to 5 years so long as the patented item (human drug product, animal drug... periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins... the length of a regulatory review period for a human drug product will include all of the testing...

75 FR 55331 - Determination of Regulatory Review Period for Purposes of Patent Extension; SAPHRIS

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

... extended for a period of up to 5 years so long as the patented item (human drug product, animal drug... periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins... the length of a regulatory review period for a human drug product will include all of the testing...

75 FR 19407 - Determination of Regulatory Review Period for Purposes of Patent Extension; SAVELLA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... extended for a period of up to 5 years so long as the patented item (human drug product, animal drug... periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins... the length of a regulatory review period for a human drug product will include all of the testing...

75 FR 77878 - Determination of Regulatory Review Period for Purposes of Patent Extension; FREESTYLE NAVIGATOR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... determined the regulatory review period for FREESTYLE NAVIGATOR and is publishing this notice of that... the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent which... toward the actual amount of extension that the Director of Patents and Trademarks may award (half the...

78 FR 12330 - Determination of Regulatory Review Period for Purposes of Patent Extension; SAPIEN TRANSCATHETER...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L. 100-670) generally provide that a..., animal drug product, medical device, food additive, or color additive) was subject to regulatory review... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-E-0196...

Fault displacement hazard assessment for nuclear installations based on IAEA safety standards

NASA Astrophysics Data System (ADS)

Fukushima, Y.

2016-12-01

In the IAEA Safety NS-R-3, surface fault displacement hazard assessment (FDHA) is required for the siting of nuclear installations. If any capable faults exist in the candidate site, IAEA recommends the consideration of alternative sites. However, due to the progress in palaeoseismological investigations, capable faults may be found in existing site. In such a case, IAEA recommends to evaluate the safety using probabilistic FDHA (PFDHA), which is an empirical approach based on still quite limited database. Therefore a basic and crucial improvement is to increase the database. In 2015, IAEA produced a TecDoc-1767 on Palaeoseismology as a reference for the identification of capable faults. Another IAEA Safety Report 85 on ground motion simulation based on fault rupture modelling provides an annex introducing recent PFDHAs and fault displacement simulation methodologies. The IAEA expanded the project of FDHA for the probabilistic approach and the physics based fault rupture modelling. The first approach needs a refinement of the empirical methods by building a world wide database, and the second approach needs to shift from kinematic to the dynamic scheme. Both approaches can complement each other, since simulated displacement can fill the gap of a sparse database and geological observations can be useful to calibrate the simulations. The IAEA already supported a workshop in October 2015 to discuss the existing databases with the aim of creating a common worldwide database. A consensus of a unified database was reached. The next milestone is to fill the database with as many fault rupture data sets as possible. Another IAEA work group had a WS in November 2015 to discuss the state-of-the-art PFDHA as well as simulation methodologies. Two groups jointed a consultancy meeting in February 2016, shared information, identified issues, discussed goals and outputs, and scheduled future meetings. Now we may aim at coordinating activities for the whole FDHA tasks jointly.

75 FR 54152 - Determination of Regulatory Review Period for Purposes of Patent Extension; NEURX DIAPHRAGM...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... determined the regulatory review period for NEURX DIAPHRAGM PACING SYSTEM and is publishing this notice of... application to the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent... toward the actual amount of extension that the Director of Patents and Trademarks may award (half the...

Strengthening IAEA Safeguards for Research Reactors

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

Reid, Bruce D.; Anzelon, George A.; Budlong-Sylvester, Kory

During their December 10-11, 2013, workshop in Grenoble France, which focused on the history and future of safeguarding research reactors, the United States, France and the United Kingdom (UK) agreed to conduct a joint study exploring ways to strengthen the IAEA’s safeguards approach for declared research reactors. This decision was prompted by concerns about: 1) historical cases of non-compliance involving misuse (including the use of non-nuclear materials for production of neutron generators for weapons) and diversion that were discovered, in many cases, long after the violations took place and as part of broader pattern of undeclared activities in half amore » dozen countries; 2) the fact that, under the Safeguards Criteria, the IAEA inspects some reactors (e.g., those with power levels under 25 MWt) less than once per year; 3) the long-standing precedent of States using heavy water research reactors (HWRR) to produce plutonium for weapons programs; 4) the use of HEU fuel in some research reactors; and 5) various technical characteristics common to some types of research reactors that could provide an opportunity for potential proliferators to misuse the facility or divert material with low probability of detection by the IAEA. In some research reactors it is difficult to detect diversion or undeclared irradiation. In addition, infrastructure associated with research reactors could pose a safeguards challenge. To strengthen the effectiveness of safeguards at the State level, this paper advocates that the IAEA consider ways to focus additional attention and broaden its safeguards toolbox for research reactors. This increase in focus on the research reactors could begin with the recognition that the research reactor (of any size) could be a common path element on a large number of technically plausible pathways that must be considered when performing acquisition pathway analysis (APA) for developing a State Level Approach (SLA) and Annual Implementation Plan

Regulatory mechanisms for absenteeism in the health sector: a systematic review of strategies and their implementation

PubMed Central

Kisakye, Angela N; Tweheyo, Raymond; Ssengooba, Freddie; Pariyo, George W; Rutebemberwa, Elizeus; Kiwanuka, Suzanne N

2016-01-01

Background A systematic review was undertaken to identify regulatory mechanisms aimed at mitigating health care worker absenteeism, to describe where and how they have been implemented as well as their possible effects. The goal was to propose potential policy options for managing the problem of absenteeism among human resources for health in low- and middle-income countries. Mechanisms described in this review are at the local workplace and broader national policy level. Methods A comprehensive online search was conducted on EMBASE, CINAHL, PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE search terms. Retrieved studies were uploaded onto reference manager and screened by two independent reviewers. Only publications in English were included. Data were extracted and synthesized according to the objectives of the review. Results Twenty six of the 4,975 published articles retrieved were included. All were from high-income countries and covered all cadres of health workers. The regulatory mechanisms and possible effects include 1) organizational-level mechanisms being reported as effective in curbing absenteeism in low- and middle-income countries (LMICs); 2) prohibition of private sector activities in LMICs offering benefits but presenting a challenge for the government to monitor the health workforce; 3) contractual changes from temporary to fixed posts having been associated with no reduction in absenteeism and not being appropriate for LMICs; 4) multifaceted work interventions being implemented in most settings; 5) the possibility of using financial and incentive regulatory mechanisms in LMICs; 6) health intervention mechanisms reducing absenteeism when integrated with exercise programs; and 7) attendance by legislation during emergencies being criticized for violating human rights in the United States and not being effective in curbing absenteeism. Conclusion Most countries have applied multiple strategies to mitigate health care

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...

75 FR 54887 - Determination of Regulatory Review Period for Purposes of Patent Extension; REPEL-CV

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... regulatory review period for REPEL-CV and is publishing this notice of that determination as required by law. FDA has made the determination because of the submission of an application to the Director of Patents... extension that the Director of Patents and Trademarks may award (half the testing phase must be subtracted...

Training activities at FSUE 'RADON' and Lomonosov's Moscow state university under practical arrangements with IAEA

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

Batyukhnova, O.G.; Karlina, O.K.; Neveykin, P.P.

The International Education Training Centre (IETC) at Moscow Federal State Unitary Enterprise (FSUE) 'Radon', in co-operation with the International Atomic Energy Agency (IAEA), has developed expertise and provided training to waste management personnel for the last 15 years. Since 1997, the educational system of the enterprise with the support of the IAEA has acquired an international character: more than 470 experts from 35 countries - IAEA Member States completed the professional development. Training is conducted at various thematic courses or fellowships for individual programs and seminars on IAEA technical projects. In June 2008 a direct agreement (Practical Arrangements) has beenmore » signed between FSUE 'Radon' and the IAEA on cooperation in the field of development of new technologies, expert's advice to IAEA Member States, and, in particular, the training of personnel in the field of radioactive waste management (RWM), which opens up new perspectives for fruitful cooperation of industry professionals. A similar agreement - Practical Arrangements - has been signed between Lomonosov's MSU and the IAEA in 2012. In October 2012 a new IAEA two-weeks training course started at Lomonosov's MSU and FSUE 'Radon' in the framework of the Practical Agreements signed. Pre-disposal management of waste was the main topic of the courses. The paper summarizes the current experience of the FSUE 'Radon' in the organization and implementation of the IAEA sponsored training and others events and outlines some of strategic educational elements, which IETC will continue to pursue in the coming years. (authors)« less

Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

PubMed

Mulinari, Shai; Davis, Courtney

2017-11-09

Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and

Systematic review of qualitative literature on occupational health and safety legislation and regulatory enforcement planning and implementation.

PubMed

MacEachen, Ellen; Kosny, Agnieszka; Ståhl, Christian; O'Hagan, Fergal; Redgrift, Lisa; Sanford, Sarah; Carrasco, Christine; Tompa, Emile; Mahood, Quenby

2016-01-01

The ability of occupational health and safety (OHS) legislation and regulatory enforcement to prevent workplace injuries and illnesses is contingent on political, economic, and organizational conditions. This systematic review of qualitative research articles considers how OHS legislation and regulatory enforcement are planned and implemented. A comprehensive search of peer-reviewed, English-language articles published between 1990 and 2013 yielded 11 947 articles. We identified 34 qualitative articles as relevant, 18 of which passed our quality assessment and proceeded to meta-ethnographic synthesis. The synthesis yielded four main themes: OHS regulation formation, regulation challenges, inspector organization, and worker representation in OHS. It illuminates how OHS legislation can be based on normative suppositions about worker and employer behavior and shaped by economic and political resources of parties. It also shows how implementation of OHS legislation is affected by "general duty" law, agency coordination, resourcing of inspectorates, and ability of workers to participate in the system. The review identifies methodological gaps and identifies promising areas for further research in "grey" zones of legislation implementation.

International Conference on Advances in Radiation Oncology (ICARO): outcomes of an IAEA meeting.

PubMed

Salminen, Eeva K; Kiel, Krystyna; Ibbott, Geoffrey S; Joiner, Michael C; Rosenblatt, Eduardo; Zubizarreta, Eduardo; Wondergem, Jan; Meghzifene, Ahmed

2011-02-04

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other international organizations to assess advances in technologies in radiation oncology in the face of economic challenges that most countries confront. Participants submitted research contributions, which were reviewed by a scientific committee and presented via 46 lectures and 103 posters. There were 327 participants from 70 Member States as well as participants from industry and government. The ICARO meeting provided an independent forum for the interaction of participants from developed and developing countries on current and developing issues related to radiation oncology.

IAEA programs in empowering the nuclear medicine profession through online educational resources.

PubMed

Pascual, Thomas Nb; Dondi, Maurizio; Paez, Diana; Kashyap, Ravi; Nunez-Miller, Rodolfo

2013-05-01

The International Atomic Energy Agency's (IAEA) programme in human health aims to enhance the capabilities in Member States to address needs related to the prevention, diagnosis, and treatment of diseases through the application of nuclear techniques. It has the specific mission of fostering the application of nuclear medicine techniques as part of the clinical management of certain types of diseases. Attuned to the continuous evolution of this specialty as well as to the advancement and diversity of methods in delivering capacity building efforts in this digital age, the section of nuclear medicine of the IAEA has enhanced its program by incorporating online educational resources for nuclear medicine professionals into its repertoire of projects to further its commitment in addressing the needs of its Member States in the field of nuclear medicine. Through online educational resources such as the Human Health Campus website, e-learning modules, and scheduled interactive webinars, a validation of the commitment by the IAEA in addressing the needs of its Member States in the field of nuclear medicine is strengthened while utilizing the advanced internet and communications technology which is progressively becoming available worldwide. The Human Health Campus (www.humanhealth.iaea.org) is the online educational resources initiative of the Division of Human Health of the IAEA geared toward enhancing professional knowledge of health professionals in radiation medicine (nuclear medicine and diagnostic imaging, radiation oncology, and medical radiation physics), and nutrition. E-learning modules provide an interactive learning environment to its users while providing immediate feedback for each task accomplished. Webinars, unlike webcasts, offer the opportunity of enhanced interaction with the learners facilitated through slide shows where the presenter guides and engages the audience using video and live streaming. This paper explores the IAEA's available online

Professor Glyn O. Phillip's legacy within the IAEA programme on radiation and tissue banking.

PubMed

Morales Pedraza, Jorge

2017-08-19

Professor Phillips began his involvement in the implementation of this important IAEA programme, insisting that there were advantages to be gained by using the ionizing radiation technique to sterilize human and animal tissues, based on the IAEA experience gained in the sterilization of medical products. The outcome of the implementation of the IAEA programme on radiation and tissue banking demonstrated that Professor Phillips was right in his opinion.

Reducing the risks from radon indoors: an IAEA perspective.

PubMed

Boal, T; Colgan, P A

2014-07-01

The IAEA has a mandate to develop, in collaboration with other relevant international organisations, 'standards of safety for protection of health and minimisation of danger to life and property', and to provide for the application of these standards. The most recent edition of the International Basic Safety Standards includes, for the first time, requirements to protect the public from exposure due to radon indoors. As a result, the IAEA has already developed guidance material in line with accepted best international practice and an international programme to assist its Member States in identifying and addressing high radon concentrations in buildings is being prepared. This paper overviews the current situation around the world and summarises the management approach advocated by the IAEA. A number of important scientific and policy issues are identified and discussed from the point-of-view of how they may impact on national action plans and strategies. Finally, the assistance and support available through the Agency is described. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of Alternative Funding Mechanisms for the IAEA

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

Toomey, Christopher; Wyse, Evan T.; Kurzrok, Andrew J.

While the International Atomic Energy Agency (IAEA) has enjoyed substantial success and prestige in the international community, there is growing concern that global demographic trends, advances in technology and the trend towards austerity in Member State budgets will stretch the Agency’s resources to a point where it may no longer be possible to execute its multifaceted mission in its entirety. As part of an ongoing effort by the Next Generation Safeguards Initiative to evaluate the IAEA’s long-term budgetary concerns , this paper proposes a series of alternate funding mechanisms that have the potential to sustain the IAEA in the long-term,more » including endowment, charity, and fee-for-service funding models.« less

Coordinated Research Projects of the IAEA Atomic and Molecular Data Unit

NASA Astrophysics Data System (ADS)

Braams, B. J.; Chung, H.-K.

2011-05-01

The IAEA Atomic and Molecular Data Unit is dedicated to the provision of databases for atomic, molecular and plasma-material interaction (AM/PMI) data that are relevant for nuclear fusion research. IAEA Coordinated Research Projects (CRPs) are the principal mechanism by which the Unit encourages data evaluation and the production of new data. Ongoing and planned CRPs on AM/PMI data are briefly described here.

Radiation processing techniques in remediation of pollutants, and the role of the IAEA in supporting capacity building in developing countries

NASA Astrophysics Data System (ADS)

Haji-Saeid, S. Mohammad.; Sampa, M. H.; Safrany, A.; Sabharwal, S.; Ramamoorthy, N.

2012-08-01

Radiation treatment, or a combination of radiation with conventional biological-chemical-physical processes, can help in the remediation of contaminated surfaces and in combating industrial chemical effluents and air pollution. The use of ionizing radiation as a powerful tool for inactivation of microbes is a valuable option to address likely threats from biohazard contamination that could be introduced either deliberately or inadvertently into areas where the public are exposed to, as well as for treatment of volatile organic compounds and similar hazardous chemical agents is an emerging development in tackling harmful pollutants. The role of the IAEA has been crucial both in supporting the development of local capabilities as well as in fostering international cooperation due to the multidisciplinary expertise required for achieving sustainable benefits. The IAEA is implementing Coordinated Research Projects, (CRP) thematic topical reviews of issues and challenges involved, and Technical Cooperation (TC) assistance in establishing and maintaining infrastructure in the MS. This paper will give an insight into the above mentioned IAEA activities, with examples of successes achieved through CRPs, as well as challenges on the road for broader dissemination of radiation processing technology for environmental remediation.

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit

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

Levine, Aaron L

Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit presentation from the WPTO FY14-FY16 Peer Review. The toolkit is aimed at regulatory agencies, consultants, project developers, the public, and any other party interested in learning more about the hydropower regulatory process.

IAEA activities related to radiation biology and health effects of radiation.

PubMed

Wondergem, Jan; Rosenblatt, Eduardo

2012-03-01

The IAEA is involved in capacity building with regard to the radiobiological sciences in its member states through its technical cooperation programme. Research projects/programmes are normally carried out within the framework of coordinated research projects (CRPs). Under this programme, two CRPs have been approved which are relevant to nuclear/radiation accidents: (1) stem cell therapeutics to modify radiation-induced damage to normal tissue, and (2) strengthening biological dosimetry in IAEA member states.

17 CFR 201.421 - Commission consideration of determinations by self-regulatory organizations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... determinations by self-regulatory organizations. 201.421 Section 201.421 Commodity and Securities Exchanges... Commission Review § 201.421 Commission consideration of determinations by self-regulatory organizations. (a..., order review of any determination by a self-regulatory organization that could be subject to an...

17 CFR 201.421 - Commission consideration of determinations by self-regulatory organizations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... determinations by self-regulatory organizations. 201.421 Section 201.421 Commodity and Securities Exchanges... Commission Review § 201.421 Commission consideration of determinations by self-regulatory organizations. (a..., order review of any determination by a self-regulatory organization that could be subject to an...

17 CFR 201.421 - Commission consideration of determinations by self-regulatory organizations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... determinations by self-regulatory organizations. 201.421 Section 201.421 Commodity and Securities Exchanges... Commission Review § 201.421 Commission consideration of determinations by self-regulatory organizations. (a..., order review of any determination by a self-regulatory organization that could be subject to an...

17 CFR 201.421 - Commission consideration of determinations by self-regulatory organizations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... determinations by self-regulatory organizations. 201.421 Section 201.421 Commodity and Securities Exchanges... Commission Review § 201.421 Commission consideration of determinations by self-regulatory organizations. (a..., order review of any determination by a self-regulatory organization that could be subject to an...

17 CFR 201.421 - Commission consideration of determinations by self-regulatory organizations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... determinations by self-regulatory organizations. 201.421 Section 201.421 Commodity and Securities Exchanges... Commission Review § 201.421 Commission consideration of determinations by self-regulatory organizations. (a..., order review of any determination by a self-regulatory organization that could be subject to an...

The IAEA neutron coincidence counting (INCC) and the DEMING least-squares fitting programs

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

Krick, M.S.; Harker, W.C.; Rinard, P.M.

1998-12-01

Two computer programs are described: (1) the INCC (IAEA or International Neutron Coincidence Counting) program and (2) the DEMING curve-fitting program. The INCC program is an IAEA version of the Los Alamos NCC (Neutron Coincidence Counting) code. The DEMING program is an upgrade of earlier Windows{reg_sign} and DOS codes with the same name. The versions described are INCC 3.00 and DEMING 1.11. The INCC and DEMING codes provide inspectors with the software support needed to perform calibration and verification measurements with all of the neutron coincidence counting systems used in IAEA inspections for the nondestructive assay of plutonium and uranium.

Implementation of the Regulatory Authority Information System in Egypt

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

Carson, S.D.; Schetnan, R.; Hasan, A.

2006-07-01

As part of the implementation of a bar-code-based system to track radioactive sealed sources (RSS) in Egypt, the Regulatory Authority Information System Personal Digital Assistant (RAIS PDA) Application was developed to extend the functionality of the International Atomic Energy Agency's (IAEA's) RAIS database by allowing users to download RSS data from the database to a portable PDA equipped with a bar-code scanner. [1, 4] The system allows users in the field to verify radioactive sealed source data, gather radioactive sealed source audit information, and upload that data to the RAIS database. This paper describes the development of the RAIS PDAmore » Application, its features, and how it will be implemented in Egypt. (authors)« less

Training of interventional cardiologists in radiation protection--the IAEA's initiatives.

PubMed

Rehani, Madan M

2007-01-08

The International Atomic Energy Agency (IAEA) has initiated a major international initiative to train interventional cardiologists in radiation protection as a part of its International Action Plan on the radiological protection of patients. A simple programme of two days' training has been developed, covering possible and observed radiation effects among patients and staff, international standards, dose management techniques, examples of good and bad practice and examples indicating prevention of possible injuries as a result of good practice of radiation protection. The training material is freely available on CD from the IAEA. The IAEA has conducted two events in 2004 and 2005 and number of events are planned in 2006. The survey conducted among the cardiologists participating in these programmes indicates that over 80% of them were attending such a structured programme on radiation protection for the first time. As the magnitude of X-ray usage in cardiology grows to match that in interventional radiology, the standards of training on radiation effects, radiation physics and radiation protection in interventional cardiology should also match those in interventional radiology.

Regulatory Sunset and Review Act of 2013

THOMAS, 113th Congress

Rep. Hultgren, Randy [R-IL-14

2013-01-18

House - 02/28/2013 Referred to the Subcommittee on Regulatory Reform, Commercial And Antitrust Law. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

The U.S./IAEA Workshop on Software Sustainability for Safeguards Instrumentation

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

Pepper S. E.; .; Worrall, L.

2014-08-08

The U.S. National Nuclear Security Administration’s Next Generation Safeguards Initiative, the U.S. Department of State, and the International Atomic Energy Agency (IAEA) organized a a workshop on the subject of ”Software Sustainability for Safeguards Instrumentation.” The workshop was held at the Vienna International Centre in Vienna, Austria, May 6-8, 2014. The workshop participants included software and hardware experts from national laboratories, industry, government, and IAEA member states who were specially selected by the workshop organizers based on their experience with software that is developed for the control and operation of safeguards instrumentation. The workshop included presentations, to orient the participantsmore » to the IAEA Department of Safeguards software activities related to instrumentation data collection and processing, and case studies that were designed to inspire discussion of software development, use, maintenance, and upgrades in breakout sessions and to result in recommendations for effective software practices and management. This report summarizes the results of the workshop.« less

Contribution to fusion research from IAEA coordinated research projects and joint experiments

NASA Astrophysics Data System (ADS)

Gryaznevich, M.; Van Oost, G.; Stöckel, J.; Kamendje, R.; Kuteev, B. N.; Melnikov, A.; Popov, T.; Svoboda, V.; The IAEA CRP Teams

2015-10-01

The paper presents objectives and activities of IAEA Coordinated Research Projects ‘Conceptual development of steady-state compact fusion neutron sources’ and ‘Utilisation of a network of small magnetic confinement fusion devices for mainstream fusion research’. The background and main projects of the CRP on FNS are described in detail, as this is a new activity at IAEA. Recent activities of the second CRP, which continues activities of previous CRPs, are overviewed.

Analysis of historical delta values for IAEA/LANL NDA training courses

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

Geist, William; Santi, Peter; Swinhoe, Martyn

2009-01-01

The Los Alamos National Laboratory (LANL) supports the International Atomic Energy Agency (IAEA) by providing training for IAEA inspectors in neutron and gamma-ray Nondestructive Assay (NDA) of nuclear material. Since 1980, all new IAEA inspectors attend this two week course at LANL gaining hands-on experience in the application of NDA techniques, procedures and analysis to measure plutonium and uranium nuclear material standards with well known pedigrees. As part of the course the inspectors conduct an inventory verification exercise. This exercise provides inspectors the opportunity to test their abilities in performing verification measurements using the various NDA techniques. For an inspector,more » the verification of an item is nominally based on whether the measured assay value agrees with the declared value to within three times the historical delta value. The historical delta value represents the average difference between measured and declared values from previous measurements taken on similar material with the same measurement technology. If the measurement falls outside a limit of three times the historical delta value, the declaration is not verified. This paper uses measurement data from five years of IAEA courses to calculate a historical delta for five non-destructive assay methods: Gamma-ray Enrichment, Gamma-ray Plutonium Isotopics, Passive Neutron Coincidence Counting, Active Neutron Coincidence Counting and the Neutron Coincidence Collar. These historical deltas provide information as to the precision and accuracy of these measurement techniques under realistic conditions.« less

INF and IAEA: A comparative analysis of verification strategy

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

Scheinman, L.; Kratzer, M.

1992-07-01

This is the final report of a study on the relevance and possible lessons of Intermediate Range Nuclear Force (INF) verification to the International Atomic Energy Agency (IAEA) international safeguards activities.

Deciphering the transcriptional cis-regulatory code.

PubMed

Yáñez-Cuna, J Omar; Kvon, Evgeny Z; Stark, Alexander

2013-01-01

Information about developmental gene expression resides in defined regulatory elements, called enhancers, in the non-coding part of the genome. Although cells reliably utilize enhancers to orchestrate gene expression, a cis-regulatory code that would allow their interpretation has remained one of the greatest challenges of modern biology. In this review, we summarize studies from the past three decades that describe progress towards revealing the properties of enhancers and discuss how recent approaches are providing unprecedented insights into regulatory elements in animal genomes. Over the next years, we believe that the functional characterization of regulatory sequences in entire genomes, combined with recent computational methods, will provide a comprehensive view of genomic regulatory elements and their building blocks and will enable researchers to begin to understand the sequence basis of the cis-regulatory code. Copyright © 2012 Elsevier Ltd. All rights reserved.

T regulatory cells in contact hypersensitivity.

PubMed

Cavani, Andrea

2008-08-01

The review summarizes the recent investigations focused on T regulatory cells in hapten diseases. Multiple mechanisms ensure tolerance to small chemicals penetrating the skin. Among these, specific T regulatory cells play a major role in controlling harmful immune responses to environmental antigens. Most of the T regulatory cells involved in this process belongs to the CD4 subset and suppress hapten-specific immune response through the release of IL-10 and through direct interaction with effector T cells, blocking their function. Methods for in-vitro and in-vivo expansion of specific T regulatory cells may represent an innovative approach for the cure of contact hypersensitivity.

Using Deep Learning Algorithm to Enhance Image-review Software for Surveillance Cameras

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

Cui, Yonggang; Thomas, Maikael A.

We propose the development of proven deep learning algorithms to flag objects and events of interest in Next Generation Surveillance System (NGSS) surveillance to make IAEA image review more efficient. Video surveillance is one of the core monitoring technologies used by the IAEA Department of Safeguards when implementing safeguards at nuclear facilities worldwide. The current image review software GARS has limited automated functions, such as scene-change detection, black image detection and missing scene analysis, but struggles with highly cluttered backgrounds. A cutting-edge algorithm to be developed in this project will enable efficient and effective searches in images and video streamsmore » by identifying and tracking safeguards relevant objects and detect anomalies in their vicinity. In this project, we will develop the algorithm, test it with the IAEA surveillance cameras and data sets collected at simulated nuclear facilities at BNL and SNL, and implement it in a software program for potential integration into the IAEA’s IRAP (Integrated Review and Analysis Program).« less

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...

77 FR 28467 - Identifying and Reducing Regulatory Burdens

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... online wherever practicable. Sec. 3. Setting Priorities. In implementing and improving their... regulatory priorities, to promote public participation in retrospective review, to modernize our regulatory..., agencies shall give priority, consistent with law, to those initiatives that will produce significant...

The relationship between time perspective and self-regulatory processes, abilities and outcomes: a protocol for a meta-analytical review

PubMed Central

Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M

2017-01-01

Introduction Both theoretical and empirical evidence suggests that time perspective is likely to influence self-regulatory processes and outcomes. Despite the theoretical and practical significance of such relations, the relationship between time perspective and self-regulatory processes and outcomes across different measures, samples and life domains, including health, has yet to be explored. Methods and analysis The proposed review will develop a taxonomy for classifying measures according to the self-regulatory process, ability or outcome that they are likely to reflect. Electronic scientific databases will be searched, along with relevant conference abstract booklets and citation lists. Additionally, a call for unpublished data will be submitted to relevant bodies. To be eligible for inclusion, studies must include a measure of time perspective and a measure of at least one self-regulatory process, ability and/ or outcome. Eligibility will not be restricted by publication date, language, type of sample or setting. The bivariate correlations will be extracted (or calculated) and submitted to a random-effects meta-analysis. The sample-weighted average effect size, heterogeneity, risk of bias and publication bias will be calculated, and the effects of categorical and continuous moderator variables on the effect sizes will be determined. Ethics and dissemination The proposed meta-analysis will synthesise previously conducted research; thus, ethical approval is not required. The findings will be submitted for publication in an international peer-reviewed journal and reported as part of the first author’s PhD thesis. The findings will also be disseminated to the research community and, where appropriate, to other interested parties through presentations at relevant academic and non-academic conferences. PMID:28679677

A method for independent modelling in support of regulatory review of dose assessments.

PubMed

Dverstorp, Björn; Xu, Shulan

2017-11-01

Several countries consider geological disposal facilities as the preferred option for spent nuclear fuel due to their potential to provide isolation from the surface environment on very long timescales. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a spent nuclear fuel repository. The disposal method involves disposing spent fuel in copper canisters with a cast iron insert at about 500 m depth in crystalline basement rock, and each canister is surrounded by a buffer of swelling bentonite clay. SKB's license application is supported by a post-closure safety assessment, SR-Site. SR-Site has been reviewed by the Swedish Radiation Safety Authority (SSM) for five years. The main method for review of SKB's license application is document review, which is carried out by SSM's staff and supported by SSM's external experts. The review has proven a challenging task due to its broad scope, complexity and multidisciplinary nature. SSM and its predecessors have, for several decades, been developing independent models to support regulatory reviews of post-closure safety assessments for geological repositories. For the review of SR-Site, SSM has developed a modelling approach with a structured application of independent modelling activities, including replication modelling, use of alternative conceptual models and bounding calculations, to complement the traditional document review. This paper describes this scheme and its application to biosphere and dose assessment modelling. SSM's independent modelling has provided important insights regarding quality and reasonableness of SKB's rather complex biosphere modelling and has helped quantifying conservatisms and highlighting conceptual uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

IAEA Nuclear Data Section: provision of atomic and nuclear databases for user applications.

PubMed

Humbert, Denis P; Nichols, Alan L; Schwerer, Otto

2004-01-01

The Nuclear Data Section (NDS) of the International Atomic Energy Agency (IAEA) provides a wide range of atomic and nuclear data services to scientists worldwide, with particular emphasis placed on the needs of developing countries. Highly focused Co-ordinated Research Projects and multinational data networks are sponsored under the auspices of the IAEA for the development and assembly of databases through the organised participation of specialists from Member States. More than 100 data libraries are readily available cost-free through the Internet, CD-ROM and other media. These databases are used in a wide range of applications, including fission- and fusion-energy, non-energy applications and basic research studies. Further information concerning the various services can be found through the web address of the IAEA Nuclear Data Section: and a mirror site at IPEN, Brazil that is maintained by NDS staff:.

Calibrated sulfur isotope abundance ratios of three IAEA sulfur isotope reference materials and V-CDT with a reassessment of the atomic weight of sulfur

NASA Astrophysics Data System (ADS)

Ding, T.; Valkiers, S.; Kipphardt, H.; De Bièvre, P.; Taylor, P. D. P.; Gonfiantini, R.; Krouse, R.

2001-08-01

Calibrated values have been obtained for sulfur isotope abundance ratios of sulfur isotope reference materials distributed by the IAEA (Vienna). For the calibration of the measurements, a set of synthetic isotope mixtures were prepared gravimetrically from high purity Ag2S materials enriched in32S, 33S, and 34S. All materials were converted into SF6 gas and subsequently, their sulfur isotope ratios were measured on the SF5+ species using a special gas source mass spectrometer equipped with a molecular flow inlet system (IRMM's Avogadro II amount comparator). Values for the 32S/34S abundance ratios are 22.650 4(20), 22.142 4(20), and 23.393 3(17) for IAEA-S-1, IAEA-S-2, and IAEA-S-3, respectively. The calculated 32S/34S abundance ratio for V-CDT is 22.643 6(20), which is very close to the calibrated ratio obtained by Ding et al. (1999). In this way, the zero point of the VCDT scale is anchored firmly to the international system of units SI. The 32S/33S abundance ratios are 126.942(47), 125.473(55), 129.072(32), and 126.948(47) for IAEA-S-1, IAEA-S-2, IAEA-S-3, and V-CDT, respectively. In this way, the linearity of the V-CDT scale is improved over this range. The values of the sulfur molar mass for IAEA-S-1 and V-CDT were calculated to be 32.063 877(56) and 32.063 911(56), respectively, the values with the smallest combined uncertainty ever reported for the sulfur molar masses (atomic weights).

What's the Regulatory Value of a Target Product Profile?

PubMed

Breder, Christopher D; Du, Wenny; Tyndall, Adria

2017-07-01

Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

Proficiency Testing as a tool to monitor consistency of measurements in the IAEA/WHO Network of Secondary Standards Dosimetry Laboratories

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

Meghzifene, Ahmed; Czap, Ladislav; Shortt, Ken

2008-08-14

The International Atomic Energy Agency (IAEA) and the World Health Organization (WHO) established a Network of Secondary Standards Dosimetry Laboratories (IAEA/WHO SSDL Network) in 1976. Through SSDLs designated by Member States, the Network provides a direct link of national dosimetry standards to the international measurement system of standards traceable to the Bureau International des Poids et Mesures (BIPM). Within this structure and through the proper calibration of field instruments, the SSDLs disseminate S.I. quantities and units.To ensure that the services provided by SSDL members to end-users follow internationally accepted standards, the IAEA has set up two different comparison programmes. Onemore » programme relies on the IAEA/WHO postal TLD service and the other uses comparisons of calibrated ionization chambers to help the SSDLs verify the integrity of their national standards and the procedures used for the transfer of the standards to the end-users. The IAEA comparisons include {sup 60}Co air kerma (N{sub K}) and absorbed dose to water (N{sub D,W}) coefficients. The results of the comparisons are confidential and are communicated only to the participants. This is to encourage participation of the laboratories and their full cooperation in the reconciliation of any discrepancy.This work describes the results of the IAEA programme comparing calibration coefficients for radiotherapy dosimetry, using ionization chambers. In this programme, ionization chambers that belong to the SSDLs are calibrated sequentially at the SSDL, at the IAEA, and again at the SSDL. As part of its own quality assurance programme, the IAEA has participated in several regional comparisons organized by Regional Metrology Organizations.The results of the IAEA comparison programme show that the majority of SSDLs are capable of providing calibrations that fall inside the acceptance level of 1.5% compared to the IAEA.« less

The relationship between time perspective and self-regulatory processes, abilities and outcomes: a protocol for a meta-analytical review.

PubMed

Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M

2017-07-05

Both theoretical and empirical evidence suggests that time perspective is likely to influence self-regulatory processes and outcomes. Despite the theoretical and practical significance of such relations, the relationship between time perspective and self-regulatory processes and outcomes across different measures, samples and life domains, including health, has yet to be explored. The proposed review will develop a taxonomy for classifying measures according to the self-regulatory process, ability or outcome that they are likely to reflect. Electronic scientific databases will be searched, along with relevant conference abstract booklets and citation lists. Additionally, a call for unpublished data will be submitted to relevant bodies. To be eligible for inclusion, studies must include a measure of time perspective and a measure of at least one self-regulatory process, ability and/ or outcome. Eligibility will not be restricted by publication date, language, type of sample or setting. The bivariate correlations will be extracted (or calculated) and submitted to a random-effects meta-analysis. The sample-weighted average effect size, heterogeneity, risk of bias and publication bias will be calculated, and the effects of categorical and continuous moderator variables on the effect sizes will be determined. The proposed meta-analysis will synthesise previously conducted research; thus, ethical approval is not required. The findings will be submitted for publication in an international peer-reviewed journal and reported as part of the first author’s PhD thesis. The findings will also be disseminated to the research community and, where appropriate, to other interested parties through presentations at relevant academic and non-academic conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

IAEA Co-ordinated Research Project: update of X-ray and gamma-ray decay data standards for detector calibration and other applications.

PubMed

Nichols, Alan L

2004-01-01

A Co-ordinated Research Project (CRP) was established in 1998 by the IAEA Nuclear Data Section (Update of X-ray and gamma-ray Decay Data Standards for Detector Calibration and Other Applications), in order to improve further the recommended decay data used to undertake efficiency calibrations of gamma-ray detectors. Participants in this CRP reviewed and modified the list of radionuclides most suited for detector efficiency calibration, and also considered the decay-data needs for safeguards, waste management, dosimetry, nuclear medicine, material analysis and environmental monitoring. Overall, 62 radionuclides were selected for decay-data evaluation, along with four parent-daughter combinations and two natural decay chains. gamma-ray emissions from specific nuclear reactions were also included to extend the calibrant energy well beyond 10 MeV. A significant number of these decay-data evaluations have been completed, and an IAEA-TECDOC report and database are in the process of being assembled for planned completion by the end of 2003.

The 1998 Australian external beam radiotherapy survey and IAEA/WHO TLD postal dose quality audit.

PubMed

Huntley, R; Izewska, J

2000-03-01

The results of an updated Australian survey of external beam radiotherapy centres are presented. Most of the centres provided most of the requested information. The relative caseloads of various linear accelerator photon and electron beams have not changed significantly since the previous survey in 1995. The mean age of Australian LINACs is 7.1 years and that of other radiotherapy machines is 14.7 years. Every Australian radiotherapy centre participated in a special run of the IAEA/WHO TLD postal dose quality audit program, which was provided for Australian centres by the IAEA and WHO in May 1998. The dose quoted by the centres was in nearly every case within 1.5% of the dose assessed by the IAEA. This is within the combined standard uncertainty of the IAEA TLD service (1.8%). The results confirm the accuracy and precision of radiotherapy dosimetry in Australia and the adequate dissemination of the Australian standards from ARL (now ARPANSA) to the centres. The Australian standards have recently been shown to agree with those of other countries to within 0.25% by comparison with the BIPM.

The US Support Program to IAEA Safeguards Priority of Training and Human Resources

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

Queirolo,A.

2008-06-13

The U.S. Support Program to IAEA Safeguards (USSP) priority of training and human resources is aimed at providing the Department of Safeguards with an appropriate mixture of regular staff and extrabudgetary experts who are qualified to meet the IAEA's technical needs and to provide personnel with appropriate instruction to improve the technical basis and specific skills needed to perform their job functions. The equipment and methods used in inspection activities are unique, complex, and evolving. New and experienced safeguards inspectors need timely and effective training to perform required tasks and to learn new skills prescribed by new safeguards policies ormore » agreements. The role of the inspector has changed from that of strictly an accountant to include that of a detective. New safeguards procedures are being instituted, and therefore, experienced inspectors must be educated on these new procedures. The USSP also recognizes the need for training safeguards support staff, particularly those who maintain and service safeguards equipment (SGTS), and those who perform information collection and analysis (SGIM). The USSP is committed to supporting the IAEA with training to ensure the effectiveness of all staff members and will continue to offer its assistance in the development and delivery of basic, refresher, and advanced training courses. This paper will discuss the USSP ongoing support in the area of training and IAEA staffing.« less

IAEA activities in the area of partitioning and transmutation

NASA Astrophysics Data System (ADS)

Stanculescu, Alexander

2006-06-01

Four major challenges are facing the long-term development of nuclear energy: improvement of the economic competitiveness, meeting increasingly stringent safety requirements, adhering to the criteria of sustainable development, and public acceptance. Meeting the sustainability criteria is the driving force behind the topic of this paper. In this context, sustainability has two aspects: natural resources and waste management. IAEA's activities in the area of Partitioning and Transmutation (P&T) are mostly in response to the latter. While not involving the large quantities of gaseous products and toxic solid wastes associated with fossil fuels, radioactive waste disposal is today's dominant public acceptance issue. In fact, small waste quantities permit a rigorous confinement strategy, and mined geological disposal is the strategy followed by some countries. Nevertheless, political opposition arguing that this does not yet constitute a safe disposal technology has largely stalled these efforts. One of the primary reasons cited is the long life of many of the radioisotopes generated from fission. This concern has led to increased R&D efforts to develop a technology aimed at reducing the amount and radio-toxicity of long-lived radioactive waste through transmutation in fission reactors or sub-critical systems. In the frame of the Project on Technology Advances in Fast Reactors and Accelerator-Driven Systems (ADS), the IAEA initiated a number of activities on utilization of plutonium and transmutation of long-lived radioactive waste, ADS, and deuterium-tritium plasma-driven sub-critical systems. The paper presents past accomplishments, current status and planned activities of this IAEA project.

REFINE WETLAND REGULATORY PROGRAM

EPA Science Inventory

The Tribes will work toward refining a regulatory program by taking a draft wetland conservation code with permitting incorporated to TEB for review. Progress will then proceed in developing a permit tracking system that will track both Tribal and fee land sites within reservati...

MicroRNA-mediated regulatory circuits: outlook and perspectives

NASA Astrophysics Data System (ADS)

Cora', Davide; Re, Angela; Caselle, Michele; Bussolino, Federico

2017-08-01

MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role. This review provides a summarizing view of the state-of-the-art, and perspectives of research efforts on microRNA-mediated regulatory motifs. In this review, we discuss the topological properties characterizing different types of circuits, and the regulatory features theoretically enabled by such properties, with a special emphasis on examples of circuits typifying their biological significance in experimentally validated contexts. Finally, we will consider possible future developments, in particular regarding microRNA-mediated circuits involving long non-coding RNAs and epigenetic regulators.

Testing the validity of the International Atomic Energy Agency (IAEA) safety culture model.

PubMed

López de Castro, Borja; Gracia, Francisco J; Peiró, José M; Pietrantoni, Luca; Hernández, Ana

2013-11-01

This paper takes the first steps to empirically validate the widely used model of safety culture of the International Atomic Energy Agency (IAEA), composed of five dimensions, further specified by 37 attributes. To do so, three independent and complementary studies are presented. First, 290 students serve to collect evidence about the face validity of the model. Second, 48 experts in organizational behavior judge its content validity. And third, 468 workers in a Spanish nuclear power plant help to reveal how closely the theoretical five-dimensional model can be replicated. Our findings suggest that several attributes of the model may not be related to their corresponding dimensions. According to our results, a one-dimensional structure fits the data better than the five dimensions proposed by the IAEA. Moreover, the IAEA model, as it stands, seems to have rather moderate content validity and low face validity. Practical implications for researchers and practitioners are included. Copyright © 2013 Elsevier Ltd. All rights reserved.

Review on the worldwide regulatory framework for biosimilars focusing on the Mexican case as an emerging market in Latin America.

PubMed

Ibarra-Cabrera, Ricardo; Mena-Pérez, Sandra Carolina; Bondani-Guasti, Augusto; García-Arrazola, Roeb

2013-12-01

The global biopharmaceutical market is worth over $100 billion USD. Nearly 90% of these products will lose their patent in the next ten years, leading to the commercialization of their subsequent versions, known as 'biosimilars'. Biosimilars are much more complex molecules than chemically synthesized generics in terms of size, structure, stability, microheterogeneity, manufacture, etc. Therefore, a specific regulatory framework is needed in order to demonstrate their comparability with innovative products, as well as their quality, safety and efficacy. The EU published the first regulatory pathway in 2005 and has approved 14 biosimilars. Mexico has recently developed a clear regulatory pathway for these products. Their legal basis was established in Article 222 Bis of General Law of Health in 2009, clear specifications in the Regulation for Health Goods in 2011, and further requirements in the Mexican Official Norm NOM-EM-001-SSA1-2012. The aim of this review is to summarize the regulatory pathways for biosimilars in the world with a special focus on Mexican experience, so as contribute to the development of regulations in other countries. Copyright © 2013 Elsevier Inc. All rights reserved.

77 FR 7980 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

...The Regulatory Agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The Agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this Agenda.

75 FR 79811 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

...The regulatory agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this agenda.

75 FR 21839 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

...The regulatory agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this agenda.

Uncovering drug-responsive regulatory elements

PubMed Central

Luizon, Marcelo R; Ahituv, Nadav

2015-01-01

Nucleotide changes in gene regulatory elements can have a major effect on interindividual differences in drug response. For example, by reviewing all published pharmacogenomic genome-wide association studies, we show here that 96.4% of the associated single nucleotide polymorphisms reside in noncoding regions. We discuss how sequencing technologies are improving our ability to identify drug response-associated regulatory elements genome-wide and to annotate nucleotide variants within them. We highlight specific examples of how nucleotide changes in these elements can affect drug response and illustrate the techniques used to find them and functionally characterize them. Finally, we also discuss challenges in the field of drug-responsive regulatory elements that need to be considered in order to translate these findings into the clinic. PMID:26555224

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

TH-EF-204-02: Small Field Radiation Therapy: Physics and Recent Recommendations From IAEA and ICRU

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

Seuntjens, J.

Joanna E. Cygler, Jan Seuntjens, J. Daniel Bourland, M. Saiful Huq, Josep Puxeu Vaque, Daniel Zucca Aparicio, Tatiana Krylova, Yuri Kirpichev, Eric Ford, Caridad Borras Stereotactic Radiation Therapy (SRT) utilizes small static and dynamic (IMRT) fields, to successfully treat malignant and benign diseases using techniques such as Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT). SRT is characterized by sharp dose gradients for individual fields and their resultant dose distributions. For appropriate targets, small field radiotherapy offers improved treatment quality by allowing better sparing of organs at risk while delivering the prescribed target dose. Specialized small field treatment deliverymore » systems, such as robotic-controlled linear accelerators, gamma radiosurgery units, and dynamic arc linear accelerators may utilize rigid fixation, image guidance, and tumor tracking, to insure precise dose delivery to static or moving targets. However, in addition to great advantages, small field delivery techniques present special technical challenges for dose calibration due to unique geometries and small field sizes not covered by existing reference dosimetry protocols such as AAPM TG-51 or IAEA TRS 398. In recent years extensive research has been performed to understand small field dosimetry and measurement instrumentation. AAPM, IAEA and ICRU task groups are expected to provide soon recommendations on the dosimetry of small radiation fields. In this symposium we will: 1] discuss the physics, instrumentation, methodologies and challenges for small field radiation dose measurements; 2] review IAEA and ICRU recommendations on prescribing, recording and reporting of small field radiation therapy; 3] discuss selected clinical applications and technical aspects for specialized image-guided, small field, linear accelerator based treatment techniques such as IMRT and SBRT. Learning Objectives: To learn the physics of small fields in

Development of Risk Insights for Regulatory Review of a Near-Surface Disposal Facility for Radioactive Waste

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

Esh, D.W.; Ridge, A.C.; Thaggard, M.

2006-07-01

Section 3116 of the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005 (NDAA) requires the Department of Energy (DOE) to consult with the Nuclear Regulatory Commission (NRC) about non-High Level Waste (HLW) determinations. In its consultative role, NRC performs technical reviews of DOE's waste determinations but does not have regulatory authority over DOE's waste disposal activities. The safety of disposal is evaluated by comparing predicted disposal facility performance to the performance objectives specified in NRC regulations for the disposal of low-level waste (10 CFR Part 61 Subpart C). The performance objectives contain criteria for protection of themore » public, protection of inadvertent intruders, protection of workers, and stability of the disposal site after closure. The potential radiological dose to receptors typically is evaluated with a performance assessment (PA) model that simulates the release of radionuclides from the disposal site, transport of radionuclides through the environment, and exposure of potential receptors to residual contamination for thousands of years. This paper describes NRC's development and use of independent performance assessment modeling to facilitate review of DOE's non-HLW determination for the Saltstone Disposal Facility (SDF) at the Savannah River Site. NRC's review of the safety of near-surface disposal of radioactive waste at the SDF was facilitated and focused by risk insights developed with an independent PA model. The main components of NRC's performance assessment model are presented. The development of risk insights that allow the staff to focus review efforts on those areas that are most important to satisfying the performance objectives is discussed. Uncertainty analysis was performed of the full stochastic model using genetic variable selection algorithms. The results of the uncertainty analysis were then used to guide the development of simulations of other scenarios to understand the

The Mailbox Computer System for the IAEA verification experiment on HEU downlending at the Portsmouth Gaseous Diffusion Plant

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

Aronson, A.L.; Gordon, D.M.

IN APRIL 1996, THE UNITED STATES (US) ADDED THE PORTSMOUTH GASEOUS DIFFUSION PLANT TO THE LIST OF FACILITIES ELIGIBLE FOR THE APPLICATION OF INTERNATIONAL ATOMIC ENERGY AGENCY (IAEA) SAFEGUARDS. AT THAT TIME, THE US PROPOSED THAT THE IAEA CARRY OUT A ''VERIFICATION EXPERIMENT'' AT THE PLANT WITH RESPECT TO DOOWNBLENDING OF ABOUT 13 METRIC TONS OF HIGHLY ENRICHED URANIUM (HEU) IN THE FORM OF URANIUM HEXAFLUROIDE (UF6). DURING THE PERIOD DECEMBER 1997 THROUGH JULY 1998, THE IAEA CARRIED OUT THE REQUESTED VERIFICATION EXPERIMENT. THE VERIFICATION APPROACH USED FOR THIS EXPERIMENT INCLUDED, AMONG OTHER MEASURES, THE ENTRY OF PROCESS-OPERATIONAL DATA BYmore » THE FACILITY OPERATOR ON A NEAR-REAL-TIME BASIS INTO A ''MAILBOX'' COMPUTER LOCATED WITHIN A TAMPER-INDICATING ENCLOSURE SEALED BY THE IAEA.« less

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Brazil.

PubMed

Herson, Marisa Roma; Mathor, Monica Beatriz; Morales Pedraza, Jorge

2009-05-01

Until 2000, efforts into organising tissue banks in Brazil had not progressed far beyond small "in house" tissue storage repositories, usually annexed to Orthopaedic Surgery Services. Despite the professional entrepreneurship of those working as part time tissue bankers in such operations, best practices in tissue banking were not always followed due to the lack of regulatory standards, specialised training, adequate facilities and dedicated personnel. The Skin Bank of the Plastic Surgery Department of the Hospital das Clinicas of Sao Paulo, the single skin bank in Brazil, was not an exception. Since 1956, restricted and unpredictable amounts of skin allografts were stored under refrigeration for short periods under very limited quality controls. As in most "tissue banks" at that time in Brazil, medical and nursing staff worked on a volunteer and informal basis undergoing no specific training. IAEA supported the implementation of the tissue banking program in Brazil through the regional project RLA/7/009 "Quality system for the production of irradiated sterilised grafts" (1998-2000) and through two interregional projects INT/6/049 "Interregional Centre of Excellence in Tissue Banking", during the period 2002-2004 and INT/6/052 "Improving the Quality of Production and Uses of Radiation Sterilised Tissue Grafts", during the period 2002-2004. In 2001-2002, the first two years of operation of the HC-Tissue Bank, 53 skin transplants were carried out instead of the previous 4-5 a year. During this period, 75 individuals donated skin tissue, generating approximately 90,000 cm(2) of skin graft. The IAEA program were of great benefit to Brazilian tissue banking which has evolved from scattered make shift small operations to a well-established, high quality tissue banking scenario.

Regulatory system reform of occupational health and safety in China.

PubMed

Wu, Fenghong; Chi, Yan

2015-01-01

With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

INF and IAEA: A comparative analysis of verification strategy. [Final report

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

Scheinman, L.; Kratzer, M.

1992-07-01

This is the final report of a study on the relevance and possible lessons of Intermediate Range Nuclear Force (INF) verification to the International Atomic Energy Agency (IAEA) international safeguards activities.

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

Progress and status of the IAEA coordinated research project: production of Mo-99 using LEU fission or neutron activation

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

Goldman, Ira N.; Adelfang, Pablo; Ramamoorthy, Natesan

2008-07-15

Since late 2004, the IAEA has developed and implemented a Coordinated Research Project (CRP) to assist countries interested in initiating indigenous, small-scale production of Mo-99 to meet local nuclear medicine requirements. The objective of the CRP is to provide interested countries with access to non-proprietary technologies and methods to produce Mo-99 using LEU foil or LEU mini-plate targets, or for the utilization of n,gamma neutron activation, e.g. through the use of gel generators. The project has made further progress since the RERTR 2006 meeting, with a Technical Workshop on Operational Aspects of Mo99 Production held 28-30 November 2006 in Viennamore » and the Second Research Coordination Meeting held in Bucharest, Romania 16-20 April 2007. The paper describes activities carried out as noted above, and as well as the provision of LEU foils to a number of participants, and the progress by a number of groups in preparing for LEU target assembly and disassembly, irradiation, chemical processing, and waste management. The participants' progress in particular on thermal hydraulics computations required for using LEU targets is notable, as also the progress in gel generator plant operations in India and Kazakhstan. Poland has joined as a new research agreement holder and an application by Egypt to be a contract holder is undergoing internal review in the IAEA and is expected to be approved. The IAEA has also participated in several open meetings of the U.S. National Academy of Sciences Study on Producing Medical Radioisotopes without HEU, which will also be discussed in the paper. (author)« less

Regulatory system reform of occupational health and safety in China

PubMed Central

WU, Fenghong; CHI, Yan

2015-01-01

With the explosive economic growth and social development, China’s regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined. PMID:25843565

Training in Tbilisi nuclear facility provides new sampling perspectives for IAEA inspectors

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

Brim, Cornelia P.

2016-06-08

Office of Nonproliferation and Arms Control- (NPAC-) sponsored training in a “cold” nuclear facility in Tbilisi, Georgia provides International Atomic Energy Agency (IAEA) inspectors with a new perspective on environmental sampling strategies. Sponsored by the Nuclear Safeguards program under the NPAC, Pacific Northwest National Laboratory (PNNL) experts have been conducting an annual weeklong class for IAEA inspectors in a closed nuclear facility since 2011. The Andronikashvili Institute of Physics and the Republic of Georgia collaborate with PNNL to provide the training, and the U.S. Department of State, the U.S. Embassy in Tbilisi and the U.S. Mission to International Organizations inmore » Vienna provide logistical support.« less

IAEA activities on atomic, molecular and plasma-material interaction data for fusion

NASA Astrophysics Data System (ADS)

Braams, Bastiaan J.; Chung, Hyun-Kyung

2013-09-01

The IAEA Atomic and Molecular Data Unit (http://www-amdis.iaea.org/) aims to provide internationally evaluated and recommended data for atomic, molecular and plasma-material interaction (A+M+PMI) processes in fusion research. The Unit organizes technical meetings and coordinates an A+M Data Centre Network (DCN) and a Code Centre Network (CCN). In addition the Unit organizes Coordinated Research Projects (CRPs), for which the objectives are mixed between development of new data and evaluation and recommendation of existing data. In the area of A+M data we are placing new emphasis in our meeting schedule on data evaluation and especially on uncertainties in calculated cross section data and the propagation of uncertainties through structure data and fundamental cross sections to effective rate coefficients. Following a recent meeting of the CCN it is intended to use electron scattering on Be, Ne and N2 as exemplars for study of uncertainties and uncertainty propagation in calculated data; this will be discussed further at the presentation. Please see http://www-amdis.iaea.org/CRP/ for more on our active and planned CRPs, which are concerned with atomic processes in core and edge plasma and with plasma interaction with beryllium-based surfaces and with irradiated tungsten.

Flight training efforts would benefit from more flexible aviation regulatory structures.

PubMed

Bent, J

1996-10-01

Training and regulatory issues related to modern flight deck systems are reviewed. Philosophical differences in regulatory bodies in the United States and Europe are highlighted. Methods of changing regulations in Europe and the United States are discussed.

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements.

PubMed

Nixon, Annabel; Kerr, Cicely; Breheny, Katie; Wild, Diane

2013-03-11

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through

Regulatory T cells in human disease and their potential for therapeutic manipulation

PubMed Central

Taams, Leonie S; Palmer, Donald B; Akbar, Arne N; Robinson, Douglas S; Brown, Zarin; Hawrylowicz, Catherine M

2006-01-01

Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a recent meeting [Clinical Application of Regulatory T Cells, 7–8 April 2005, Horsham, UK, organized by the authors of this review, in collaboration with the British Society for Immunology and Novartis] evidence was discussed that certain human autoimmune, infectious and allergic diseases are associated with impaired regulatory T-cell function. In contrast, evidence from several human cancer studies and some infections indicates that regulatory T cells may impair the development of protective immunity. Importantly, certain therapies, both those that act non-specifically to reduce inflammation and antigen-specific immunotherapies, may induce or enhance regulatory T-cell function. The purpose of this review was to summarize current knowledge on regulatory T-cell function in human disease, and to assess critically how this can be tailored to suit the therapeutic manipulation of immunity. PMID:16630018

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel

PubMed Central

Fregni, F; Nitsche, MA; Loo, C.K.; Brunoni, AR; Marangolo, P; Leite, J; Carvalho, S; Bolognini, N; Caumo, W; Paik, NJ; Simis, M; Ueda, K; Ekhitari, H; Luu, P; Tucker, DM; Tyler, WJ; Brunelin, J; Datta, A; Juan, CH; Venkatasubramanian, G; Boggio, PS; Bikson, M

2014-01-01

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. PMID:25983531

Legislative and regulatory modernization for therapeutic products.

PubMed

Maher, Maurica

2010-01-01

This presentation is intended to show how the work coming from scientists, physicians, and other healthcare professionals is incorporated into the regulatory assessment of therapeutic products in Canada. One of the primary objectives within the regulatory environment is to provide information back to healthcare professionals and patients in order to help them make informed decisions. The current regulatory system for health products in Canada and why it needs modernization is addressed; a "lifecycle approach" to the regulation of health products is presented; the Food and Consumer Safety Action Plan and Bill C-51, a bill to amend the Food and Drugs Act is reviewed; and the challenges and opportunities for Canada and its fellow regulators are examined.

Validating dose rate calibration of radiotherapy photon beams through IAEA/WHO postal audit dosimetry service.

PubMed

Jangda, Abdul Qadir; Hussein, Sherali

2012-05-01

In external beam radiation therapy (EBRT), the quality assurance (QA) of the radiation beam is crucial to the accurate delivery of the prescribed dose to the patient. One of the dosimetric parameters that require monitoring is the beam output, specified as the dose rate on the central axis under reference conditions. The aim of this project was to validate dose rate calibration of megavoltage photon beams using the International Atomic Energy Agency (IAEA)/World Health Organisation (WHO) postal audit dosimetry service. Three photon beams were audited: a 6 MV beam from the low-energy linac and 6 and 18 MV beams from a dual high-energy linac. The agreement between our stated doses and the IAEA results was within 1% for the two 6 MV beams and within 2% for the 18 MV beam. The IAEA/WHO postal audit dosimetry service provides an independent verification of dose rate calibration protocol by an international facility.

Regulatory T cells in the control of host-microorganism interactions (*).

PubMed

Belkaid, Yasmine; Tarbell, Kristin

2009-01-01

Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.

Prospective Activities outlined for Regulatory Approval in Ghana Overview

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

Abrefah, R.G.; Odoi, H.C.; Mo, S.C.

The Ghana Research Reactor-1 (GHARR-1) is one of Chinese’s Miniature Neutron Source Reactor (MNSR) which was purchased under a tripartite agreement between Ghana, China and the IAEA. The reactor was installed in 1994 and has since been in operation without any incident. It has been used chiefly for Neutron Activation Analysis (NAA) and Training of students in the field of Nuclear Engineering. The GHARR-1 has been earmarked for the Conversion of Core from HEU to LEU which is in accordance with the GTRI program and other related and/or associated programs. Over the past few years the National Nuclear Research Institutemore » (NNRI), the Operating Organization of the Research Reactor for the Ghana Atomic Energy Commission (GAEC), has undertaken various tasks in order to implement the replacement of the reactor core. After completion, of the neutronic calculations, results showed that that an LEU fuel of 12.5% enrichment was desirable. However, recent developments have shown that an LEU fuel with 13% enrichment will be fabricated by the manufacturers, which is captured in a fuel specification document sent to NNRI by the CIAE. It is therefore imperative that all neutronic and thermal hydraulic calculation be done again to help acquire regulatory approval. Furthermore, the radiation exposure to personnel involved in the conversion must be estimated to help convince our regulators. This paper outlines the processes and activities that will enable us meet regulatory requirements.« less

Applying a Developmental Framework to the Self-Regulatory Difficulties of Young Children with Prenatal Alcohol Exposure: A Review.

PubMed

Reid, Natasha; Petrenko, Christie L M

2018-06-01

Prenatal alcohol exposure (PAE) can be associated with significant difficulties in self-regulatory abilities. As such, interventions have been developed that focus on improving varying aspects of self-regulation for this population. The application of a multilevel theoretical framework that describes the development of self-regulation during early childhood could further advance the field. First, this framework could assist in elucidating mechanisms in the trajectories of early adjustment problems in this population and, second, informing the development of more precise assessment and interventions for those affected by PAE. The aims of the current review were to provide an overview of the self-regulatory framework proposed by Calkins and colleagues (e.g., Calkins, 2007; Calkins and Fox, 2002); examine the self-regulatory difficulties that are commonly experienced during infancy (i.e., 0 to 2 years) and early childhood (i.e., 3 to 8 years) in children with PAE in the context of the developmental framework; and describe how the framework can inform the development of future assessment and intervention provision for young children with PAE. The application of a developmental framework, such as proposed by Calkins and colleagues, allows for a systematic and theoretically driven approach to assessment and intervention programs for young children with PAE. Copyright © 2018 by the Research Society on Alcoholism.

Drug Development for Pediatric Populations: Regulatory Aspects

PubMed Central

Zisowsky, Jochen; Krause, Andreas; Dingemanse, Jasper

2010-01-01

Pediatric aspects are nowadays integrated early in the development process of a new drug. The stronger enforcement to obtain pediatric information by the regulatory agencies in recent years resulted in an increased number of trials in children. Specific guidelines and requirements from, in particular, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) form the regulatory framework. This review summarizes the regulatory requirements and strategies for pediatric drug development from an industry perspective. It covers pediatric study planning and conduct, considerations for first dose in children, appropriate sampling strategies, and different methods for data generation and analysis to generate knowledge about the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug in children. The role of Modeling and Simulation (M&S) in pediatrics is highlighted—including the regulatory basis—and examples of the use of M&S are illustrated to support pediatric drug development. PMID:27721363

Regulatory Challenges for Cartilage Repair Technologies.

PubMed

McGowan, Kevin B; Stiegman, Glenn

2013-01-01

In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

Regulatory Challenges for Cartilage Repair Technologies

PubMed Central

Stiegman, Glenn

2013-01-01

In the United States, few Food and Drug Administration (FDA)–approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product’s attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible. PMID:26069647

Broadening the cancer and cognition landscape: The role of self-regulatory challenges

PubMed Central

Arndt, Jamie; Das, Enny; Schagen, Sanne B.; Reid-Arndt, Stephanie A.; Cameron, Linda D.; Ahles, Tim A.

2013-01-01

Objective The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Methods Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy-stereotypes and their points of convergence are briefly reviewed. Results A review and conceptual integration of relevant literatures suggests that coping with cancer can impair self-regulatory capacity, there is overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggest insights that can inform when and among whom cognitive deficits may most likely emerge. Conclusions Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. PMID:23839818

Deterring Nuclear Proliferation: The Importance of IAEA Safeguards: A TEXTBOOK

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

Rosenthal, M.D.; Fishbone, L.G.; Gallini, L.

2012-03-13

Nuclear terrorism and nuclear proliferation are among the most pressing challenges to international peace and security that we face today. Iran and Syria remain in non-compliance with the safeguards requirements of the NPT, and the nuclear ambitions of North Korea remain unchecked. Despite these challenges, the NPT remains a cornerstone of the nuclear non-proliferation regime, and the safeguards implemented by the International Atomic Energy Agency (IAEA) under the NPT play a critical role in deterring nuclear proliferation.How do they work? Where did they come from? And what is their future? This book answers these questions. Anyone studying the field ofmore » nuclear non-proliferation will benefit from reading this book, and for anyone entering the field, the book will enable them to get a running start. Part I describes the foundations of the international safeguards system: its origins in the 1930s - when new discoveries in physics made it clear immediately that nuclear energy held both peril and promise - through the entry into force in 1970 of the NPT, which codified the role of IAEA safeguards as a means to verify states NPT commitments not to acquire nuclear weapons. Part II describes the NPT safeguards system, which is based on a model safeguards agreement developed specifically for the NPT, The Structure and Content of Agreements between the Agency and States required in connection with the Treaty on the Non-Proliferation of Nuclear Weapons, which has been published by the IAEA as INFCIRC/153. Part III describes events, especially in South Africa, the DPRK, and Iraq in the early 1990s, that triggered a transformation in the way in which safeguards were conceptualized and implemented.« less

10 CFR 75.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Purpose. 75.1 Section 75.1 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT General Provisions... under these US/IAEA Safeguards treaties. These obligations include providing information to the IAEA on...

10 CFR 75.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Purpose. 75.1 Section 75.1 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT General Provisions... under these US/IAEA Safeguards treaties. These obligations include providing information to the IAEA on...

Radionuclide transfer to fruit in the IAEA TRS No. 472

NASA Astrophysics Data System (ADS)

Carini, F.; Pellizzoni, M.; Giosuè, S.

2012-04-01

This paper describes the approach taken to present the information on fruits in the IAEA report TRS No. 472, supported by the IAEA-TECDOC-1616, which describes the key transfer processes, concepts and conceptual models regarded as important for dose assessment, as well as relevant parameters for modelling radionuclide transfer in fruits. Information relate to fruit plants grown in agricultural ecosystems of temperate regions. The relative significance of each pathway after release of radionuclides depends upon the radionuclide, the kind of crop, the stage of plant development and the season at time of deposition. Fruit intended as a component of the human diet is borne by plants that are heterogeneous in habits, and morphological and physiological traits. Information on radionuclides in fruit systems has therefore been rationalised by characterising plants in three groups: woody trees, shrubs, and herbaceous plants. Parameter values have been collected from open literature, conference proceedings, institutional reports, books and international databases. Data on root uptake are reported as transfer factor values related to fresh weight, being consumption data for fruits usually given in fresh weight.

US regulatory system for genetically modified [genetically modified organism (GMO), rDNA or transgenic] crop cultivars.

PubMed

McHughen, Alan; Smyth, Stuart

2008-01-01

This paper reviews the history of the federal regulatory oversight of plant agricultural biotechnology in the USA, focusing on the scientific and political forces moulding the continually evolving regulatory structure in place today. Unlike most other jurisdictions, the USA decided to adapt pre-existing legislation to encompass products of biotechnology. In so doing, it established an overarching committee (Office of Science and Technology Policy) to study and distribute various regulatory responsibilities amongst relevant agencies: the Food and Drug Administration, Environmental Protection Agency and US Department of Agriculture. This paper reviews the history and procedures of each agency in the execution of its regulatory duties and investigates the advantages and disadvantages of the US regulatory strategy.

Steering healthcare service delivery: a regulatory perspective.

PubMed

Prakash, Gyan

2015-01-01

The purpose of this paper is to explore regulation in India's healthcare sector and makes recommendations needed for enhancing the healthcare service. The literature was reviewed to understand healthcare's regulatory context. To understand the current healthcare system, qualitative data were collected from state-level officials, public and private hospital staff. A patient survey was performed to assess service quality (QoS). Regulation plays a central role in driving healthcare QoS. India needs to strengthen market and institutional co-production based approaches for steering its healthcare in which delivery processes are complex and pose different challenges. This study assesses current healthcare regulation in an Indian state and presents a framework for studying and strengthening regulation. Agile regulation should be based on service delivery issues (pull approach) rather than monitoring and sanctions based regulatory environment (push approach). Healthcare pitfalls across the world seem to follow similar follies. India's complexity and experience is useful for emerging and developed economies. The author reviewed around 70 publications and synthesised them in healthcare regulatory contexts. Patient's perception of private providers could be a key input towards steering regulation. Identifying gaps across QoS dimensions would be useful in taking corrective measures.

Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

NOTE: Monte Carlo simulation of correction factors for IAEA TLD holders

NASA Astrophysics Data System (ADS)

Hultqvist, Martha; Fernández-Varea, José M.; Izewska, Joanna

2010-03-01

The IAEA standard thermoluminescent dosimeter (TLD) holder has been developed for the IAEA/WHO TLD postal dose program for audits of high-energy photon beams, and it is also employed by the ESTRO-QUALity assurance network (EQUAL) and several national TLD audit networks. Factors correcting for the influence of the holder on the TL signal under reference conditions have been calculated in the present work from Monte Carlo simulations with the PENELOPE code for 60Co γ-rays and 4, 6, 10, 15, 18 and 25 MV photon beams. The simulation results are around 0.2% smaller than measured factors reported in the literature, but well within the combined standard uncertainties. The present study supports the use of the experimentally obtained holder correction factors in the determination of the absorbed dose to water from the TL readings; the factors calculated by means of Monte Carlo simulations may be adopted for the cases where there are no measured data.

10 CFR 50.78 - Facility information and verification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Facility information and verification. 50.78 Section 50.78 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Us/iaea... International Atomic Energy Agency (IAEA) and take other action as necessary to implement the US/IAEA Safeguards...

10 CFR 50.78 - Facility information and verification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Facility information and verification. 50.78 Section 50.78 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF PRODUCTION AND UTILIZATION FACILITIES Us/iaea... International Atomic Energy Agency (IAEA) and take other action as necessary to implement the US/IAEA Safeguards...

Regulatory states in the developmental control of gene expression.

PubMed

Peter, Isabelle S

2017-09-01

A growing body of evidence shows that gene expression in multicellular organisms is controlled by the combinatorial function of multiple transcription factors. This indicates that not the individual transcription factors or signaling molecules, but the combination of expressed regulatory molecules, the regulatory state, should be viewed as the functional unit in gene regulation. Here, I discuss the concept of the regulatory state and its proposed role in the genome-wide control of gene expression. Recent analyses of regulatory gene expression in sea urchin embryos have been instrumental for solving the genomic control of cell fate specification in this system. Some of the approaches that were used to determine the expression of regulatory states during sea urchin embryogenesis are reviewed. Significant developmental changes in regulatory state expression leading to the distinct specification of cell fates are regulated by gene regulatory network circuits. How these regulatory state transitions are encoded in the genome is illuminated using the sea urchin endoderm-mesoderms cell fate decision circuit as an example. These observations highlight the importance of considering developmental gene regulation, and the function of individual transcription factors, in the context of regulatory states. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Regulatory Flexibility: An Individual Differences Perspective on Coping and Emotion Regulation.

PubMed

Bonanno, George A; Burton, Charles L

2013-11-01

People respond to stressful events in different ways, depending on the event and on the regulatory strategies they choose. Coping and emotion regulation theorists have proposed dynamic models in which these two factors, the person and the situation, interact over time to inform adaptation. In practice, however, researchers have tended to assume that particular regulatory strategies are consistently beneficial or maladaptive. We label this assumption the fallacy of uniform efficacy and contrast it with findings from a number of related literatures that have suggested the emergence of a broader but as yet poorly defined construct that we refer to as regulatory flexibility. In this review, we articulate this broader construct and define both its features and limitations. Specifically, we propose a heuristic individual differences framework and review research on three sequential components of flexibility for which propensities and abilities vary: sensitivity to context, availability of a diverse repertoire of regulatory strategies, and responsiveness to feedback. We consider the methodological limitations of research on each component, review questions that future research on flexibility might address, and consider how the components might relate to each other and to broader conceptualizations about stability and change across persons and situations. © The Author(s) 2013.

77 FR 7663 - Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

...The Regulatory Flexibility Act requires that agencies publish semiannual regulatory agendas in the Federal Register describing regulatory actions they are developing that may have a significant economic impact on a substantial number of small entities (5 U.S.C. 602). Executive Order 12866 ``Regulatory Planning and Review,'' signed September 30, 1993 (58 FR 51735), and Office of Management and Budget memoranda implementing section 4 of that Order establish minimum standards for agencies' agendas, including specific types of information for each entry. The Unified Agenda of Federal Regulatory and Deregulatory Actions (Unified Agenda) helps agencies fulfill these requirements. All Federal regulatory agencies have chosen to publish their regulatory agendas as part of the Unified Agenda. Editions of the Unified Agenda prior to fall 2007 were printed in their entirety in the Federal Register. Beginning with the fall 2007 edition, the Internet is the basic means for conveying regulatory agenda information to the maximum extent legally permissible. The complete Unified Agenda for fall 2011, which contains the regulatory agendas for 59 Federal agencies, is available to the public at http:// reginfo.gov. The fall 2011 Unified Agenda publication appearing in the Federal Register consists of agency regulatory flexibility agendas, in accordance with the publication requirements of the Regulatory Flexibility Act. Agency regulatory flexibility agendas contain only those Agenda entries for rules that are likely to have a significant economic impact on a substantial number of small entities and entries that have been selected for periodic review under section 610 of the Regulatory Flexibility Act.

Regulatory and quality considerations for continuous manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

[Regulatory science: modern trends in science and education for pharmaceutical products].

PubMed

Beregovykh, V V; Piatigorskaia, N V; Aladysheva, Zh I

2012-01-01

This article reviews modern trends in development of new instruments, standards and approaches to drugs safety, efficacy and quality assessment in USA and EU that can be called by unique term--"regulatory science" which is a new concept for Russian Federation. New education programs (curricula) developed by USA and EU universities within last 3 years are reviewed. These programs were designed in order to build workforce capable to utilize science approach for drug regulation. The principal mechanisms for financing research in regulatory science used by Food and Drug Administration are analyzed. There are no such science and relevant researches in Russian Federation despite the high demand as well as needs for the system for higher education and life-long learning education of specialists for regulatory affairs (or compliance).

Regulatory physiology discipline science plan

NASA Technical Reports Server (NTRS)

1991-01-01

The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

Broadening the cancer and cognition landscape: the role of self-regulatory challenges.

PubMed

Arndt, Jamie; Das, Enny; Schagen, Sanne B; Reid-Arndt, Stephanie A; Cameron, Linda D; Ahles, Tim A

2014-01-01

The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as one of the key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy stereotypes, and their points of convergence are briefly reviewed. A review and conceptual integration of relevant literatures suggest that coping with cancer can impair self-regulatory capacity. There is an overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggests insights that can inform when and among whom cognitive deficits may most likely emerge. Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. Copyright © 2013 John Wiley & Sons, Ltd.

Regulatory issues for computerized electrocardiographic devices.

PubMed

Muni, Neal I; Ho, Charles; Mallis, Elias

2004-01-01

Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a "clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper.

75 FR 21729 - Semiannual Regulatory Agenda, Spring 2010

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

...This agenda provides summary descriptions of significant and not significant regulations being developed in agencies of the U.S. Department of Agriculture (USDA) in conformance with Executive Order 12866 ``Regulatory Planning and Review.''

75 FR 1088 - Notice of Availability of a Memorandum of Understanding Between the Nuclear Regulatory Commission...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-08

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0578] Notice of Availability of a Memorandum of Understanding Between the Nuclear Regulatory Commission and the Bureau of Land Management AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Availability. FOR FURTHER INFORMATION CONTACT: Mr. Alan Bjornsen, Project Manager, Environmental Review Branch,...

Regulatory and Quality Considerations for Continuous Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Review of Technical Studies in the United States in Support of Burnup Credit Regulatory Guidance

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

Wagner, John C; Parks, Cecil V; Mueller, Don

2010-01-01

Taking credit for the reduction in reactivity associated with fuel depletion can enable more cost-effective, higher-density storage, transport, disposal, and reprocessing of spent nuclear fuel (SNF) while maintaining sufficient subcritical margin to establish an adequate safety basis. Consequently, there continues to be considerable interest in the United States (U.S.), as well as internationally, in the increased use of burnup credit in SNF operations, particularly related to storage, transport, and disposal of commercial SNF. This interest has motivated numerous technical studies related to the application of burnup credit, both domestically and internationally, as well as the design of SNF storage, transportmore » and disposal systems that rely on burnup credit for maintaining subcriticality. Responding to industry requests and needs, the U.S. Nuclear Regulatory Commission (NRC) initiated a burnup credit research program in 1999, with support from the Oak Ridge National Laboratory (ORNL), to develop regulatory guidance and the supporting technical bases for allowing and expanding the use of burnup credit in pressurized-water reactor SNF storage and transport applications. Although this NRC research program has not been continuous since its inception, considerable progress has been achieved in many key areas in terms of increased understanding of relevant phenomena and issues, availability of relevant information and data, and subsequently updated regulatory guidance for expanded use of burnup credit. This paper reviews technical studies performed by ORNL for the U.S. NRC burnup credit research program. Examples of topics include reactivity effects associated with reactor operating characteristics, fuel assembly characteristics, burnable absorbers, control rods, spatial burnup distributions, cooling time, and assembly misloading; methods and data for validation of isotopic composition predictions; methods and data for validation of criticality calculations; and

76 FR 57683 - Regulatory Review Schedule

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... included a review of: (a) Part 518--Self Regulation of Class II Gaming; (b) A Sole Proprietary Interest... public that it was conducting a review of its regulations promulgated to implement 25 U.S.C. 2701-2721 of... established a Tribal consultation schedule with a description of the regulation groups to be covered during...

Numerical modeling of the radionuclide water pathway with HYDRUS and comparison with the IAEA model of SR 44.

PubMed

Merk, Rainer

2012-02-01

This study depicts a theoretical experiment in which the radionuclide transport through the porous material of a landfill consisting of concrete rubble (e.g., from the decommissioning of nuclear power plants) and the subsequent migration through the vadose zone and aquifer to a model well is calculated by means of the software HYDRUS-1D (Simunek et al., 2008). The radionuclides originally contained within the rubble become dissolved due to leaching caused by infiltrated rainwater. The resulting well-water contamination (in Bq/L) is calculated numerically as a function of time and location and compared with the outcome of a simplified analytic model for the groundwater pathway published by the IAEA (2005). Identical model parameters are considered. The main objective of the present work is to evaluate the predictive capacity of the more simple IAEA model using HYDRUS-1D as a reference. For most of the radionuclides considered (e.g., ¹²⁹I, and ²³⁹Pu), results from applying the IAEA model were found to be comparable to results from the more elaborate HYDRUS modeling, provided the underlying parameter values are comparable. However, the IAEA model appears to underestimate the effects resulting from, for example, high nuclide mobility, short half-life, or short-term variations in the water infiltration. The present results indicate that the IAEA model is suited for screening calculations and general recommendation purposes. However, the analysis of a specific site should be accompanied by detailed HYDRUS computer simulations. In all models considered, the calculation outcome largely depends on the choice of the sorption parameter K(d). Copyright © 2011 Elsevier Ltd. All rights reserved.

10 CFR 13.5 - Review by the reviewing official.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Review by the reviewing official. 13.5 Section 13.5 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.5 Review by the reviewing official. (a) If, based on the report of the investigating official under § 13.4(b), the reviewing official determines...

10 CFR 13.5 - Review by the reviewing official.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Review by the reviewing official. 13.5 Section 13.5 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.5 Review by the reviewing official. (a) If, based on the report of the investigating official under § 13.4(b), the reviewing official determines...

Perspectives on Regulatory T Cell Therapies

PubMed Central

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

2009-01-01

Summary Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as Treg cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human Treg cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease. PMID:21076548

Current status of herbal product: Regulatory overview

PubMed Central

Sharma, Sanjay

2015-01-01

A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment. PMID:26681886

Current status of herbal product: Regulatory overview.

PubMed

Sharma, Sanjay

2015-01-01

A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment.

The evolution and impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Asia and the Pacific region.

PubMed

Morales Pedraza, Jorge; Phillips, Glyn O

2009-05-01

The Asia and the Pacific region was within the IAEA program on radiation and tissue banking, the most active region. Most of the tissue banks in the Asia and the Pacific region were developed during the late 1980s and 1990s. The initial number of tissue banks established or supported by the IAEA program in the framework of the RCA Agreement for Asia and the Pacific region was 18. At the end of 2006, the number of tissue banks participating, in one way or another in the IAEA program was 59. Since the beginning of the implementation of the IAEA program in Asia and the Pacific region 63,537 amnion and 44,282 bone allografts were produced and 57,683 amnion and 36,388 bone allografts were used. The main impact of the IAEA program in the region was the following: the establishment or consolidation of at least 59 tissue banks in 15 countries in the region (the IAEA supported directly 16 of these banks); the improvement on the quality and safety of tissues procured and produced in the region reaching international standards; the implementation of eight national projects, two regional projects and two interregional projects; the elaboration of International Standards, a Code of Practice and a Public Awareness Strategies and, the application of quality control and quality assurances programs in all participating tissue banks.

Co-ordination of the International Network of Nuclear Structure and Decay Data Evaluators; Summary Report of an IAEA Technical Meeting

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

Abriola, D.; Tuli, J.

The IAEA Nuclear Data Section convened the 18th meeting of the International Network of Nuclear Structure and Decay Data Evaluators at the IAEA Headquarters, Vienna, 23 to 27 March 2009. This meeting was attended by 22 scientists from 14 Member States, plus IAEA staff, concerned with the compilation, evaluation and dissemination of nuclear structure and decay data. A summary of the meeting, recommendations/conclusions, data centre reports, and various proposals considered, modified and agreed by the participants are contained within this document. The International Network of Nuclear Structure and Decay Data (NSDD) Evaluators holds biennial meetings under the auspices of themore » IAEA, and consists of evaluation groups and data service centres in several countries. This network has the objective of providing up-to-date nuclear structure and decay data for all known nuclides by evaluating all existing experimental data. Data resulting from this international evaluation collaboration is included in the Evaluated Nuclear Structure Data File (ENSDF) and published in the journals Nuclear Physics A and Nuclear Data Sheets (NDS).« less

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota.

PubMed

Sun, M; He, C; Cong, Y; Liu, Z

2015-09-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3(+) regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders.

Dynamics of Bacterial Gene Regulatory Networks.

PubMed

Shis, David L; Bennett, Matthew R; Igoshin, Oleg A

2018-05-20

The ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks. Our goal is to discuss the general principles that allow extrapolation from a few model bacteria to less understood microbes. We emphasize that, in addition to well-studied effects of network architecture, network dynamics are shaped by global pleiotropic effects and cell physiology.

cis-Regulatory Mutations Are a Genetic Cause of Human Limb Malformations

PubMed Central

VanderMeer, Julia E.; Ahituv, Nadav

2011-01-01

The underlying mutations that cause human limb malformations are often difficult to determine, particularly for limb malformations that occur as isolated traits. Evidence from a variety of studies shows that cis-regulatory mutations, specifically in enhancers, can lead to some of these isolated limb malformations. Here, we provide a review of human limb malformations that have been shown to be caused by enhancer mutations and propose that cis-regulatory mutations will continue to be identified as the cause of additional human malformations as our understanding of regulatory sequences improves. PMID:21509892

Portrait of Candida Species Biofilm Regulatory Network Genes.

PubMed

Araújo, Daniela; Henriques, Mariana; Silva, Sónia

2017-01-01

Most cases of candidiasis have been attributed to Candida albicans, but Candida glabrata, Candida parapsilosis and Candida tropicalis, designated as non-C. albicans Candida (NCAC), have been identified as frequent human pathogens. Moreover, Candida biofilms are an escalating clinical problem associated with significant rates of mortality. Biofilms have distinct developmental phases, including adhesion/colonisation, maturation and dispersal, controlled by complex regulatory networks. This review discusses recent advances regarding Candida species biofilm regulatory network genes, which are key components for candidiasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Biomedical applications of tissue engineering technology: regulatory issues.

PubMed

Hellman, K B

1995-01-01

Novel emerging technologies such as tissue engineering, which utilize the approaches of molecular and cell biology, biotechnology, as well as materials science and engineering, are being used in the development of a wide range of biomedical products developed by industries regulated by the U.S. Food and Drug Administration (FDA). The FDA's mission is to promote and protect the public health by ensuring the safety and effectiveness of pharmaceuticals and medical devices, including those manufactured by novel technology, as assessed by scientific principles and methods. Regulatory review is conducted on a product-by-product basis. To accomplish its mission over the wide range of products in its regulatory purview, the FDA has six centers, each staffed with the scientific and regulatory expertise to evaluate the products in the center's jurisdiction. Recent legislative and regulatory changes are designed to simplify and facilitate the administrative process for evaluating novel combination products emanating from such interdisciplinary technology as tissue engineering and to resolve questions of product regulatory jurisdiction. Under the new procedures, the FDA may designate a lead FDA center for product review based on the primary mode of action of the combination product, with additional center(s) designated to assist in the evaluation in a collaborative or consultative capacity. In addition, FDA centers have increased their cooperation and information sharing with regard to evolving interdisciplinary technology. The FDA InterCenter Tissue Engineering Initiative was established to develop information on intercenter efforts in the evaluation of tissue engineering applications and to identify areas for further consideration. The FDA InterCenter Tissue Engineering Working Group, comprised of staff from the Center for Biologies Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Center for Drug Evaluation and Research (CDER), and Center

Decoding the role of regulatory element polymorphisms in complex disease.

PubMed

Vockley, Christopher M; Barrera, Alejandro; Reddy, Timothy E

2017-04-01

Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment. Establishing causality between non-coding genetic variants, gene regulation, and disease has recently become more feasible with advances in genome-editing and epigenome-editing technologies. As establishing causal regulatory mechanisms of diseases becomes routine, functional annotation of target genes is likely to emerge as a major bottleneck for translation into patient benefits. In this review, we discuss the history and recent advances in understanding the regulatory mechanisms of human disease, and new challenges likely to be encountered once establishing those mechanisms becomes rote. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota

PubMed Central

Cong, Y; Liu, Z

2015-01-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3+ regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders. PMID:26080708

[TNF-α, diabetes type 1 and regulatory T cells].

PubMed

Ryba, Monika; Myśliwska, Jolanta

2010-01-01

Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

Funding for the 2ND IAEA technical meeting on fusion data processing, validation and analysis

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

Greenwald, Martin

The International Atomic Energy Agency (IAEA) will organize the second Technical Meeting on Fusion Da Processing, Validation and Analysis from 30 May to 02 June, 2017, in Cambridge, MA USA. The meeting w be hosted by the MIT Plasma Science and Fusion Center (PSFC). The objective of the meeting is to provide a platform where a set of topics relevant to fusion data processing, validation and analysis are discussed with the view of extrapolation needs to next step fusion devices such as ITER. The validation and analysis of experimental data obtained from diagnostics used to characterize fusion plasmas are crucialmore » for a knowledge based understanding of the physical processes governing the dynamics of these plasmas. The meeting will aim at fostering, in particular, discussions of research and development results that set out or underline trends observed in the current major fusion confinement devices. General information on the IAEA, including its mission and organization, can be found at the IAEA websit Uncertainty quantification (UQ) Model selection, validation, and verification (V&V) Probability theory and statistical analysis Inverse problems & equilibrium reconstru ction Integrated data analysis Real time data analysis Machine learning Signal/image proc essing & pattern recognition Experimental design and synthetic diagnostics Data management« less

78 FR 44325 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... developed under the guidelines of Executive Order 12866 ``Regulatory Planning and Review.'' GSA's purpose in.... GSA also invites interested persons to recommend existing significant regulations for review to... available online at www.reginfo.gov , in a format that offers users a greatly enhanced ability to obtain...

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...

Cis-regulatory Elements and Human Evolution

PubMed Central

Siepel, Adam

2014-01-01

Modification of gene regulation has long been considered an important force in human evolution, particularly through changes to cis-regulatory elements (CREs) that function in transcriptional regulation. For decades, however, the study of cis-regulatory evolution was severely limited by the available data. New data sets describing the locations of CREs and genetic variation within and between species have now made it possible to study CRE evolution much more directly on a genome-wide scale. Here, we review recent research on the evolution of CREs in humans based on large-scale genomic data sets. We consider inferences based on primate divergence, human polymorphism, and combinations of divergence and polymorphism. We then consider “new frontiers” in this field stemming from recent research on transcriptional regulation. PMID:25218861

An inventory of ambulance service regulatory programs in California.

PubMed

Narad, R A

1998-01-01

Ambulance regulation in California is the responsibility of numerous agencies on the state and local levels. By identifying and analyzing the variety of programs used in one state, this study establishes a framework for evaluation of state and local regulatory programs elsewhere. This study surveyed all California local EMS agencies (LEMSAs: California's equivalent of regional EMS organizations) to identify the types of regulatory programs used, the foci of these programs (e.g., equipment and personnel), and their application (e.g., public and private providers). All data acquired were analyzed using population parameters rather than inferential statistics. A response rate of 100% was obtained. Among the regulatory tools used are ordinances, contracts, and franchises. Regulatory standards vary widely as do their applications. Large counties and those that operate their own LEMSA have more extensive regulatory programs than do smaller counties and those who participate in multicounty agencies. Many of the enforcement mechanisms available are weak. This study suggests several policy implications for California and other states. The wide variation in the types of regulatory programs and the standards that are used suggest that the purpose and impact of regulatory programs should be studied further. The decentralization of the ambulance regulatory program and the lack of integration of ambulance regulations into EMS system planning also raise policy questions. In addition, the role of multicounty EMS agencies, as it relates to regulation of ambulance services, should be reviewed.

Regulatory activities of transposable elements: from conflicts to benefits

PubMed Central

Chuong, Edward B.; Elde, Nels C.; Feschotte, Cédric

2017-01-01

Transposable elements (TEs) are a prolific source of tightly regulated, biochemically active non-coding elements, such as transcription factor binding sites and non-coding RNAs. A wealth of recent studies reinvigorates the idea that these elements are pervasively co-opted for the regulation of host genes. We argue that the inherent genetic properties of TEs and conflicting relationships with their hosts facilitate their recruitment for regulatory functions in diverse genomes. We review recent findings supporting the long-standing hypothesis that the waves of TE invasions endured by organisms for eons have catalyzed the evolution of gene regulatory networks. We also discuss the challenges of dissecting and interpreting the phenotypic impact of regulatory activities encoded by TEs in health and disease. PMID:27867194

Different contributions of internal reviewers and external experts to labelling decisions on therapeutic indications in new drug reviews in Japan.

PubMed

Yokota, M; Kusama, M; Matsuki, N; Ono, S

2013-12-01

External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health. © 2013 John Wiley & Sons Ltd.

Perspectives on Regulatory T Cell Therapies.

PubMed

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

Depressive Symptoms and Parenting Competence: An Analysis of 13 Regulatory Processes

ERIC Educational Resources Information Center

Dix, Theodore; Meunier, Leah N.

2009-01-01

Mechanisms that lead depressive symptoms to undermine parenting are poorly understood. This review examines cognitive, affective, and motivational processes thought to be responsible for the impact of depressive symptoms on parenting. We present a five-step, action-control model and review 152 studies relevant to 13 regulatory processes. Evidence…

77 FR 8014 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... agenda was developed under the guidelines of Executive Order 12866 ``Regulatory Planning and Review... regulations for review to determine whether they should be modified or eliminated. Proposed rules may be... Unified Agenda will be available online at www.reginfo.gov , in a format that offers users a greatly...

Changing innovation into a registered product: From concept to regulatory approval.

PubMed

Rhodes, Linda

2018-05-01

Innovation in animal health pharmaceuticals is important to address unmet and underserved medical needs, and often comes from products initially developed for human medicine. The purpose of the review is to help readers understand how breakthroughs from human biotechnology may be developed for use in veterinary medicine, while understanding the key drivers to success, the difficulties of regulatory approval, and the realistic risks and rewards of developing applications for animals. The types of human drugs which may be useful for veterinary applications are reviewed, including examples. The regulatory path is discussed, with a review of the various oversight agencies, and the categories of data required to be submitted, including safety, efficacy, manufacturing, environmental impact and human food safety. In conclusion, the cost, development time, and barriers to innovation in veterinary medical pharmaceuticals are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulatory RNA in Mycobacterium tuberculosis, back to basics.

PubMed

Schwenk, Stefan; Arnvig, Kristine B

2018-06-01

Since the turn of the millenium, RNA-based control of gene expression has added an extra dimension to the central dogma of molecular biology. Still, the roles of Mycobacterium tuberculosis regulatory RNAs and the proteins that facilitate their functions remain elusive, although there can be no doubt that RNA biology plays a central role in the baterium's adaptation to its many host environments. In this review, we have presented examples from model organisms and from M. tuberculosis to showcase the abundance and versatility of regulatory RNA, in order to emphasise the importance of these 'fine-tuners' of gene expression.

Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

PubMed Central

Liu, Zhi-Ping

2015-01-01

Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

APHIS Phytophthora ramorum regulatory strategy for nurseries

Treesearch

Jonathan M. Jones

2006-01-01

A review of the U. S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) regulatory response to Phytophthora ramorum is presented as it impacts nurseries and the nursery industry. The Agency responded in 2004 with three Federal Orders, each more restrictive than the previous one because the appropriate response called...

Environment and T regulatory cells in allergy.

PubMed

Braga, M; Schiavone, C; Di Gioacchino, G; De Angelis, I; Cavallucci, E; Lazzarin, F; Petrarca, C; Di Gioacchino, M

2012-04-15

The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries. Copyright © 2010 Elsevier B.V. All rights reserved.

Challenges posed to the European pharmaceutical regulatory system by highly personalized medicines.

PubMed

Johnston, John D; Feldschreiber, Peter

2014-03-01

The European pharmaceutical regulatory system has not yet been challenged by issues related to highly personalized medicines such as those to be found with active substances that affect RNA biochemistry. We review the current status of RNA-based pharmacology and present three possible case histories. The implications for the European pharmaceutical regulatory system are discussed. © 2013 The British Pharmacological Society.

Analysis of IAEA Environmental Samples for Plutonium and Uranium by ICP/MS in Support Of International Safeguards

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

Farmer, Orville T.; Olsen, Khris B.; Thomas, May-Lin P.

2008-05-01

A method for the separation and determination of total and isotopic uranium and plutonium by ICP-MS was developed for IAEA samples on cellulose-based media. Preparation of the IAEA samples involved a series of redox chemistries and separations using TRU® resin (Eichrom). The sample introduction system, an APEX nebulizer (Elemental Scientific, Inc), provided enhanced nebulization for a several-fold increase in sensitivity and reduction in background. Application of mass bias (ALPHA) correction factors greatly improved the precision of the data. By combining the enhancements of chemical separation, instrumentation and data processing, detection levels for uranium and plutonium approached high attogram levels.

Analytical Chemistry in the Regulatory Science of Medical Devices.

PubMed

Wang, Yi; Guan, Allan; Wickramasekara, Samanthi; Phillips, K Scott

2018-06-12

In the United States, regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all Food and Drug Administration-regulated products. Good regulatory science facilitates consumer access to innovative medical devices that are safe and effective throughout the Total Product Life Cycle (TPLC). Because the need to measure things is fundamental to the regulatory science of medical devices, analytical chemistry plays an important role, contributing to medical device technology in two ways: It can be an integral part of an innovative medical device (e.g., diagnostic devices), and it can be used to support medical device development throughout the TPLC. In this review, we focus on analytical chemistry as a tool for the regulatory science of medical devices. We highlight recent progress in companion diagnostics, medical devices on chips for preclinical testing, mass spectrometry for postmarket monitoring, and detection/characterization of bacterial biofilm to prevent infections.

Reference dosimeter system of the iaea

NASA Astrophysics Data System (ADS)

Mehta, Kishor; Girzikowsky, Reinhard

1995-09-01

Quality assurance programmes must be in operation at radiation processing facilities to satisfy national and international Standards. Since dosimetry has a vital function in these QA programmes, it is imperative that the dosimetry systems in use at these facilities are well calibrated with a traceability to a Primary Standard Dosimetry Laboratory. As a service to the Member States, the International Atomic Energy Agency operates the International Dose Assurance Service (IDAS) to assist in this process. The transfer standard dosimetry system that is used for this service is based on ESR spectrometry. The paper describes the activities undertaken at the IAEA Dosimetry Laboratory to establish the QA programme for its reference dosimetry system. There are four key elements of such a programme: quality assurance manual; calibration that is traceable to a Primary Standard Dosimetry Laboratory; a clear and detailed statement of uncertainty in the dose measurement; and, periodic quality audit.

Positive lists of cosmetic ingredients: Analytical methodology for regulatory and safety controls - A review.

PubMed

Lores, Marta; Llompart, Maria; Alvarez-Rivera, Gerardo; Guerra, Eugenia; Vila, Marlene; Celeiro, Maria; Lamas, J Pablo; Garcia-Jares, Carmen

2016-04-07

Cosmetic products placed on the market and their ingredients, must be safe under reasonable conditions of use, in accordance to the current legislation. Therefore, regulated and allowed chemical substances must meet the regulatory criteria to be used as ingredients in cosmetics and personal care products, and adequate analytical methodology is needed to evaluate the degree of compliance. This article reviews the most recent methods (2005-2015) used for the extraction and the analytical determination of the ingredients included in the positive lists of the European Regulation of Cosmetic Products (EC 1223/2009): comprising colorants, preservatives and UV filters. It summarizes the analytical properties of the most relevant analytical methods along with the possibilities of fulfilment of the current regulatory issues. The cosmetic legislation is frequently being updated; consequently, the analytical methodology must be constantly revised and improved to meet safety requirements. The article highlights the most important advances in analytical methodology for cosmetics control, both in relation to the sample pretreatment and extraction and the different instrumental approaches developed to solve this challenge. Cosmetics are complex samples, and most of them require a sample pretreatment before analysis. In the last times, the research conducted covering this aspect, tended to the use of green extraction and microextraction techniques. Analytical methods were generally based on liquid chromatography with UV detection, and gas and liquid chromatographic techniques hyphenated with single or tandem mass spectrometry; but some interesting proposals based on electrophoresis have also been reported, together with some electroanalytical approaches. Regarding the number of ingredients considered for analytical control, single analyte methods have been proposed, although the most useful ones in the real life cosmetic analysis are the multianalyte approaches. Copyright © 2016

Impact of regulatory science on global public health.

PubMed

Patel, Meghal; Miller, Margaret Ann

2012-07-01

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies. Copyright © 2012. Published by Elsevier B.V.

Comparing Distributions of Environmental Outcomes for Regulatory Environmental Justice Analysis

PubMed Central

Maguire, Kelly; Sheriff, Glenn

2011-01-01

Economists have long been interested in measuring distributional impacts of policy interventions. As environmental justice (EJ) emerged as an ethical issue in the 1970s, the academic literature has provided statistical analyses of the incidence and causes of various environmental outcomes as they relate to race, income, and other demographic variables. In the context of regulatory impacts, however, there is a lack of consensus regarding what information is relevant for EJ analysis, and how best to present it. This paper helps frame the discussion by suggesting a set of questions fundamental to regulatory EJ analysis, reviewing past approaches to quantifying distributional equity, and discussing the potential for adapting existing tools to the regulatory context. PMID:21655146

Meeting the challenges of global nuclear medicine technologist training in the 21st century: the IAEA Distance Assisted Training (DAT) program.

PubMed

Patterson, Heather E; Nunez, Margarita; Philotheou, Geraldine M; Hutton, Brian F

2013-05-01

Many countries have made significant investments in nuclear medicine (NM) technology with the acquisition of modern equipment and establishment of facilities, however, often appropriate training is not considered as part of these investments. Training for NM professionals is continually evolving, with a need to meet changing requirements in the workforce. Even places where established higher education courses are available, these do not necessarily cater to the practical component of training and the ever-changing technology that is central to medical imaging. The continuing advances in NM technology and growth of applications in quantitative clinical assessment place increases the pressure on technologists to learn and practice new techniques. Not only is training to understand new concepts limited but often there is inadequate training in the basics of NM and this can be a major constraint to the effective use of the evolving technology. Developing appropriate training programs for the broader international NM community is one of the goals of the International Atomic Energy Agency (IAEA). A particularly successful and relevant development has been the program on 'distance assisted training (DAT) for NM professionals'. The development of DAT was initiated in the 1990s through Australian Government funding, administered under auspices of the IAEA through its Regional Cooperative Agreement, involving most countries in Asia that are Member States of the IAEA. The project has resulted in the development of a set of training modules which are designed for use under direct supervision in the workplace, delivered through means of distance-learning. The program has undergone several revisions and peer reviews with the current version providing a comprehensive training package that is now available online. DAT has been utilized widely in Asia or the Pacific region, Latin America, and parts of Africa and Europe. Currently there are approximately 1000 registered participants

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

Regulatory assessment of chemical mixtures: Requirements, current approaches and future perspectives.

PubMed

Kienzler, Aude; Bopp, Stephanie K; van der Linden, Sander; Berggren, Elisabet; Worth, Andrew

2016-10-01

This paper reviews regulatory requirements and recent case studies to illustrate how the risk assessment (RA) of chemical mixtures is conducted, considering both the effects on human health and on the environment. A broad range of chemicals, regulations and RA methodologies are covered, in order to identify mixtures of concern, gaps in the regulatory framework, data needs, and further work to be carried out. Also the current and potential future use of novel tools (Adverse Outcome Pathways, in silico tools, toxicokinetic modelling, etc.) in the RA of combined effects were reviewed. The assumptions made in the RA, predictive model specifications and the choice of toxic reference values can greatly influence the assessment outcome, and should therefore be specifically justified. Novel tools could support mixture RA mainly by providing a better understanding of the underlying mechanisms of combined effects. Nevertheless, their use is currently limited because of a lack of guidance, data, and expertise. More guidance is needed to facilitate their application. As far as the authors are aware, no prospective RA concerning chemicals related to various regulatory sectors has been performed to date, even though numerous chemicals are registered under several regulatory frameworks. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

T regulatory cells: an overview and intervention techniques to modulate allergy outcome

PubMed Central

Nandakumar, Subhadra; Miller, Christopher WT; Kumaraguru, Uday

2009-01-01

Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals. PMID:19284628

Secretary of Energy Steven Chu speaks to the 2009 IAEA General Conference delegation

ScienceCinema

Secretary Chu

2017-12-09

On Sept. 14, 2009, U.S. Secretary of Energy Steven Chu addressed the 2009 IAEA General Conference delegation. Chu is the first Cabinet official to discuss President Obama's nuclear security and nonproliferation agenda outside the United States since the President delivered his landmark speech in Prague in April 2009.

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

Cannabis regulatory science: risk-benefit considerations for mental disorders.

PubMed

Borodovsky, Jacob T; Budney, Alan J

2018-05-29

The evolving legal cannabis landscape in the US continues to present novel regulatory challenges that necessitate the development of a Cannabis Regulatory Science. Two specific issues of concern within Cannabis Regulatory Science are (1) the impact that cannabis use has on the incidence, prevalence, and severity of mental disorders, and (2) how cannabis laws and regulations modify this impact. This paper first provides several conceptual points that are useful for evaluating the relationship between cannabis use and mental disorders. Second, it selectively reviews and comments on data relevant to the relationship between cannabis use and depression, several forms of anxiety, post-traumatic stress disorder, schizophrenia, and bipolar disorder. Next, regulatory and public health parallels between the nascent cannabis industry and the pharmaceutical, tobacco, and alcohol industries are discussed. The focus is on specific types of industry practices that may harm those with or at risk for mental disorders. Recommendations are then offered for legal cannabis regulations that could mitigate this harm. Last, future research goals are discussed for building the field of Cannabis Regulatory Science and addressing the potential negative impact of cannabis on those with mental disorders.

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

Comparative analysis of gene regulatory networks: from network reconstruction to evolution.

PubMed

Thompson, Dawn; Regev, Aviv; Roy, Sushmita

2015-01-01

Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation.

Identification and role of regulatory non-coding RNAs in Listeria monocytogenes.

PubMed

Izar, Benjamin; Mraheil, Mobarak Abu; Hain, Torsten

2011-01-01

Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a plethora of biological processes, such as the adaption to environmental changes, growth and virulence. Recently developed high-throughput techniques, such as genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- and trans-acting regulatory RNAs, including sRNAs, asRNAs, untranslated regions (UTR) and riboswitches. As a result, we obtained a more comprehensive view on the complexity and plasticity of the prokaryotic genome biology. Listeria monocytogenes was utilized as a model system for intracellular pathogenic bacteria in several studies, which revealed the presence of about 180 regulatory RNAs in the listerial genome. A regulatory role of non-coding RNAs in survival, virulence and adaptation mechanisms of L. monocytogenes was confirmed in subsequent experiments, thus, providing insight into a multifaceted modulatory function of RNA/mRNA interference. In this review, we discuss the identification of regulatory RNAs by high-throughput techniques and in their functional role in L. monocytogenes.

78 FR 1624 - Fall 2012 Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

...The Environmental Protection Agency (EPA) publishes the semiannual regulatory agenda online (the e-Agenda) at http:// www.reginfo.gov and at www.regulations.gov to update the public about: Regulations and major policies currently under development; reviews of existing regulations and major policies; and rules and major policy makings completed or canceled since the publication of the last agenda.

77 FR 73060 - Standard Review Plan for Review of Fuel Cycle Facility License Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0220] Standard Review Plan for Review of Fuel Cycle... 1, ``Standard Review Plan (SRP) for the Review of a License Application for a Fuel Cycle Facility... for a fuel cycle facility (NUREG-1520) provides NRC staff guidance for reviewing and evaluating the...

The legislative and regulatory framework governing herbal medicine use and practice in Kenya: a review.

PubMed

Okumu, Mitchel Otieno; Ochola, Francis Okumu; Onyango, Allan Odhiambo; Mbaria, James Mucunu; Gakuya, Daniel Waweru; Kanja, Laetitia Wakonyu; Kiama, Stephen Gitahi; Onyango, Mary Atieno

2017-01-01

Complementary and alternative medicine is an integral component of primary healthcare in Kenya. This is because the infrastructural health setup in the country is inadequate in catering for all the medical needs of the population. This particularly holds true in the rural areas where many rural folk rely on products of herbal origin to offset their healthcare needs. More often than not these products are an elaborate cacophony of several different substances of biological origin and thus need personnel adept in their preparation. Sadly, due to loopholes in legislation and regulation, quacks have a field day in the practice. Moreover, the process of planting, harvesting, preparation and storage of herbs and related products dictates that a significant number of people will ultimately be involved in the whole process. This is likely to set the stage for manipulation and compromise of the safety, quality and efficacy of these products. This state of affairs appears unabated especially in the context of the current legal and regulatory framework governing herbal medicine use and practice in Kenya. Not only are these laws inadequate, they are shrouded in ambiguity, open to interpretation and the authorities mandated to implement them often end up performing duplicate roles. The aim of this review is to critique the legal and regulatory provisions governing herbal medicine use and practice in Kenya. In conclusion, laws and regulations meant to control herbal medicine use and practice in Kenya are wanting. Clear and definitive legislation on herbal medicine use and practice coupled with effective implementation by mandated institutions will go a long way in inspiring confidence to all stakeholders of herbal medicine.

The legislative and regulatory framework governing herbal medicine use and practice in Kenya: a review

PubMed Central

Okumu, Mitchel Otieno; Ochola, Francis Okumu; Onyango, Allan Odhiambo; Mbaria, James Mucunu; Gakuya, Daniel Waweru; Kanja, Laetitia Wakonyu; Kiama, Stephen Gitahi; Onyango, Mary Atieno

2017-01-01

Complementary and alternative medicine is an integral component of primary healthcare in Kenya. This is because the infrastructural health setup in the country is inadequate in catering for all the medical needs of the population. This particularly holds true in the rural areas where many rural folk rely on products of herbal origin to offset their healthcare needs. More often than not these products are an elaborate cacophony of several different substances of biological origin and thus need personnel adept in their preparation. Sadly, due to loopholes in legislation and regulation, quacks have a field day in the practice. Moreover, the process of planting, harvesting, preparation and storage of herbs and related products dictates that a significant number of people will ultimately be involved in the whole process. This is likely to set the stage for manipulation and compromise of the safety, quality and efficacy of these products. This state of affairs appears unabated especially in the context of the current legal and regulatory framework governing herbal medicine use and practice in Kenya. Not only are these laws inadequate, they are shrouded in ambiguity, open to interpretation and the authorities mandated to implement them often end up performing duplicate roles. The aim of this review is to critique the legal and regulatory provisions governing herbal medicine use and practice in Kenya. In conclusion, laws and regulations meant to control herbal medicine use and practice in Kenya are wanting. Clear and definitive legislation on herbal medicine use and practice coupled with effective implementation by mandated institutions will go a long way in inspiring confidence to all stakeholders of herbal medicine. PMID:29629018

Regulatory and clinical considerations for biosimilar oncology drugs

PubMed Central

Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O

2015-01-01

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve healthcare access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns. PMID:25456378

Regulatory guidance on soil cover systems

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

Kane, J.D.

1991-12-31

The US Nuclear Regulatory Commission (NRC) in September 1991, completed revisions to 14 sections of the Standard Review Plan (SRP) for the Review of a License Application for a Low-Level Radioactive Waste Disposal Facility. The major purposes of the SRP are to ensure the quality and uniformity of the NRC staff`s safety reviews, and to present a well-defined base from which to evaluate the acceptability of information and data provided in the Safety Analysis Report (SAR) portion of the license application. SRP 3.2, entitled, Design Considerations for Normal and Abnormal/Accident Conditions, was one of the sections that was revised bymore » the NRC staff. This revision was completed to provide additional regulatory guidance on the important considerations that need to be addressed for the proper design and construction of soil cover systems that are to be placed over the LLW. The cover system over the waste is acknowledged to be one of the most important engineered barriers for the long-term stable performance of the disposal facility. The guidance in revised SRP 3.2 summarizes the previous efforts and recommendations of the US Army Corps of Engineers (COE), and a peer review panel on the placement of soil cover systems. NRC published these efforts in NUREG/CR-5432. The discussions in this paper highlight selected recommendations on soil cover issues that the NRC staff considers important for ensuring the safe, long-term performance of the soil cover systems. The development phases to be discussed include: (1) cover design; (2) cover material selection; (3) laboratory and field testing; (4) field placement control and acceptance; and (5) penetrations through the constructed covers.« less

Quality of radiotherapy services in post-Soviet countries: An IAEA survey.

PubMed

Rosenblatt, Eduardo; Fidarova, Elena; Ghosh, Sunita; Zubizarreta, Eduardo; Unterkirhere, Olga; Semikoz, Natalia; Sinaika, Valery; Kim, Viktor; Karamyan, Nerses; Isayev, Isa; Akbarov, Kamal; Lomidze, Darejan; Bondareva, Oksana; Tuzlucov, Piotr; Zardodkhonova, Manzura; Tkachev, Sergey; Kislyakova, Marina; Alimov, Jamshid; Pidlubna, Tetiana; Barton, Michael; Mackillop, William

2018-04-25

The quality of radiotherapy services in post-Soviet countries has not yet been studied following a formal methodology. The IAEA conducted a survey using two sets of validated radiation oncology quality indicators (ROIs). Eleven post-Soviet countries were assessed. A coordinator was designated for each country and acted as the liaison between the country and the IAEA. The methodology was a one-time cross-sectional survey using a 58-question tool in Russian. The questionnaire was based on two validated sets of ROIs: for radiotherapy centres, the indicators proposed by Cionini et al., and for data at the country level, the Australasian ROIs. The overall response ratio was 66.3%, but for the Russian Federation, it was 24%. Data were updated on radiotherapy infrastructure and equipment. 256 radiotherapy centres are operating 275 linear accelerators and 337 Cobalt-60 units. 61% of teletherapy machines are older than ten years. Analysis of ROIs revealed significant differences between these countries and radiotherapy practices in the West. Naming, task profile and education programmes of radiotherapy professionals are different than in the West. Most countries need modernization of their radiotherapy infrastructure coupled with adequate staffing numbers and updated education programmes focusing on evidence-based medicine, quality, and safety. Copyright © 2018 Elsevier B.V. All rights reserved.

Deep conservation of cis-regulatory elements in metazoans

PubMed Central

Maeso, Ignacio; Irimia, Manuel; Tena, Juan J.; Casares, Fernando; Gómez-Skarmeta, José Luis

2013-01-01

Despite the vast morphological variation observed across phyla, animals share multiple basic developmental processes orchestrated by a common ancestral gene toolkit. These genes interact with each other building complex gene regulatory networks (GRNs), which are encoded in the genome by cis-regulatory elements (CREs) that serve as computational units of the network. Although GRN subcircuits involved in ancient developmental processes are expected to be at least partially conserved, identification of CREs that are conserved across phyla has remained elusive. Here, we review recent studies that revealed such deeply conserved CREs do exist, discuss the difficulties associated with their identification and describe new approaches that will facilitate this search. PMID:24218633

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

PubMed

de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo

2017-01-01

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. © 2016 Japanese Dermatological Association.

75 FR 57460 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... Information Management Services, Office of Management invites comments on the submission for OMB review as... Office of Information and Regulatory Affairs, Attention: Education Desk Officer, Office of Management and..., Regulatory Information Management Services, Office of Management. Federal Student Aid Type of Review: New...

10 CFR 75.46 - Expenses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Expenses. 75.46 Section 75.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Advanced Notification and Expenses § 75.46 Expenses. (a) Under the Safeguards Agreement, the IAEA undertakes to...

10 CFR 75.46 - Expenses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Expenses. 75.46 Section 75.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Advanced Notification and Expenses § 75.46 Expenses. (a) Under the Safeguards Agreement, the IAEA undertakes to...

76 FR 66332 - Appointments to Performance Review Boards for Senior Executive Service

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0249] Appointments to Performance Review Boards for Senior Executive Service AGENCY: U.S. Nuclear Regulatory Commission. ACTION: Appointment to Performance Review... the following appointments to the NRC Performance Review Boards. The following individuals are...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

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...

IAEA coordinated research project on thermal-hydraulics of Supercritical Water-Cooled Reactors (SCWRs)

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

Yamada, K.; Aksan, S. N.

The Supercritical Water-Cooled Reactor (SCWR) is an innovative water-cooled reactor concept, which uses supercritical pressure water as reactor coolant. It has been attracting interest of many researchers in various countries mainly due to its benefits of high thermal efficiency and simple primary systems, resulting in low capital cost. The IAEA started in 2008 a Coordinated Research Project (CRP) on Thermal-Hydraulics of SCWRs as a forum to foster the exchange of technical information and international collaboration in research and development. This paper summarizes the activities and current status of the CRP, as well as major progress achieved to date. At present,more » 15 institutions closely collaborate in several tasks. Some organizations have been conducting thermal-hydraulics experiments and analysing the data, and others have been participating in code-to-test and/or code-to-code benchmark exercises. The expected outputs of the CRP are also discussed. Finally, the paper introduces several IAEA activities relating to or arising from the CRP. (authors)« less

Regulatory T cells: present facts and future hopes.

PubMed

Becker, Christian; Stoll, Sabine; Bopp, Tobias; Schmitt, Edgar; Jonuleit, Helmut

2006-09-01

Naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells and several subsets of induced suppressor T cells are key players of the immune tolerance network and control the induction and effector phase of our immunological defense system. These T cell populations actively control the properties of other immune cells by suppressing their functional activity to prevent autoimmunity and transplant rejection but also influence the immune response to allergens as well as against tumor cells and pathogens. Even though we are far from completely understanding the molecular and cellular mechanisms that manage the different regulatory T cell populations, increasing evidence exists about their functional importance. The knowledge on their induction and activation opens the possibility for their selective manipulation in vivo as an attractive approach for an immunotherapy of unwanted immune responses. This review summarizes this knowledge and discusses the potential of regulatory T cells for novel immunointervention strategies in the future.

Genetically engineered crops for biofuel production: regulatory perspectives.

PubMed

Lee, David; Chen, Alice; Nair, Ramesh

2008-01-01

There are numerous challenges in realizing the potential of biofuels that many policy makers have envisioned. The technical challenges in making the production of biofuels economical and on a scale to replace a significant fraction of transportation fuel have been well described, along with the potential environmental concerns. The use of biotechnology can potentially address many of these technical challenges and environmental concerns, but brings significant regulatory hurdles that have not been discussed extensively in the scientific community. This review will give an overview of the approaches being developed to produce transgenic biofuel feedstocks, particularly cellulosic ethanol, and the regulatory process in the United States that oversees the development and commercialization of new transgenic plants. We hope to illustrate that the level of regulation for transgenic organisms is not proportional to their potential risk to human health or the environment, and that revisions to the regulatory system in the U.S. currently under consideration are necessary to streamline the process.

Examining characteristics, knowledge and regulatory practices of specialized drug shops in Sub-Saharan Africa: a systematic review of the literature.

PubMed

Wafula, Francis N; Miriti, Eric M; Goodman, Catherine A

2012-07-27

Specialized drug shops such as pharmacies and drug shops are increasingly becoming important sources of treatment. However, knowledge on their regulatory performance is scarce. We set out to systematically review literature on the characteristics, knowledge and practices of specialized drug shops in Sub-Saharan Africa. We searched PubMed, EMBASE, WEB of Science, CAB Abstracts, PsycINFO and websites for organizations that support medicine policies and usage. We also conducted open searches using Google Scholar, and searched manually through references of retrieved articles. Our search included studies of all designs that described characteristics, knowledge and practices of specialized drug shops. Information was abstracted on authors, publication year, country and location, study design, sample size, outcomes investigated, and primary findings using a uniform checklist. Finally, we conducted a structured narrative synthesis of the main findings. We obtained 61 studies, mostly from Eastern Africa, majority of which were conducted between 2006 and 2011. Outcome measures were heterogeneous and included knowledge, characteristics, and dispensing and regulatory practices. Shop location and client demand were found to strongly influence dispensing practices. Whereas shops located in urban and affluent areas were more likely to provide correct treatments, those in rural areas provided credit facilities more readily. However, the latter also charged higher prices for medicines. A vast majority of shops simply sold whatever medicines clients requested, with little history taking and counseling. Most shops also stocked popular medicines at the expense of policy recommended treatments. Treatment policies were poorly communicated overall, which partly explained why staff had poor knowledge on key aspects of treatment such as medicine dosage and side effects. Overall, very little is known on the link between regulatory enforcement and practices of specialized drug shops

Rapid development of tissue bank achieved by International Atomic Energy Agency (IAEA) Tissue Banking Programme in China.

PubMed

Zhang, Yu-Min; Wang, Jian-Ru; Zhang, Nai-Li; Liu, Xiao-Ming; Zhou, Mo; Ma, Shao-Ying; Yang, Ting; Li, Bao-Xing

2014-09-01

Before 1986, the development of tissue banking in China has been slow and relatively uncoordinated. Under the support of International Atomic Energy Agency (IAEA), Tissue Banking in China experienced rapid development. In this period, China Institute for Radiation Protection tissue bank mastered systematic and modern tissue banking technique by IAEA training course and gradually developed the first regional tissue bank (Shanxi Provincial Tissue Bank, SPTB) to provide tissue allograft. Benefit from training course, SPTB promoted the development of tissue transplantation by ways of training, brochure, advertisement and meeting. Tissue allograft transplantation acquired recognition from clinic and supervision and administration from government. Quality system gradually is developing and perfecting. Tissue allograft transplantation and tissue bank are developing rapidly and healthy.

A test of the IAEA code of practice for absorbed dose determination in photon and electron beams

NASA Astrophysics Data System (ADS)

Leitner, Arnold; Tiefenboeck, Wilhelm; Witzani, Josef; Strachotinsky, Christian

1990-12-01

The IAEA (International Atomic Energy Agency) code of practice TRS 277 gives recommendations for absorbed dose determination in high energy photon and electron beams based on the use of ionization chambers calibrated in terms of exposure of air kerma. The scope of the work was to test the code for cobalt 60 gamma radiation and for several radiation qualities at four different types of electron accelerators and to compare the ionization chamber dosimetry with ferrous sulphate dosimetry. The results show agreement between the two methods within about one per cent for all the investigated qualities. In addition the response of the TLD capsules of the IAEA/WHO TL dosimetry service was determined.

The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

PubMed

Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

2011-04-01

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust.

PubMed

Cazap, Eduardo; Jacobs, Ira; McBride, Ali; Popovian, Robert; Sikora, Karol

2018-05-16

Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars

Digital management and regulatory submission of medical images from clinical trials: role and benefits of the core laboratory

NASA Astrophysics Data System (ADS)

Robbins, William L.; Conklin, James J.

1995-10-01

Medical images (angiography, CT, MRI, nuclear medicine, ultrasound, x ray) play an increasingly important role in the clinical development and regulatory review process for pharmaceuticals and medical devices. Since medical images are increasingly acquired and archived digitally, or are readily digitized from film, they can be visualized, processed and analyzed in a variety of ways using digital image processing and display technology. Moreover, with image-based data management and data visualization tools, medical images can be electronically organized and submitted to the U.S. Food and Drug Administration (FDA) for review. The collection, processing, analysis, archival, and submission of medical images in a digital format versus an analog (film-based) format presents both challenges and opportunities for the clinical and regulatory information management specialist. The medical imaging 'core laboratory' is an important resource for clinical trials and regulatory submissions involving medical imaging data. Use of digital imaging technology within a core laboratory can increase efficiency and decrease overall costs in the image data management and regulatory review process.

Meeting Regulatory Needs.

PubMed

Weber, Michael Fred

2017-02-01

The world is experiencing change at an unprecedented pace, as reflected in social, cultural, economic, political, and technological advances around the globe. Regulatory agencies, like the U.S. Nuclear Regulatory Commission (NRC), must also transform in response to and in preparation for these changes. In 2014, the NRC staff commenced Project Aim 2020 to transform the agency by enhancing efficiency, agility, and responsiveness, while accomplishing NRC's safety and security mission. Following Commission review and approval in 2015, the NRC began implementing the approved strategies, including strategic workforce planning to provide confidence that NRC will have employees with the right skills and talents at the right time to accomplish the agency's mission. Based on the work conducted so far, ensuring an adequate pipeline of radiation protection professionals is a significant need that NRC shares with states and other government agencies, private industry, academia, as well as international counterparts. NRC is working to ensure that sufficient radiation protection professionals will be available to fulfill its safety and security mission and leverage the work of the National Council on Radiation Protection and Measurements, the Conference of Radiation Control Program Directors, the Health Physics Society, the Organization of Agreement States, the International Atomic Energy Agency, the Nuclear Energy Agency, and others.

Regulatory T cells: mechanisms of differentiation and function.

PubMed

Josefowicz, Steven Z; Lu, Li-Fan; Rudensky, Alexander Y

2012-01-01

The immune system has evolved to mount an effective defense against pathogens and to minimize deleterious immune-mediated inflammation caused by commensal microorganisms, immune responses against self and environmental antigens, and metabolic inflammatory disorders. Regulatory T (Treg) cell-mediated suppression serves as a vital mechanism of negative regulation of immune-mediated inflammation and features prominently in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation. The discovery that Foxp3 is the transcription factor that specifies the Treg cell lineage facilitated recent progress in understanding the biology of regulatory T cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of these cells.

Regulatory B-cell induction by helminths: implications for allergic disease.

PubMed

Hussaarts, Leonie; van der Vlugt, Luciën E P M; Yazdanbakhsh, Maria; Smits, Hermelijn H

2011-10-01

Chronic helminth infections are often associated with a reduced prevalence of inflammatory disorders, including allergic diseases. Helminths influence the host immune system by downregulating T-cell responses; the cytokine IL-10 appears to play a central role in this process. Over the last decade, evidence has emerged toward a new regulatory cell type: IL-10-producing B cells, capable of regulating immunity and therefore termed regulatory B cells. Initially, regulatory B cells have been described in autoimmunity models where they dampen inflammation, but recently they were also found in several helminth infection models. Importantly, regulatory B cells have recently been identified in humans, and it has been suggested that patients suffering from autoimmunity have an impaired regulatory B-cell function. As such, it is of therapeutic interest to study the conditions in which IL-10-producing B cells can be induced. Chronic helminth infections appear to hold promise in this context as emerging evidence suggests that helminth-induced regulatory B cells strongly suppress allergic inflammation. In this review, we will discuss the conditions under which regulatory B cells are present, leading to a state of tolerance, as well as the conditions where their absence or functional impairment leads to exacerbated disease. We will summarize their phenotypic characteristics and their mechanisms of action and elaborate on possible mechanisms whereby regulatory B cells can be induced or expanded, as this may open novel avenues for the treatment of inflammatory diseases, such as allergic asthma. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

10 CFR 75.33 - Accounting reports.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Accounting reports. 75.33 Section 75.33 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Reports § 75.33 Accounting reports. (a)(1) The accounting reports for each IAEA material balance area must...

10 CFR 75.33 - Accounting reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Accounting reports. 75.33 Section 75.33 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT Reports § 75.33 Accounting reports. (a)(1) The accounting reports for each IAEA material balance area must...

Regulatory Myeloid Cells in Transplantation

PubMed Central

Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

2013-01-01

Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

Measurement of ²²⁶Ra in soil from oil field: advantages of γ-ray spectrometry and application to the IAEA-448 CRM.

PubMed

Ceccatelli, A; Katona, R; Kis-Benedek, G; Pitois, A

2014-05-01

The analytical performance of gamma-ray spectrometry for the measurement of (226)Ra in TENORM (Technically Enhanced Naturally Occurring Radioactive Material) soil was investigated by the IAEA. Fast results were obtained for characterization and certification of a new TENORM Certified Reference Material (CRM), identified as IAEA-448 (soil from oil field). The combined standard uncertainty of the gamma-ray spectrometry results is of the order of 2-3% for massic activity measurement values ranging from 16500 Bq kg(-1) to 21500 Bq kg(-1). Methodologies used for the production and certification of the IAEA-448 CRM are presented. Analytical results were confirmed by alpha spectrometry. The "t" test showed agreement between alpha and gamma results at 95% confidence level. © 2013 Published by Elsevier Ltd.

Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk

PubMed Central

Shaffer, Fred

2015-01-01

Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems. PMID:25694852

Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

PubMed

McCraty, Rollin; Shaffer, Fred

2015-01-01

Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

From molecule to market access: drug regulatory science as an upcoming discipline.

PubMed

Gispen-de Wied, Christine C; Leufkens, Hubertus G M

2013-11-05

Regulatory science as a discipline has evolved over the past years with the object to boost and promote scientific rationale behind benefit/risk and decision making by regulatory authorities. The European Medicines Agency, EMA, the Food and Drug Administration, FDA, and the Japanese Pharmaceutical and Medical Devices Agency, PMDA, highlighted in their distinct ways the importance of regulatory science as a basis of good quality assessment in their strategic plans. The Medicines Evaluation Board, MEB, states: 'regulatory science is the science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making'. Through analysis of regulatory frameworks itself and their effectiveness, however, regulatory science can also advance knowledge of these systems in general. The comprehensive guidance that is issued to complete an application dossier for regulatory product approval has seldomly been scrutinized for its efficiency. Since it is the task of regulatory authorities to protect and promote public health, it is understood that they take a cautious approach in regulating drugs prior to market access. In general, the authorities are among the first to be blamed if dangerous or useless drugs were allowed to the market. Yet, building a regulatory framework that is not challenged continuously in terms of deliverables for public health and cost-effectiveness, might be counterproductive in the end. Regulatory science and research can help understand how and why regulatory decisions are made, and where renewed discussions may be warranted. The MEB supports regulatory science as an R&D activity to fuel primary regulatory processes on product evaluation and vigilance, but also invests in a 'looking into the mirror' approach. Along the line of the drug life-cycle, publicly available data are reviewed and their regulatory impact highlighted. If made explicit

Papers arising from IAEA Coordinated Research Project "Utilization of ion accelerators for studying and modelling of radiation induced defects in semiconductors and insulators" (F11016)

NASA Astrophysics Data System (ADS)

Vittone, Ettore; Breese, Mark; Simon, Aliz

2016-04-01

Within the International Atomic Energy Agency (IAEA) Department of Nuclear Sciences and Applications, activities are carried out to assist and advise IAEA Member States in assessing their needs for capacity building, research and development in nuclear sciences. Support is also provided to Member States' activities geared towards deriving benefits in fields such as (i) advanced materials for nuclear applications, (ii) application of accelerators and associated instrumentation, and (iii) nuclear, atomic and molecular data. One of the means that the IAEA uses to deliver its programme is Coordinated Research Projects (CRPs) which are very effective in stimulating international research and scientific interaction among the Member States.

Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.

PubMed

Ndebele, Paul; Blanchard-Horan, Christina; Shahkolahi, Akbar; Sanne, Ian

2014-01-01

International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

77 FR 6094 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

....-International Atomic Energy Agency Additional Protocol. Under the U.S.-International Atomic Energy Agency (IAEA...-related activities to the IAEA and potentially provide access to IAEA inspectors for verification purposes. The U.S.-IAEA Additional Protocol permits the United States unilaterally to declare exclusions from...

TU-AB-BRC-07: Efficiency of An IAEA Phase-Space Source for a Low Energy X-Ray Tube Using Egs++

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

Watson, PGF; Renaud, MA; Seuntjens, J

Purpose: To extend the capability of the EGSnrc C++ class library (egs++) to write and read IAEA phase-space files as a particle source, and to assess the relative efficiency gain in dose calculation using an IAEA phase-space source for modelling a miniature low energy x-ray source. Methods: We created a new ausgab object to score particles exiting a user-defined geometry and write them to an IAEA phase-space file. A new particle source was created to read from IAEA phase-space data. With these tools, a phase-space file was generated for particles exiting a miniature 50 kVp x-ray tube (The INTRABEAM System,more » Carl Zeiss). The phase-space source was validated by comparing calculated PDDs with a full electron source simulation of the INTRABEAM. The dose calculation efficiency gain of the phase-space source was determined relative to the full simulation. The efficiency gain as a function of i) depth in water, and ii) job parallelization was investigated. Results: The phase-space and electron source PDDs were found to agree to 0.5% RMS, comparable to statistical uncertainties. The use of a phase-space source for the INTRABEAM led to a relative efficiency gain of greater than 20 over the full electron source simulation, with an increase of up to a factor of 196. The efficiency gain was found to decrease with depth in water, due to the influence of scattering. Job parallelization (across 2 to 256 cores) was not found to have any detrimental effect on efficiency gain. Conclusion: A set of tools has been developed for writing and reading IAEA phase-space files, which can be used with any egs++ user code. For simulation of a low energy x-ray tube, the use of a phase-space source was found to increase the relative dose calculation efficiency by factor of up to 196. The authors acknowledge partial support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant No. 432290).« less

76 FR 15859 - Reducing Regulatory Burden; Retrospective Review under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

... Management, at (202) 501- 1777. SUPPLEMENTARY INFORMATION: A. Background Executive Order 13563 directs each..., ineffective, insufficient, or excessively burdensome.'' The EO calls on every agency to develop ``a... modified, streamlined, expanded or repealed to make the agency's regulatory program more effective and or...

[Evaluation of regulatory policies: the prevention of traffic accidents in Spain].

PubMed

Villalbí, Joan R; Pérez, Catherine

2006-03-01

Traffic accident injuries may be reduced with public policies. We review regulatory policies extending beyond the health sector by studying the case of traffic accident injuries. They have been the object of other analyses in Spain by both health professionals and professionals from other sectors, but we have not found a previous thorough review including regulatory aspects. We analyze the evolution of fatal victims of traffic accidents as collected by the Dirección General de Tráfico, stratifying for pedestrians, two-wheel vehicle occupants and occupants of other vehicles, and breaking down accidents between those occurring in roads and in urban settings. Despite the increase in exposure factors between 1970 and 2003, we observe a strong impact of regulatory policies in accident mortality. A favorable impact is seen for regulations and enforcement actions on motorcycle helmets, speed limits and the control of alcohol use, and a lower impact for safety belts, perhaps because its actual effective implementation was not equally sharp. The adoption of comprehensive plans or complex legislation packages seems to have had a positive impact, perhaps attributable to its triggering of more effective enforcement of already existing regulations. Although the existence of legal norms is not enough in itself, as its impact is low without active enforcement, compliance improves over time. In any case, the existence of specific initiatives to influence this field is important to obtain the best results of regulatory policies in public health.

77 FR 75676 - Standard Review Plan for Review of Fuel Cycle Facility License Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0220] Standard Review Plan for Review of Fuel Cycle... Review of a License Application for a Fuel Cycle Facility.'' The NRC is extending the public comment... of Fuel Cycle Safety and Safeguards, Office of Nuclear Material Safety and Safeguards. [FR Doc. 2012...

Seabed gamma-ray spectrometry: applications at IAEA-MEL.

PubMed

Osvath, I; Povinec, P P

2001-01-01

The technique of underwater gamma-ray spectrometry has been developed to complement or replace the traditional sampling-sample analysis approach for applications with space-time constraints, e.g. large areas of investigation, emergency response or long-term monitoring. IAEA-MEL has used both high-efficiency NaI(Tl) and high-resolution HPGe spectrometry to investigate contamination with anthropogenic radionuclides in a variety of marine environments. Surveys at the South Pacific nuclear test sites of Mururoa and Fangataufa have been used to guide sampling in areas of high contamination around ground zero points. In the Irish Sea offshore from the Sellafield nuclear reprocessing plant, a gamma-ray survey of seabed sediment was carried out to obtain estimates of the distribution and subsequently, for the inventory of 137Cs in the investigated area.

78 FR 19540 - Memorandum of Understanding Between the U.S. Nuclear Regulatory Commission and the Bureau of Land...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... Regulatory Commission and the Bureau of Land Management AGENCY: Nuclear Regulatory Commission. ACTION: Notice... Review Branch, Division of Waste Management and Environmental Protection, Office of Federal and State... the Bureau of Land Management, United States Department of the Interior (BLM) entered into a...

Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne L.

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However,more » it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated

Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne Leland

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However,more » it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated

Actual operation and regulatory activities on steam generator replacement in Japan

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

Saeki, Hitoshi

1997-02-01

This paper summarizes the operating reactors in Japan, and the status of the steam generators in these plants. It reviews plans for replacement of existing steam generators, and then goes into more detail on the planning and regulatory steps which must be addressed in the process of accomplishing this maintenance. The paper also reviews the typical steps involved in the process of removal and replacement of steam generators.

Emerging regulatory paradigms in glutathione metabolism

PubMed Central

Liu, Yilin; Hyde, Annastasia S.; Simpson, Melanie A.; Barycki, Joseph J.

2015-01-01

One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity, and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer, and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites, and highlight remaining questions about molecular details of the accepted regulatory modes. PMID:24974179

Regulatory landscape for cell therapy--EU view.

PubMed

McBlane, James W

2015-09-01

This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial. A regulation is soon to come into force that will address this and introduce a more efficient clinical trial application process. However, at the marketing authorisation stage, the process is pan-national: the Committee for Human Medicinal Products (CHMP) is responsible for giving the final scientific opinion on all EU marketing authorisation applications for cell therapies: favourable scientific opinions are passed to the European Commission (EC) for further consultation and, if successful, grant of a marketing authorisation valid in all 28 EU countries. In its review of applications for marketing authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the Committee for Advanced Therapies (CAT), who conduct detailed scientific assessments of these applications, with assessment by staff from national regulatory authorities and specialist advisors to the regulators. Copyright © 2015.

Congressional Office of Regulatory Analysis Creation and Sunset and Review Act of 2011

THOMAS, 112th Congress

Rep. Young, Don [R-AK-At Large

2011-01-07

House - 02/08/2011 Referred to the Subcommittee on Regulatory Affairs, Stimulus Oversight and Government Spending . (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Control of regulatory T cell lineage commitment and maintenance.

PubMed

Josefowicz, Steven Z; Rudensky, Alexander

2009-05-01

Foxp3-expressing regulatory T (Treg) cells suppress pathology mediated by immune responses against self and foreign antigens and commensal microorganisms. Sustained expression of the transcription factor Foxp3, a key distinguishing feature of Treg cells, is required for their differentiation and suppressor function. In addition, Foxp3 expression prevents deviation of Treg cells into effector T cell lineages and confers dependence of Treg cell survival and expansion on growth factors, foremost interleukin-2, provided by activated effector T cells. In this review we discuss Treg cell differentiation and maintenance with a particular emphasis on molecular regulation of Foxp3 expression, arguably a key to mechanistic understanding of biology of regulatory T cells.

Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

PubMed

Smith, Jeffrey K

2013-04-01

Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

Safeguards-by-Design:Guidance for High Temperature Gas Reactors (HTGRs) With Prismatic Fuel

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

Mark Schanfein; Casey Durst

2012-11-01

IAEA Design Information Questionnaire (DIQ), prepared by the facility operator, typically with the support of the facility designer. The IAEA will verify design information over the life of the project. This design information is an important IAEA safeguards tool. Since the main interlocutor with the IAEA in each country is the State Regulatory Authority/SSAC (or Regional Regulatory Authority, e.g. EURATOM), the responsibility for conveying this design information to the IAEA falls to the State Regulatory Authority/SSAC. For the nuclear industry to reap the benefits of SBD (i.e. avoid cost overruns and construction schedule slippages), nuclear facility designers and operators should work closely with the State Regulatory Authority and IAEA as soon as a decision is taken to build a new nuclear facility. Ideally, this interaction should begin during the conceptual design phase and continue throughout construction and start-up of a nuclear facility. Such early coordination and planning could influence decisions on the design of the nuclear material processing flow-sheet, material storage and handling arrangements, and facility layout (including safeguards equipment), etc.« less

39 CFR 3020.75 - Review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Review. 3020.75 Section 3020.75 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL PRODUCT LISTS Proposal of the Commission To Modify the Product Lists Described Within the Mail Classification Schedule § 3020.75 Review. The Commission shall review...

Regulatory Enhancements, Infrastructure Modernization, and Connecticut's Interactive, Distance Learning Network.

ERIC Educational Resources Information Center

Pietras, Jesse John

This paper presents an overview of the regulatory, technological, and economic status of interactive distance learning in Connecticut as it relates to the current and future provisioning of services by the telecommunications and cable television industries. The review is predicated upon the following questions: (1) What obligations should the…

Characterization of the evolution of the pharmaceutical regulatory environment.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J

2013-01-01

This paper is part of a research study that is intended to identify pharmaceutical quality risks induced by the ongoing transformation in the industry. This study establishes the current regulatory context by characterizing the development of the pharmaceutical regulatory environment. The regulatory environment is one of the most important external factors that affects a company's organization, processes, and technological strategy. This is especially the case with the pharmaceutical industry, where its products affect the quality of life of the consumers. The quantitative analysis of regulatory events since 1813 and review of the associated literature resulted in identification of six factors influencing the regulatory environment, namely public health protection, public health promotion, crisis management, harmonization, innovation, and modernization. From 1813 to the 1970s the focus of regulators was centered on crisis management and public health protection-a basic mission that has remained consistent over the years. Since the 1980s a gradual move in the regulatory environment towards a greater focus on public health promotion, international harmonization, innovation, and agency modernization may be seen. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities. The impact of these changes on the approaches to quality risk management requires more understanding. The authors are engaged in research to identify elements of the changes that influence pharmaceutical quality. As quality requirements are an integral part of the pharmaceutical regulations, a comprehensive understanding of these regulations is seen as the first step. The results of this study show that (i) public health protection, public health promotion, crisis management, harmonization, innovation, and modernization are factors that affect regulations in the pharmaceutical industry; (ii) the regulators' main

78 FR 30384 - Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... SMALL BUSINESS ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory... Regional (Region X) Small Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National... Region X Regulatory Fairness Board must contact Jos[eacute] M[eacute]ndez by May 30, 2013 in writing, by...

Long Noncoding RNAs: a New Regulatory Code in Metabolic Control

PubMed Central

Zhao, Xu-Yun; Lin, Jiandie D.

2015-01-01

Long noncoding RNAs (lncRNAs) are emerging as an integral part of the regulatory information encoded in the genome. LncRNAs possess the unique capability to interact with nucleic acids and proteins and exert discrete effects on numerous biological processes. Recent studies have delineated multiple lncRNA pathways that control metabolic tissue development and function. The expansion of the regulatory code that links nutrient and hormonal signals to tissue metabolism gives new insights into the genetic and pathogenic mechanisms underlying metabolic disease. This review discusses lncRNA biology with a focus on its role in the development, signaling, and function of key metabolic tissues. PMID:26410599

Regulatory RNAs

PubMed Central

Vazquez-Anderson, Jorge; Contreras, Lydia M

2013-01-01

RNAs have many important functional properties, including that they are independently controllable and highly tunable. As a result of these advantageous properties, their use in a myriad of sophisticated devices has been widely explored. Yet, the exploitation of RNAs for synthetic applications is highly dependent on the ability to characterize the many new molecules that continue to be discovered by large-scale sequencing and high-throughput screening techniques. In this review, we present an exhaustive survey of the most recent synthetic bacterial riboswitches and small RNAs while emphasizing their virtues in gene expression management. We also explore the use of these RNA components as building blocks in the RNA synthetic biology toolbox and discuss examples of synthetic RNA components used to rewire bacterial regulatory circuitry. We anticipate that this field will expand its catalog of smart devices by mimicking and manipulating natural RNA mechanisms and functions. PMID:24356572

Regulatory dendritic cell therapy: from rodents to clinical application.

PubMed

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

2014-10-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulatory dendritic cell therapy: from rodents to clinical application

PubMed Central

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

2014-01-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. PMID:24316407

Information theory in systems biology. Part I: Gene regulatory and metabolic networks.

PubMed

Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali

2016-03-01

"A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strategy for communicating benefit-risk decisions: a comparison of regulatory agencies' publicly available documents

PubMed Central

Leong Wai Yeen, James; Salek, Sam; Walker, Stuart

2014-01-01

The assessment report formats of four major regulatory reference agencies, US Food and Drug Administration, European Medicines Agency, Health Canada, and Australia's Therapeutic Goods Administration were compared to a benefit-risk (BR) documentation template developed by the Centre for Innovation in Regulatory Science and a four-member Consortium on Benefit-Risk Assessment. A case study was also conducted using a US FDA Medical Review, the European Public Assessment Report and Australia's Public Assessment Report for the same product. Compared with the BR Template, existing regulatory report formats are inadequate regarding the listing of benefits and risks, the assigning of relative importance and values, visualization and the utilization of a detailed, systematic, standardized structure. The BR Template is based on the principles of BR assessment common to major regulatory agencies. Given that there are minimal differences among the existing regulatory report formats, it is timely to consider the feasibility of a universal template. PMID:25538620

Regulatory immune cells and functions in autoimmunity and transplantation immunology.

PubMed

Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

2017-05-01

In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

Hybrid imaging worldwide-challenges and opportunities for the developing world: a report of a Technical Meeting organized by IAEA.

PubMed

Kashyap, Ravi; Dondi, Maurizio; Paez, Diana; Mariani, Guliano

2013-05-01

The growth in nuclear medicine, in the past decade, is largely due to hybrid imaging, specifically single-photon emission tomography-computed tomography (SPECT-CT) and positron emission tomography-computed tomography (PET-CT). Introduction and use of hybrid imaging has been growing at a fast pace. This has led to many challenges and opportunities to the personnel dealing with it. The International Atomic Energy Agency (IAEA) keeps a close watch on the trends in applications of nuclear techniques in health by many ways, including obtaining inputs from member states and professional societies. In 2012, a Technical Meeting on trends in hybrid imaging was organized by IAEA to understand the current status and trends of hybrid imaging using nuclear techniques, its role in clinical practice, and associated educational needs and challenges. Perspective of scientific societies and professionals from all the regions of the world was obtained. Heterogeneity in value, educational needs, and access was noted and the drivers of this heterogeneity were discussed. This article presents the key points shared during the technical meeting, focusing primarily on SPECT-CT and PET-CT, and shares the action plan for IAEA to deal with heterogeneity as suggested by the participants. Copyright © 2013 Elsevier Inc. All rights reserved.

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations.

PubMed

Van Eenennaam, Alison L

2013-09-25

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations

PubMed Central

2013-01-01

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

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.

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

Warning letters to sponsor-investigators at academic health centres - the regulatory "canaries in a coal mine".

PubMed

O'Reilly, Erin K; Blair Holbein, M E; Berglund, Jelena P; Parrish, Amanda B; Roth, Mary-Tara; Burnett, Bruce K

2013-12-01

This study highlights Warning Letter (WL) findings issued to sponsor-investigators (S-Is) by the Food and Drug Administration (FDA). The online index of WLs issued from October 1, 2007 through September 30, 2012 was reviewed [1]. Through a manual screening process, letters were evaluated if specifically issued to 'clinical investigators', 'sponsors' or 'sponsor-investigators'. A particular focus was given to S-Is at Academic Health Centres (AHCs). Each letter was scored for the presence of violations in 40 general regulatory categories. A review of FDA WLs issued over a five-year period (FDA Fiscal Years 2008-2012) revealed that WLs to S-Is represent half of the WLs issued to all sponsors (16 of 32 letters). A review of these letters indicates that S-Is are not aware of, or simply do not meet, their regulatory responsibilities as either investigators or sponsors. In comparing total sponsor letters to those of S-Is, the most cited violation was the same: a lack of monitoring. A review of publicly available inspection data indicates that these 16 letters merely represent the tip of the iceberg. This review of the WL database reveals the potential for serious regulatory violations among S-Is at AHCs. Recent translational funding initiatives may serve to increase the number of S-Is, especially among Academic Health Centres (AHCs) [2]; thus, AHCs must become aware of this S-I role and work to support investigators who assume both roles in the course of their research.

Behavioral Economic Laboratory Research in Tobacco Regulatory Science.

PubMed

Tidey, Jennifer W; Cassidy, Rachel N; Miller, Mollie E; Smith, Tracy T

2016-10-01

Research that can provide a scientific foundation for the United States Food and Drug Administration (FDA) tobacco policy decisions is needed to inform tobacco regulatory policy. One factor that affects the impact of a tobacco product on public health is its intensity of use, which is determined, in part, by its abuse liability or reinforcing efficacy. Behavioral economic tasks have considerable utility for assessing the reinforcing efficacy of current and emerging tobacco products. This paper provides a narrative review of several behavioral economic laboratory tasks and identifies important applications to tobacco regulatory science. Behavioral economic laboratory assessments, including operant self-administration, choice tasks and purchase tasks, can be used generate behavioral economic data on the effect of price and other constraints on tobacco product consumption. These tasks could provide an expedited simulation of the effects of various tobacco control policies across populations of interest to the FDA. Tobacco regulatory research questions that can be addressed with behavioral economic tasks include assessments of the impact of product characteristics on product demand, assessments of the abuse liability of novel and potential modified risk tobacco products (MRTPs), and assessments of the impact of conventional and novel products in vulnerable populations.

Major regulatory mechanisms involved in sperm motility

PubMed Central

Pereira, Rute; Sá, Rosália; Barros, Alberto; Sousa, Mário

2017-01-01

The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies. PMID:26680031

75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

Data Integrity-A Study of Current Regulatory Thinking and Action.

PubMed

Shafiei, Nader; De Montardy, Regis; Rivera-Martinez, Edwin

2015-01-01

In reaction to breaches of data integrity in the pharmaceutical industry, regulatory authorities have introduced inspection approaches or initiatives with the aim of reducing occurrences of data integrity problems. This review article-based on study of 65 cases of regulatory action from 2002 to 2014-provides an overview of current regulatory thinking and action on breaches of data integrity affecting GxP (health-related regulations) processes supporting non-clinical studies, clinical studies, laboratory controls, and production controls. These case studies largely represent position of the U.S. Food and Drug Administration and the regulatory agencies affiliated with the European Medicines Agency. Also discussed is the role of human factors as a potential source of data integrity problems. The article concludes by recommending some remedial controls that could be established to avoid or reduce occurrences of data integrity problems.Lay Abstract: In fulfilling their mission to protect public health, regulatory agencies (e.g., U.S. Food and Drug Administration, European Medicines Agency) must establish confidence that medical products they approve are fit for their intended use. In so doing they rely on scientific and operational data generated during research, development, manufacturing, sales, marketing, distribution, and post-marketing surveillance activities. The level of confidence they build is directly proportional to the scientific validity and integrity of data presented to them by the sponsors of medical products. In this article we present analysis of 65 case studies that document regulatory action taken by various regulatory agencies on breach of data integrity between 2002 and 2014. The ensuing discussion on current trends largely represents position of the U.S. Food and Drug Administration and European Medicines Agency. The article concludes by proposing some remedial controls that could be established by pharmaceutical companies to avoid or reduce

Nuclear Regulatory Commission issuances, September 1995. Volume 42, Number 3

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

NONE

This book contains an issuance of the Atomic Safety and Licensing Board and a Director`s Decision, both of the US Nuclear Regulatory Commission. The issuance concerns the dismissal of a case by adopting a settlement reached by the Staff of the Nuclear Regulatory Commission and a Radiation Safety Officer of a hospital in which the safety officer pled guilty to deliberate misconduct. The Director`s Decision was to deny a petition to impose a fine on Tennessee Valley Authority concerning alleged harassment of the petitioner and to appoint an independent arbitration board to review all past complaints filed against TVA concerningmore » the Watts Bar Nuclear Plant.« less

Helminth-induced regulatory T cells and suppression of allergic responses.

PubMed

Logan, Jayden; Navarro, Severine; Loukas, Alex; Giacomin, Paul

2018-05-28

Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, and clinical trials with live worm infections, discussing the therapeutic potential for worms and their secreted products for treating allergic inflammation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

R-Matrix Codes for Charged-Particle Induced Reactions in the Resolved Resonance Region (3), Summary Report of an IAEA Consultants' Meeting IAEA Headquarters, Vienna, Austria, 28-30 June 2017

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

Leeb, Helmut; Dimitriou, Paraskevi; Thompson, Ian

A Consultants Meeting was held at the IAEA Headquarters, from 28 to 30 June 2017, to discuss the results of a test exercise that had been defined and assigned to all participants of the previous meeting held in December 2016. Five codes were used in this exercise: AMUR, AZURE2, RAC, SFRESCO and SAMMY. The results obtained from these codes were compared and further actions were proposed. Participants’ presentations and technical discussions, as well as proposed additional actions have been summarized in this report.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

PubMed

Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

PubMed Central

Hovingh, Elise S.; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed. PMID:28066340

Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

PubMed

Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

2017-08-01

Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC)...

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.

PubMed

Vierstra, Jeff; Rynes, Eric; Sandstrom, Richard; Zhang, Miaohua; Canfield, Theresa; Hansen, R Scott; Stehling-Sun, Sandra; Sabo, Peter J; Byron, Rachel; Humbert, Richard; Thurman, Robert E; Johnson, Audra K; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Giste, Erika; Haugen, Eric; Dunn, Douglas; Wilken, Matthew S; Josefowicz, Steven; Samstein, Robert; Chang, Kai-Hsin; Eichler, Evan E; De Bruijn, Marella; Reh, Thomas A; Skoultchi, Arthur; Rudensky, Alexander; Orkin, Stuart H; Papayannopoulou, Thalia; Treuting, Piper M; Selleri, Licia; Kaul, Rajinder; Groudine, Mark; Bender, M A; Stamatoyannopoulos, John A

2014-11-21

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes. Copyright © 2014, American Association for the Advancement of Science.

76 FR 12769 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...,\\2\\ notice is hereby given that on February 16, 2011, the Financial Industry Regulatory Authority... CFR 240.19b-4(f)(3). I. Self-Regulatory Organization's Statement of the Terms of Substance of the...

A systematic analysis of a mi-RNA inter-pathway regulatory motif

PubMed Central

2013-01-01

Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805

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.

Approach to training of personnel to manage radioactive wastes offered by education training Centre at Moscow Sia Radon under sponsorship of IAEA

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

Batyukhnova, O.G.; Dmitriev, S.A.; Ojovan, M.I.

The availability of qualified personnel is crucial to the licensing and efficient and safe operation of waste management facilities and for the improvement of the existing waste management practices. The countries with some degree of waste management activities are of special concerns, since their narrow waste management experience and personal capabilities may be a limiting factor to manage radioactive waste in a safe and technically optimal manner. The International Education Training Centre (IETC) at Moscow State Unitary Enterprise Scientific and Industrial Association 'Radon' (SIA 'Radon'), in co-operation with the International Atomic Energy Agency (IAEA), has developed expertise and provided trainingmore » to waste management personnel for the last 10 years. During this period, more than 300 specialists from 26 European and Asian countries, (mostly) sponsored by the IAEA, have increased their knowledge and skills in radioactive waste management. The current experience of the SIA 'Radon' in the organisation of the IAEA sponsored training is summarized and an outline of some strategic educational elements, which IETC will continue to pursue in the coming years, is provided. (authors)« less

A dosimetry study comparing NCS report-5, IAEA TRS-381, AAPM TG-51 and IAEA TRS-398 in three clinical electron beam energies

NASA Astrophysics Data System (ADS)

Palmans, Hugo; Nafaa, Laila; de Patoul, Nathalie; Denis, Jean-Marc; Tomsej, Milan; Vynckier, Stefaan

2003-05-01

New codes of practice for reference dosimetry in clinical high-energy photon and electron beams have been published recently, to replace the air kerma based codes of practice that have determined the dosimetry of these beams for the past twenty years. In the present work, we compared dosimetry based on the two most widespread absorbed dose based recommendations (AAPM TG-51 and IAEA TRS-398) with two air kerma based recommendations (NCS report-5 and IAEA TRS-381). Measurements were performed in three clinical electron beam energies using two NE2571-type cylindrical chambers, two Markus-type plane-parallel chambers and two NACP-02-type plane-parallel chambers. Dosimetry based on direct calibrations of all chambers in 60Co was investigated, as well as dosimetry based on cross-calibrations of plane-parallel chambers against a cylindrical chamber in a high-energy electron beam. Furthermore, 60Co perturbation factors for plane-parallel chambers were derived. It is shown that the use of 60Co calibration factors could result in deviations of more than 2% for plane-parallel chambers between the old and new codes of practice, whereas the use of cross-calibration factors, which is the first recommendation in the new codes, reduces the differences to less than 0.8% for all situations investigated here. The results thus show that neither the chamber-to-chamber variations, nor the obtained absolute dose values are significantly altered by changing from air kerma based dosimetry to absorbed dose based dosimetry when using calibration factors obtained from the Laboratory for Standard Dosimetry, Ghent, Belgium. The values of the 60Co perturbation factor for plane-parallel chambers (katt . km for the air kerma based and pwall for the absorbed dose based codes of practice) that are obtained from comparing the results based on 60Co calibrations and cross-calibrations are within the experimental uncertainties in agreement with the results from other investigators.

[Regulatory T cells].

PubMed

Marinić, Igor; Gagro, Alenka; Rabatić, Sabina

2006-12-01

Regulatory T-cells are a subset of T cells that have beene extensively studied in modern immunology. They are important for the maintenance of peripheral tolerance, and have an important role in various clinical conditions such as allergy, autoimmune disorders, tumors, infections, and in transplant medicine. Basically, this population has a suppressive effect on the neighboring immune cells, thus contributing to the local modulation and control of immune response. There are two main populations of regulatory T cells - natural regulatory T cells, which form a distinct cellular lineage, develop in thymus and perform their modulatory action through direct intercellular contact, along with the secreted cytokines; and inducible regulatory T cells, which develop in the periphery after contact with the antigen that is presented on the antigen presenting cell, and their primary mode of action is through the interleukin 10 (IL-10) and transforming growth factor beta (TGF-alpha) cytokines. Natural regulatory T cells are activated through T cell receptor after contact with specific antigen and inhibit proliferation of other T cells in an antigen independent manner. One of the major difficulties in the research of regulatory T cells is the lack of specific molecular markers that would identify these cells. Natural regulatory T cells constitutively express surface molecule CD25, but many other surface and intracellular molecules (HLA-DR, CD122, CD45RO, CD62, CTLA-4, GITR, PD-1, Notch, FOXP3, etc.) are being investigated for further phenotypic characterization of these cells. Because regulatory T cells have an important role in establishing peripheral tolerance, their importance is manifested in a number of clinical conditions. In the IPEX syndrome (immunodysregulation, polyendocrinopathy and enteropathy, X-linked), which is caused by mutation in Foxp3 gene that influences the development and function of regulatory T cells, patients develop severe autoimmune reactions that

Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

PubMed

Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

2016-01-01

Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

Food irradiation—US regulatory considerations

NASA Astrophysics Data System (ADS)

Morehouse, Kim M.

2002-03-01

The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

Human System Integration: Regulatory Analysis

NASA Technical Reports Server (NTRS)

2005-01-01

This document was intended as an input to the Access 5 Policy Integrated Product team. Using a Human System Integration (HIS) perspective, a regulatory analyses of the FARS (specifically Part 91), the Airman s Information Manual (AIM) and the FAA Controllers Handbook (7110.65) was conducted as part of a front-end approach needed to derive HSI requirements for Unmanned Aircraft Systems (UAS) operations in the National Airspace System above FL430. The review of the above aviation reference materials yielded eighty-four functions determined to be necessary or highly desirable for flight within the Air Traffic Management System. They include categories for Flight, Communications, Navigation, Surveillance, and Hazard Avoidance.

Redesigning the Regulatory Framework for Ambulatory Care Services in New York

PubMed Central

Chokshi, Dave A; Rugge, John; Shah, Nirav R

2014-01-01

Context While hospitals remain important centers of gravity in the health system, services are increasingly being delivered through ambulatory care. This shift to ambulatory care is giving rise to new delivery structures, such as retail clinics and urgent care centers, as well as reinventing existing ambulatory care capacity, as seen with the patient-centered medical home model and the movement toward team-based care. To protect the public's interests, oversight of ambulatory care services must keep pace with these rapid changes. With this purpose, in January 2013 the New York Public Health and Health Planning Council undertook a redesign of the regulatory framework for the state's ambulatory care services. This article describes the principles undergirding the framework as well as the regulatory recommendations themselves. Methods We explored and analyzed the regulation of ambulatory care services in New York in accordance with the available gray and peer-reviewed literature and legislative documents. The deliberations of the Public Health and Health Planning Council informed our review. Findings The vision of high-performing ambulatory care should be rooted in the Triple Aim (better health, higher-quality care, lower costs), with a particular emphasis on continuity of care for patients. There is a pressing need to better define the taxonomy of ambulatory care services. From the state government's perspective, this clarification requires better reporting from new health care entities (eg, retail clinics), connections with regional and state health information technology hubs, and coordination among state agencies. A uniform nomenclature also would improve consumers’ understanding of rights and responsibilities. Finally, the regulatory mechanisms employed—from mandatory reporting to licensure to regional planning to the certificate of need—should remain flexible and match the degree of consensus regarding the appropriate regulatory path. Conclusions Few other

Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices

PubMed Central

Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

2015-01-01

While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of

10 CFR 12.309 - Judicial review.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Judicial review. 12.309 Section 12.309 Energy NUCLEAR REGULATORY COMMISSION IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT IN AGENCY PROCEEDINGS Procedures for Considering Applications § 12.309 Judicial review. Judicial review of final agency decisions on awards may be...

10 CFR 110.40 - Commission review.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Commission review. 110.40 Section 110.40 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Review of License Applications § 110.40 Commission review. (a) Immediately after receipt of a license application for an export...

10 CFR 110.40 - Commission review.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Commission review. 110.40 Section 110.40 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Review of License Applications § 110.40 Commission review. (a) Immediately after receipt of a license application for an export...

10 CFR 110.40 - Commission review.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Commission review. 110.40 Section 110.40 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Review of License Applications § 110.40 Commission review. (a) Immediately after receipt of a license application for an export...

Regulatory roles of mast cells in immune responses.

PubMed

Morita, Hideaki; Saito, Hirohisa; Matsumoto, Kenji; Nakae, Susumu

2016-09-01

Mast cells are important immune cells for host defense through activation of innate immunity (via toll-like receptors or complement receptors) and acquired immunity (via FcεRI). Conversely, mast cells also act as effector cells that exacerbate development of allergic or autoimmune disorders. Yet, several lines of evidence show that mast cells act as regulatory cells to suppress certain inflammatory diseases. Here, we review the mechanisms by which mast cells suppress diseases.

Weight of evidence approaches for the identification of endocrine disrupting properties of chemicals: Review and recommendations for EU regulatory application.

PubMed

Gross, Melanie; Green, Richard M; Weltje, Lennart; Wheeler, James R

2017-12-01

A Weight-of-evidence (WoE) evaluation should be applied in assessing all the available data for the identification of endocrine disrupting (ED) properties of chemicals. The European Commission draft acts specifying criteria under the biocidal products and plant protection products regulations require that WoE is implemented for the assessment of such products. However, only some general considerations and principles of how a WoE should be conducted are provided. This paper reviews WoE approaches to distil key recommendations specifically for the evaluation of potential ED properties of chemicals. In a manner, which is consistent with existing, published WoE frameworks, the WoE evaluation of ED properties can be divided into four phases: 1) Definition of causal questions and data gathering and selection, 2) Review of individual studies, 3) Data integration and evaluation, and 4) Drawing conclusions based on inferences. Recommendations are made on how to conduct each phase robustly and transparently to help guide the WoE evaluation of potential endocrine disrupting properties of chemicals within a European regulatory context. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Patient Preferences in Regulatory Benefit-Risk Assessments: A US Perspective.

PubMed

Johnson, F Reed; Zhou, Mo

Demands for greater transparency in US regulatory assessments of benefits and risks, together with growing interest in engaging patients in Food and Drug Administration regulatory decision making, have resulted in several recent regulatory developments. Although Food and Drug Administration's Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH) have established patient-engagement initiatives, CDRH has proposed guidelines for considering quantitative data on patients' benefit-risk perspectives, while CDER has focused on a more qualitative approach. We summarize two significant studies that were developed in collaboration and consultation with CDER and CDRH. CDER encouraged a patient advocacy group to propose draft guidance on engaging patient and caregiver stakeholders in regulatory decision making for Duchenne muscular dystrophy. CDRH sponsored a discrete-choice experiment case study to quantify obese respondents' perspectives on "meaningful benefits." CDRH and CDER issued draft guidance in May and June 2015, respectively, on including patient-preference data in regulatory submissions. Both organizations face challenges. CDER is working on integrating qualitative data into existing evidence-based review processes and is exploring options for therapeutic areas not included on a priority list. CDRH has adopted an approach that requires patient-preference data to satisfy standards of valid scientific evidence. Although that strategy could facilitate integrating patient perspectives directly with clinical data on benefits and harms, generating such data requires building capacity. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Improving food environments and tackling obesity: A realist systematic review of the policy success of regulatory interventions targeting population nutrition

PubMed Central

Sisnowski, Jana; Merlin, Tracy

2017-01-01

Background This systematic review (PROSPERO: CRD42015025276) employs a realist approach to investigate the effect of “real-world” policies targeting different aspects of the food environment that shape individual and collective nutrition. Objectives We were interested in assessing intermediate outcomes along the assumed causal pathway to “policy success”, in addition to the final outcome of changed consumption patterns. Data sources We performed a search of 16 databases through October 2015, with no initial restriction by language. Study eligibility criteria We included all publications that reported the effect of statutory provisions aimed at reducing the consumption of energy-dense foods and beverages in the general population. We allowed all methodological approaches that contained some measure of comparison, including studies of implementation progress. Study appraisal and synthesis methods We reviewed included studies using the appraisal tools for pre-post and observational studies developed by the National Heart, Lung, and Blood Institute. Given the considerable heterogeneity in interventions assessed, study designs employed, and outcome measures reported, we opted for a narrative synthesis of results. Results and implications Results drawn from 36 peer-reviewed articles and grey literature reports demonstrated that isolated regulatory interventions can improve intermediate outcomes, but fail to affect consumption at clinically significant levels. The included literature covered six different types of interventions, with 19 studies reporting on calorie posting on chain restaurant menus. The large majority of the identified interventions were conducted in the US. Early results from recent taxation measures were published after the review cut-off date but these suggested more favorable effects on consumption levels. Nevertheless, the evidence assessed in this review suggests that current policies are generally falling short of anticipated health impacts

76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

Radiation processing of natural polymers: The IAEA contribution

NASA Astrophysics Data System (ADS)

Haji-Saeid, Mohammad; Safrany, Agnes; Sampa, Maria Helena de O.; Ramamoorthy, Natesan

2010-03-01

Radiation processing offers a clean and additive-free method for preparation of value-added novel materials based on renewable, non-toxic, and biodegradable natural polymers. Crosslinked natural polymers can be used as hydrogel wound dressings, face cleaning cosmetic masks, adsorbents of toxins, and non-bedsore mats; while low molecular weight products show antibiotic, antioxidant, and plant-growth promoting properties. Recognizing the potential benefits that radiation technology can offer for processing of natural polymers into useful products, the IAEA implemented a coordinated research project (CRP) on "Development of Radiation-processed products of Natural Polymers for application in Agriculture, Healthcare, Industry and Environment". This CRP was launched at the end of 2007 with participation of 16 MS to help connecting radiation technology and end-users to derive enhanced benefits from these new value-added products of radiation-processed natural materials. In this paper the results of activities in participating MS related to this work will be presented.

Total Risk Integrated Methodology (TRIM) - Peer Review and Publications

EPA Pesticide Factsheets

Peer review: Consistent with Agency peer review policy, and the 1994 Agency Task Force on Environmental Regulatory Modeling, internal and external peer review has been an integral part of the TRIM development plan.

Regulatory factors governing adenosine-to-inosine (A-to-I) RNA editing.

PubMed

Hong, HuiQi; Lin, Jaymie Siqi; Chen, Leilei

2015-03-31

Adenosine-to-inosine (A-to-I) RNA editing, the most prevalent mode of transcript modification in higher eukaryotes, is catalysed by the adenosine deaminases acting on RNA (ADARs). A-to-I editing imposes an additional layer of gene regulation as it dictates various aspects of RNA metabolism, including RNA folding, processing, localization and degradation. Furthermore, editing events in exonic regions contribute to proteome diversity as translational machinery decodes inosine as guanosine. Although it has been demonstrated that dysregulated A-to-I editing contributes to various diseases, the precise regulatory mechanisms governing this critical cellular process have yet to be fully elucidated. However, integration of previous studies revealed that regulation of A-to-I editing is multifaceted, weaving an intricate network of auto- and transregulations, including the involvement of virus-originated factors like adenovirus-associated RNA. Taken together, it is apparent that tipping of any regulatory components will have profound effects on A-to-I editing, which in turn contributes to both normal and aberrant physiological conditions. A complete understanding of this intricate regulatory network may ultimately be translated into new therapeutic strategies against diseases driven by perturbed RNA editing events. Herein, we review the current state of knowledge on the regulatory mechanisms governing A-to-I editing and propose the role of other co-factors that may be involved in this complex regulatory process.

Patients come from populations and populations contain patients. A two-stage scientific and ethics review: The next adaptation for single institutional review boards.

PubMed

Knopman, David; Alford, Eli; Tate, Kaitlin; Long, Mark; Khachaturian, Ara S

2017-08-01

For nearly 50 years, institutional review boards (IRB) and independent ethics committees have featured local oversight as a core function of research ethics reviews. However growing complexity in Alzheimer's clinical research suggests current approaches to research volunteer safety is hampering development of new therapeutics. As a partial response to this challenge, the NIH has mandated that all NIH-funded multi-site studies will use a single Institutional Review Board. The perspective describes a joint program to provide a single IRB of record (sIRB) for phases of multi-site studies. The approach follows two steps. One, an expert Scientific Review Committee (SRC) of senior researchers in the field will conduct the review principally of scientific merit, significance, feasibility, and the likelihood of meaningful results. The second step will be the IRB's regulatory and ethics review. The IRB will apply appropriate regulatory criteria for approval including minimization of risks to subjects and risks reasonable in relation to anticipated benefits, equitable subject selection, informed consent, protections for vulnerable populations, and application of local context considerations, among others. There is a steady demand for scientific, ethical and regulatory review of planned Alzheimer's studies. As of January 15, 2017, there are nearly 400 open studies, Phase II and III, industry and NIH sponsored trials on disease indications affecting memory, movement and mood in the US. The effort will initially accept protocols for studies of Alzheimer's disease, dementia, and related disorders effecting memory, movement and mood. Future aims will be to provide scientific review and, where applicable, regulatory and ethical review in an international context outside North America with sites possibly in Asia, Europe and Australia. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

77 FR 43620 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... self-regulatory organization consents, the Commission shall either approve the proposed rule change...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to the Handling of Stop and Stop Limit...

75 FR 75969 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

.... ACTION: Comment request. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management Services, Office of Management invites comments on the submission for OMB..., Regulatory Information Management Services, Office of Management. Federal Student Aid Type of Review...

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

PubMed

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

78 FR 27169 - Regulatory Flexibility Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Chapter... parts 174, 177, 191, and 192... 2013 2014 Transportation of Natural and Other Gas by Pipeline; Annual... review of some of 49 CFR parts 106, 107, 171. The full analysis document for the hazardous materials...

A critical assessment of regulatory triggers for products of biotechnology: Product vs. process

PubMed Central

McHughen, Alan

2016-01-01

ABSTRACT Regulatory policies governing the safety of genetic engineering (rDNA) and the resulting products (GMOs) have been contentious and divisive, especially in agricultural applications of the technologies. These tensions led to vastly different approaches to safety regulation in different jurisdictions, even though the intent of regulations—to assure public and environmental safety—are common worldwide, and even though the international scientific communities agree on the basic principles of risk assessment and risk management. So great are the political divisions that jurisdictions cannot even agree on the appropriate triggers for regulatory capture, whether product or process. This paper reviews the historical policy and scientific implications of agricultural biotechnology regulatory approaches taken by the European Union, USA and Canada, using their respective statutes and regulations, and then critically assesses the scientific underpinnings of each. PMID:27813691

A critical assessment of regulatory triggers for products of biotechnology: Product vs. process.

PubMed

McHughen, Alan

2016-10-01

Regulatory policies governing the safety of genetic engineering (rDNA) and the resulting products (GMOs) have been contentious and divisive, especially in agricultural applications of the technologies. These tensions led to vastly different approaches to safety regulation in different jurisdictions, even though the intent of regulations-to assure public and environmental safety-are common worldwide, and even though the international scientific communities agree on the basic principles of risk assessment and risk management. So great are the political divisions that jurisdictions cannot even agree on the appropriate triggers for regulatory capture, whether product or process. This paper reviews the historical policy and scientific implications of agricultural biotechnology regulatory approaches taken by the European Union, USA and Canada, using their respective statutes and regulations, and then critically assesses the scientific underpinnings of each.

Telemental Health for Children and Adolescents: An Overview of Legal, Regulatory, and Risk Management Issues.

PubMed

Kramer, Gregory M; Luxton, David D

2016-04-01

The use of technology to provide telemental healthcare continues to increase; however, little has been written about the legal and regulatory issues involved in providing this form of care to children and adolescents. This article reviews existing laws and regulations to summarize the risk management issues relevant to providing telemental healthcare to children and adolescents. There are several legal and regulatory areas in which telemental health clinicians need to have awareness. These areas include: 1) Licensure, 2) malpractice liability, 3) credentialing and privileging, 4) informed consent, 5) security and privacy, and 6) emergency management. Although legal and regulatory challenges remain in providing telemental healthcare to children and adolescents, it is possible to overcome these challenges with knowledge of the issues and appropriate risk management strategies. We provide general knowledge of these key legal and regulatory issues, along with some risk management recommendations.

Patient safety and efficacy as measured by clinical trials and regulatory policy.

PubMed

Harvey, B E; Alpert, S

1997-01-01

Virtual Reality and other technological innovations in medicine provide new challenges to the regulatory framework of the premarket review process for medical devices. By reinventing the government-academia-industry partnership, clinical trial data necessary for a medical device to enter the market can be more efficiently obtained.

75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

76 FR 25397 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the By- Laws of FINRA Regulation, Inc. With Regard to District Committees April 28, 2011. I. Introduction On February 25, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

WE-AB-213-04: IAEA Support to Medical Physics in Africa and Latin America: Achievements and Challenges

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

Meghzifene, A.

AAPM projects and collaborations in Africa Adam Shulman (AA-SC Chair) The African Affairs Subcommittee (AA-SC) of the AAPM will present a multi-institutional approach to medical physics support in Africa. Current work to increase the quality of care and level of safety for the medical physics practice in Senegal, Ghana, and Zimbabwe will be presented, along with preliminary projects in Nigeria and Botswana. Because the task of addressing the needs of medical physics in countries across Africa is larger than one entity can accomplish on its own, the AA-SC has taken the approach of joining forces with multiple organizations such asmore » Radiating Hope and TreatSafely (NGO’s), the IAEA, companies like BrainLab, Varian and Elekta, medical volunteers and academic institutions such as NYU and Washington University. Elements of current projects include: 1) Distance training and evaluation of the quality of contouring and treatment planning, teaching treatment planning and other subjects, and troubleshooting using modern telecommunications technology in Senegal, Ghana, and Zimbabwe; 2) Assistance in the transition from 2D to 3D in Senegal and Zimbabwe; 3) Assistance in the transition from 3D to IMRT using in-house compensators in Senegal; 4) Modernizing the cancer center in Senegal and increasing safety and; 5) Training on on 3D techniques in Ghana; 6) Assisting a teaching and training radiation oncology center to be built in Zimbabwe; 7) Working with the ISEP Program in Sub-Saharan Africa; 8) Creating instructional videos on linac commissioning; 9) Working on a possible collaboration to train physicists in Nigeria. Building on past achievements, the subcommittee seeks to make a larger impact on the continent, as the number and size of projects increases and more human resources become available. The State of Medical Physics Collaborations and Projects in Latin America Sandra Guzman (Peru) The lack of Medical Physicists (MP) in many Latin American (LA) countries leads

75 FR 13105 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

... DEPARTMENT OF EDUCATION Submission for OMB Review; Comment Request AGENCY: Department of Education. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management... 19, 2010. ADDRESSES: Written comments should be addressed to the Office of Information and Regulatory...

75 FR 12219 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... DEPARTMENT OF EDUCATION Submission for OMB Review; Comment Request AGENCY: Department of Education. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management... 14, 2010. ADDRESSES: Written comments should be addressed to the Office of Information and Regulatory...

75 FR 32164 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

... DEPARTMENT OF EDUCATION Submission for OMB Review; Comment Request AGENCY: Department of Education. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management... 7, 2010. ADDRESSES: Written comments should be addressed to the Office of Information and Regulatory...

75 FR 13733 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... DEPARTMENT OF EDUCATION Submission for OMB Review; Comment Request AGENCY: Department of Education. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management... 22, 2010. ADDRESSES: Written comments should be addressed to the Office of Information and Regulatory...

75 FR 22759 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... DEPARTMENT OF EDUCATION Submission for OMB Review; Comment Request AGENCY: Department of Education. SUMMARY: The Acting Director, Information Collection Clearance Division, Regulatory Information Management... 1, 2010. ADDRESSES: Written comments should be addressed to the Office of Information and Regulatory...

Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

PubMed

Bowman, Diana M; Gatof, Jake

2015-01-01

Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.

75 FR 6422 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Incorporated NYSE Rule 411(a)(ii)(5) as Part of the Process of Developing the Consolidated FINRA Rulebook February 2, 2010. On December 4, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research.

PubMed

Miyagaki, Tomomitsu; Fujimoto, Manabu; Sato, Shinichi

2015-10-01

B cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause inflammatory and autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of inflammatory and autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human inflammatory and autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in animal models of inflammatory and autoimmune diseases and in clinical research using human samples. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Translating New Science Into the Drug Review Process

PubMed Central

Rouse, Rodney; Kruhlak, Naomi; Weaver, James; Burkhart, Keith; Patel, Vikram; Strauss, David G.

2017-01-01

In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER) review process and close the gap between scientific innovation and drug review. The Division, located in the Office of Clinical Pharmacology, is unique in that it performs mission-critical applied research and review across the translational research spectrum including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine, and postmarket analyses. The Division collaborates with Offices throughout CDER, across the FDA, other government agencies, academia, and industry. The Division is able to rapidly form interdisciplinary teams of pharmacologists, biologists, chemists, computational scientists, and clinicians to respond to challenging regulatory questions for specific review issues and for longer-range projects requiring the development of predictive models, tools, and biomarkers to speed the development and regulatory evaluation of safe and effective drugs. This article reviews the Division’s recent work and future directions, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine. PMID:29568713

10 CFR 7.16 - Annual comprehensive review.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Annual comprehensive review. 7.16 Section 7.16 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.16 Annual comprehensive review. (a) The Chairman of the Commission shall conduct an annual comprehensive review of the activities and responsibilities of...

10 CFR 7.16 - Annual comprehensive review.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Annual comprehensive review. 7.16 Section 7.16 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.16 Annual comprehensive review. (a) The Chairman of the Commission shall conduct an annual comprehensive review of the activities and responsibilities of...

10 CFR 7.16 - Annual comprehensive review.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Annual comprehensive review. 7.16 Section 7.16 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.16 Annual comprehensive review. (a) The Chairman of the Commission shall conduct an annual comprehensive review of the activities and responsibilities of...

10 CFR 7.16 - Annual comprehensive review.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Annual comprehensive review. 7.16 Section 7.16 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.16 Annual comprehensive review. (a) The Chairman of the Commission shall conduct an annual comprehensive review of the activities and responsibilities of...

10 CFR 7.16 - Annual comprehensive review.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Annual comprehensive review. 7.16 Section 7.16 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.16 Annual comprehensive review. (a) The Chairman of the Commission shall conduct an annual comprehensive review of the activities and responsibilities of...

Redesigning the regulatory framework for ambulatory care services in New York.

PubMed

Chokshi, Dave A; Rugge, John; Shah, Nirav R

2014-12-01

Policy Points: The landscape of ambulatory care services in the United States is rapidly changing on account of payment reform, primary care transformation, and the rise of convenient care options such as retail clinics. New York State has undertaken a redesign of regulatory policy for ambulatory care rooted in the Triple Aim (better health, higher-quality care, lower costs)-with a particular emphasis on continuity of care for patients. Key tenets of the regulatory approach include defining and tracking the taxonomy of ambulatory care services as well as ensuring that convenient care options do not erode continuity of care for patients. While hospitals remain important centers of gravity in the health system, services are increasingly being delivered through ambulatory care. This shift to ambulatory care is giving rise to new delivery structures, such as retail clinics and urgent care centers, as well as reinventing existing ambulatory care capacity, as seen with the patient-centered medical home model and the movement toward team-based care. To protect the public's interests, oversight of ambulatory care services must keep pace with these rapid changes. With this purpose, in January 2013 the New York Public Health and Health Planning Council undertook a redesign of the regulatory framework for the state's ambulatory care services. This article describes the principles undergirding the framework as well as the regulatory recommendations themselves. We explored and analyzed the regulation of ambulatory care services in New York in accordance with the available gray and peer-reviewed literature and legislative documents. The deliberations of the Public Health and Health Planning Council informed our review. The vision of high-performing ambulatory care should be rooted in the Triple Aim (better health, higher-quality care, lower costs), with a particular emphasis on continuity of care for patients. There is a pressing need to better define the taxonomy of ambulatory

75 FR 21805 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... FR Cite NPRM 08/00/10 NPRM Comment Period End 10/00/10 Regulatory Flexibility Analysis Required: Yes... pursuant to the requirements of the Chief Financial Officers Act of 1990 (CFO Act), 31 U.S.C. 901-03. The CFO Act requires each agency's chief financial officer (CFO) to ``review, on a biennial basis, the...

Site Variability in Regulatory Oversight for an International Study of Pediatric Sepsis.

PubMed

Michelson, Kelly N; Reubenson, Gary; Weiss, Scott L; Fitzgerald, Julie C; Ackerman, Kate K; Christie, LeeAnn; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Schreiner, Mark S

2018-04-01

Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. Survey. Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. None. Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). Variability in regulatory oversight was evident for

Current FDA regulatory guidance on the conduct of drug discrimination studies for NDA review: Does the scientific literature support recent recommendations?

PubMed

Gauvin, David V; Zimmermann, Zachary J; Kallman, Mary Jeanne

2016-11-01

The Controlled Substances Staff of the Center for Drug Evaluation and Research at the US Food and Drug Administration and the Pharmaceutical Research Manufacturers Association (PhRMA) conducted a series of open forum dialog sessions between 2006 and 2016. A Cross Company Abuse Liability Council (CCALC) was formed during the process of this unique collaborative effort between Industry and Federal Regulators whose goals were to establish the development of standards for the preclinical screening of new molecular entities for schedule control actions required as part of every New Drug Application process. The draft guidance document was published and disseminated in 2010, which allowed for alternative approaches to each study protocol requirement needed for NDA review, if the approach satisfied the requirements of the applicable statutes and regulations (i.e., the controlled substance act). In a series of recent pre-study protocol reviews requested by confidential Pharmaceutical Sponsors of MPI Research, the CSS staff appeared to change its policy and set forth to require all drug discrimination study data to be generated under "extinction" test sessions. MPI Research is a Contract Research Organization acting on behalf of pharmaceutical companies and bound under separate confidentiality agreements. The purpose of this review is to highlight the data appearing in peer-reviewed scientific journals that do not support the regulatory administrative constraints on one specific testing methodology (extinction) to the exclusion of another (reinforced test sessions). This mind shift represents a restrictive administrative policy by the FDA that is not supported by the published data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nanomaterial categorization for assessing risk potential to facilitate regulatory decision-making.

PubMed

Godwin, Hilary; Nameth, Catherine; Avery, David; Bergeson, Lynn L; Bernard, Daniel; Beryt, Elizabeth; Boyes, William; Brown, Scott; Clippinger, Amy J; Cohen, Yoram; Doa, Maria; Hendren, Christine Ogilvie; Holden, Patricia; Houck, Keith; Kane, Agnes B; Klaessig, Frederick; Kodas, Toivo; Landsiedel, Robert; Lynch, Iseult; Malloy, Timothy; Miller, Mary Beth; Muller, Julie; Oberdorster, Gunter; Petersen, Elijah J; Pleus, Richard C; Sayre, Philip; Stone, Vicki; Sullivan, Kristie M; Tentschert, Jutta; Wallis, Philip; Nel, Andre E

2015-01-01

For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.

Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA.

PubMed

Tani, Hidenori

2017-03-22

Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although the importance of lncRNAs has been documented in previous reports, the biological and physiological functions of lncRNAs remain largely unknown. The role of lncRNAs seems an elusive problem. Here, I propose a clue to the identification of regulatory lncRNAs. The key point is RNA half-life. RNAs with a long half-life (t 1/2 > 4 h) contain a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t 1/2 < 4 h) include known regulatory ncRNAs and regulatory mRNAs. This novel class of ncRNAs with a short half-life can be categorized as Short-Lived non-coding Transcripts (SLiTs). I consider that SLiTs are likely to be rich in functionally uncharacterized regulatory RNAs. This review describes recent progress in research into SLiTs.

12 CFR 562.2 - Regulatory reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

76 FR 32331 - Preliminary Plan for Retrospective Review of Existing Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... review. In addition, DHS launched an IdeaScale Web page; this social media tool provided an additional... agency's regulatory program more effective or less burdensome in achieving its regulatory objectives. DHS...

Zone of Polarizing Activity Regulatory Sequence Mutations/Duplications with Preaxial Polydactyly and Longitudinal Preaxial Ray Deficiency in the Phenotype: A Review of Human Cases, Animal Models, and Insights Regarding the Pathogenesis

PubMed Central

2018-01-01

Clinicians and scientists interested in developmental biology have viewed preaxial polydactyly (PPD) and longitudinal preaxial ray deficiency (LPAD) as two different entities. Point mutations and duplications in the zone of polarizing activity regulatory sequence (ZRS) are associated with anterior ectopic expression of Sonic Hedgehog (SHH) in the limb bud and usually result in a PPD phenotype. However, some of these mutations/duplications also have LPAD in the phenotype. This unusual PPD-LPAD association in ZRS mutations/duplications has not been specifically reviewed in the literature. The author reviews this unusual entity and gives insights regarding its pathogenesis. PMID:29651423

75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA...) (SEC Approves Consolidated FINRA Rules Governing Financial Responsibility). FINRA announced in...

76 FR 32133 - FAR Council's Plan for Retrospective Review Under Executive Order 13563-Preliminary Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

... (E.O.) 13563, ``Improving Regulation and Regulatory Review.'' The E.O. sets forth principles and... resources and regulatory priorities, under which the agency will periodically review its existing... retrospective analysis. The Council's plan has tentatively identified eight priority initiatives for new or...

How regulatory T cells work

PubMed Central

Vignali, Dario A. A.; Collison, Lauren W.; Workman, Creg J.

2009-01-01

Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting anti-tumour immunity. Given that Treg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we discuss the basic mechanisms used by Treg cells to mediate suppression, and discuss whether one or many of these mechanisms are likely to be crucial for Treg-cell function. In addition, we present the hypothesis that effector T cells may not be ‘innocent’ parties in this suppressive process and might in fact potentiate Treg-cell function. PMID:18566595

Regulatory considerations for pluripotent stem cell therapies.

PubMed

Carpenter, Melissa K

2017-01-01

The development of pluripotent stem cell (PSC) therapies is rapidly advancing, and a number of PSC-derived cell products are currently being tested in clinical trials. The biological complexity of these therapies results in specific challenges in complying with regulatory guidelines. This includes the choice of starting material, reproducible and consistent manufacturing, and preclinical safety and efficacy assessment of the PSC-derived product. This review discusses current US cell therapy regulations and strategies for compliance with these regulations when developing PSC-derived products. © 2017 Elsevier B.V. All rights reserved.

75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

Recent advances in CD8+ regulatory T cell research

PubMed Central

Yu, Yating; Ma, Xinbo; Gong, Rufei; Zhu, Jianmeng; Wei, Lihua; Yao, Jinguang

2018-01-01

Various subgroups of CD8+ T lymphocytes do not only demonstrate cytotoxic effects, but also serve important regulatory roles in the body's immune response. In particular, CD8+ regulatory T cells (CD8+ Tregs), which possess important immunosuppressive functions, are able to effectively block the overreacting immune response and maintain the body's immune homeostasis. In recent years, studies have identified a small set of special CD8+ Tregs that can recognize major histocompatibility complex class Ib molecules, more specifically Qa-1 in mice and HLA-E in humans, and target the self-reactive CD4+ T ce lls. These findings have generated broad implications in the scientific community and attracted general interest to CD8+ Tregs. The present study reviews the recent research progress on CD8+ Tregs, including their origin, functional classification, molecular markers and underlying mechanisms of action.

75 FR 72818 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... Information Management Services, Office of Management invites comments on the submission for OMB review as... Office of Information and Regulatory Affairs, Attention: Education Desk Officer, Office of Management and... Division, Regulatory Information Management Services, Office of Management. Federal Student Aid Type of...

Mapping regulatory models for medicinal cannabis: a matrix of options.

PubMed

Belackova, Vendula; Shanahan, Marian; Ritter, Alison

2017-05-30

Objective The aim of the present study was to develop a framework for assessing regulatory options for medicinal cannabis in Australia. Methods International regulatory regimes for medicinal cannabis were reviewed with a qualitative policy analysis approach and key policy features were synthesised, leading to a conceptual framework that facilitates decision making across multiple dimensions. Results Two central organising dimensions of medicinal cannabis regulation were identified: cannabis supply and patient authorisation (including patient access). A number of the different supply options can be matched with a number of different patient authorisation options, leading to a matrix of possible regulatory regimes. Conclusions The regulatory options, as used internationally, involve different forms of cannabis (synthetic and plant-based pharmaceutical preparations or herbal cannabis) and the varying extent to which patient authorisation policies and procedures are stringently or more loosely defined. The optimal combination of supply and patient authorisation options in any jurisdiction that chooses to make medicinal cannabis accessible will depend on policy goals. What is known about the topic? Internationally, regulation of medicinal cannabis has developed idiosyncratically, depending on formulations that were made available and local context. There has been no attempt to date in the scientific literature to systematically document the variety of regulatory possibilities for medicinal cannabis. What does this paper add? This paper presents a new conceptual schema for considering options for the regulation of medicinal cannabis, across both supply and patient authorisation aspects. What are the implications for practitioners? The design of regulatory systems in Australia, whether for pharmaceutical or herbal products, is a vital issue for policy makers right now as federal and state and territory governments grapple with the complexities of medicinal cannabis

76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

Disrupted regulatory T cell homeostasis in inflammatory bowel diseases

PubMed Central

Pedros, Christophe; Duguet, Fanny; Saoudi, Abdelhadi; Chabod, Marianne

2016-01-01

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20th century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population. PMID:26811641

Disrupted regulatory T cell homeostasis in inflammatory bowel diseases.

PubMed

Pedros, Christophe; Duguet, Fanny; Saoudi, Abdelhadi; Chabod, Marianne

2016-01-21

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.

77 FR 528 - Self-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

...-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting Approval of a Proposed Rule Change To Amend Rules Relating To the Creation of a Service To Provide Post-Trade Information... trading activity of their organizations, their correspondent firms, or both through review of post-trade...

75 FR 5834 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Certain Cross-References and Make Other Various Non-Substantive..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

77 FR 36029 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Rule Cross-References and Make Non- Substantive Technical..., Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers...

76 FR 32246 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Rule Cross-References and Make Non- Substantive Technical..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

Regulatory alerts for dietary supplements in Canada and the United States, 2005-13.

PubMed

Abe, Andrew M; Hein, Darren J; Gregory, Philip J

2015-06-01

Dietary supplement regulatory alerts published by the Food and Drug Administration (FDA) and Health Canada were evaluated and characterized. FDA MedWatch and Health Canada websites were reviewed to identify regulatory alerts regarding dietary supplements from January 1, 2005, through December 31, 2013. Alerts were analyzed to identify product characteristics that may be predictive of product quality issues and potential patient harm. A total of 1560 dietary supplement-related regulatory alerts were identified. Of those, 1287 (83%) were identified through Health Canada, and 273 (18%) were identified through FDA MedWatch. The country of origin of dietary supplements associated with regulatory alerts was not provided in most regulatory alerts; however, when their origin was provided, the United States was the most common. Dietary supplements intended for sexual enhancement were the subject of 33% of all regulatory alerts identified. Products purchased online were the most likely to be associated with a regulatory alert. Dietary supplements intended for sexual enhancement, weight loss, and bodybuilding or athletic performance appeared to pose the greatest risk for patient harm due to product contamination with a pharmaceutical such as a phosphodiesterase-5 inhibitor or sibutramine. Analysis of Canadian and U.S. regulatory alerts concerning dietary supplements revealed that more than 80% of the composite alerts were issued by Health Canada. The most common intended uses of supplements for which alerts were issued were sexual enhancement, weight loss, and bodybuilding or athletic performance. The most common reason for alerts was the presence of a pharmaceutical contaminant. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Functional Association between Regulatory RNAs and the Annexins

PubMed Central

Monastyrskaya, Katia

2018-01-01

Cells respond to pathophysiological states by activation of stress-induced signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed-forward loops which ensure prolongation of the signal, contributing to sustained activation. Members of the annexin protein family act as sensors for Ca2+, pH, and lipid second messengers, and regulate various signalling pathways. Recently, annexins were reported to participate in feedback loops, suppressing miRNA synthesis and attenuating stress-induced dysregulation of gene expression. They can directly or indirectly associate with RNAs, and are transferred between the cells in exosomes and shed microvesicles. The ability of annexins to recruit other proteins and miRNAs into exosomes implicates them in control of cell–cell interactions, affecting the adaptive responses and remodelling processes during disease. The studies summarized in this Review point to an emerging role of annexins in influencing the synthesis, localisation, and transfer of regulatory RNAs. PMID:29462943

77 FR 39313 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...,\\2\\ notice is hereby given that on June 26, 2012, Financial Industry Regulatory Authority, Inc..., as FINRA shall designate, to file such additional financial or operational schedules or reports as...

77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

76 FR 55441 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory... significant aspects of such statements. A. Self-Regulatory Organization's Statement of the Purpose of, and... professional responsibilities, including key regulatory and control themes, as well as the importance of...

Regulatory categories of probiotics across the globe: a review representing existing and recommended categorization.

PubMed

Arora, M; Baldi, A

2015-02-01

Probiotics are friendly live microorganisms (in most cases, bacteria) that are similar to beneficial micro-organisms found in the human gut, whenever consumed, have potential to confer benefit to the health of consumers by maintaining, or improving their intestinal microbial flora and are available to consumers mainly in the form of dietary supplements and foods. All-time high interest in the field of probiotics is due to emerging probiotic industry. Probiotics are available in foods and dietary supplements, even as pharmaceutical formulations (capsules, tablets and powders) and in some other forms as well, but their claims of health benefits may challenge the traditional border between food and medicine. A number of probiotic products have been already introduced into the international market as food supplements, dietary supplements, natural health products, functional foods and many more other categories; as a result, the position of regulatory system for probiotics within existing categories become vague and quite unclear. Common terminology for probiotic products has become a necessity to achieve adequate regulatory control for discussion of probiotic-related issues among government, producers and consumers. The lack of a consistent terminology across the globe leads to legal uncertainty and confusion instead of being a direct obstacle for development of a mature market. This article will explain differences in regulatory categorizations across the globe; discuss the terms like food and drugs with a close relationship to probiotics, the problems associated with unsatisfactorily approached categorization as well as suggestive consolidations for the new categorization which will demarcate probiotics into categories explaining their nutritive claims, health claims or both.

Development of a valid measurement instrument to understand self-regulatory driving practices among older drivers in Malaysia.

PubMed

Yeoh, Sok Foon; Ibrahim, Rahimah; Oxley, Jennifer; Hamid, Tengku Aizan; Rashid, Sharifah Norazizan Syed Abd

2016-07-01

Self-regulatory driving is a term used to describe a strategy used by older drivers to preserve mobility and safety, through the adjustment of driving behaviors to match declining physical functions. It can be regarded as a way to prolong driving, or as a process leading to the cessation of driving. Previous studies have striven to explore and understand how older drivers self-regulate their driving. This paper aims to provide an overview of the relevant theories, to explicate the factors that contribute to the adoption of self-regulated driving and the scales used to measure self-regulatory behaviors. This paper also reports on the development and psychometric testing of a Self-Regulatory Driving Practices (SRDP) scale in the Malaysian context. Based on the reviewed theories, adoption of self-regulatory driving practices is a process and involves cognitive thinking that reflects a set of actions. Existing instruments to measure self-regulatory driving practices have been developed and used to identify the behavioral components of self-regulation. Based on literature reviews and a thematic analysis from focus group discussions, a SRDP scale was developed, accommodating the Malaysian context. There were 498 surveys completed by older drivers for further psychometric testing purposes. Results revealed that the final 12-item SRDP scale (α=0.81) consists of four subscales that are planning, avoidance, reduction and alternatives. Suggestions for future research are also recommended. Copyright © 2016 Elsevier Ltd. All rights reserved.

International regulatory requirements for skin sensitization testing.

PubMed

Daniel, Amber B; Strickland, Judy; Allen, David; Casati, Silvia; Zuang, Valérie; Barroso, João; Whelan, Maurice; Régimbald-Krnel, M J; Kojima, Hajime; Nishikawa, Akiyoshi; Park, Hye-Kyung; Lee, Jong Kwon; Kim, Tae Sung; Delgado, Isabella; Rios, Ludmila; Yang, Ying; Wang, Gangli; Kleinstreuer, Nicole

2018-06-01

Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers. Copyright © 2018 Elsevier Inc. All rights reserved.

Leak-Before-Break: Further developments in regulatory policies and supporting research

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

Wilkowski, G.M.; Chao, K.-S.

1990-02-01

The fourth in a series of international Leak-Before-Break (LBB) Seminars supported in part by the US Nuclear Regulatory Commission was held at the National Central Library in Taipei, Taiwan on May 11 and 12, 1989. The seminar updated the international polices and supporting research on LBB. Attendees included representatives from regulatory agencies, electric utilities, nuclear power plant fabricators, research organizations, and academic institutions. Regulatory policy was the subject of presentations by Mr. G. Arlotto (US NRC, USA) Dr. B. Jarman (AECB, Canada), Dr.P. Milella (ENEA-DISP, Italy), Dr. C. Faidy (EDF/Septen, France ), and Dr. K. Takumi (NUPEC, Japan). A papermore » by Mr. K. Wichman and Mr. A. Lee of the US NRC Office of Nuclear Reactor Regulation is included as background material to these proceedings; it discusses the history and status of LBB applications in US nuclear power plants. In addition, several papers on the supporting research programs described regulatory policy or industry standards for flaw evaluations, e.g., the ASME Section XI code procedures. Supporting research programs were reviewed on the first and second day by several participants from Taiwan, US, Japan, Canada, Italy, and France. Each individual paper has been cataloged separately.« less

International contributions to IAEA-NEA heat transfer databases for supercritical fluids

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

Leung, L. K. H.; Yamada, K.

2012-07-01

An IAEA Coordinated Research Project on 'Heat Transfer Behaviour and Thermohydraulics Code Testing for SCWRs' is being conducted to facilitate collaboration and interaction among participants from 15 organizations. While the project covers several key technology areas relevant to the development of SCWR concepts, it focuses mainly on the heat transfer aspect, which has been identified as the most challenging. Through the collaborating effort, large heat-transfer databases have been compiled for supercritical water and surrogate fluids in tubes, annuli, and bundle subassemblies of various orientations over a wide range of flow conditions. Assessments of several supercritical heat-transfer correlations were performed usingmore » the complied databases. The assessment results are presented. (authors)« less

39 CFR 3060.42 - Commission review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Commission review. 3060.42 Section 3060.42 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL ACCOUNTING PRACTICES AND TAX RULES FOR THE THEORETICAL COMPETITIVE PRODUCTS ENTERPRISE § 3060.42 Commission review. (a) Interested persons shall be provided an...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

75 FR 11605 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-11

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... Reporting Facility and OTC Reporting Facility Fees March 4, 2010. Pursuant to Section 19(b)(1) of the... March 1, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

78 FR 60952 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... hereby given that, on September 24, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed... discussed any comments it received on the proposed rule change. The text of these statements may be examined...

REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS,INFCIRC/540 (Corrected) VOLUME I/III SETTING THE STAGE: 1991-1996.

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

Rosenthal, M.D.; Saum-Manning, L.; Houck, F.

Events in Iraq at the beginning of the 1990s demonstrated that the safeguards system of the International Atomic Energy Agency (IAEA) needed to be improved. It had failed, after all, to detect Iraq's clandestine nuclear weapon program even though some of Iraq's's activities had been pursued at inspected facilities in buildings adjacent to ones being inspected by the IAEA. Although there were aspects of the implementation of safeguards where the IAEA needed to improve, the primary limitations were considered to be part of the safeguards system itself. That system was based on the Nuclear Nonproliferation Treaty of 1970, to whichmore » Iraq was a party, and implemented on the basis of a model NPT safeguards agreement, published by the IAEA 1972 as INFCIRC/153 (corrected). The agreement calls for states to accept and for the IAEA to apply safeguards to all nuclear material in the state. Iraq was a party to such an agreement, but it violated the agreement by concealing nuclear material and other nuclear activities from the IAEA. Although the IAEA was inspecting in Iraq, it was hindered by aspects of the agreement that essentially limited its access to points in declared facilities and provided the IAEA with little information about nuclear activities anywhere else in Iraq. As a result, a major review of the NPT safeguards system was initiated by its Director General and Member States with the objective of finding the best means to enable the IAEA to detect both diversions from declared stocks and any undeclared nuclear material or activities in the state. Significant improvements that could be made within existing legal authority were taken quickly, most importantly a change in 1992 in how and when and what design information would be reported to the IAEA. During 1991-1996, the IAEA pursued intensive study, legal and technical analysis, and field trials and held numerous consultations with Member States. The Board of Governors discussed the issue of strengthening

A review of diazinon use, contamination in surface waters, and regulatory actions in California across water years 1992-2014.

PubMed

Wang, Dan; Singhasemanon, Nan; Goh, Kean S

2017-07-01

Diazinon is an organophosphorus insecticide that has been widely used in the USA and in California resulting in contamination of surface waters. Several federal and state regulations have been implemented with the aim of reducing its impact to human health and the environment, e.g., the cancellation of residential use products by the USEPA and dormant spray regulations by the California Department of Pesticide Regulation. This study reviewed the change in diazinon use and surface water contamination in accordance with the regulatory actions implemented in California over water years 1992-2014. We observed that use amounts began declining when agencies announced the intention to regulate certain use patterns and continued to decline after the implementation of those programs and regulations. The reduction in use amounts led to a downward trend in concentration data and exceedance frequencies in surface waters. Moreover, we concluded that diazinon concentrations in California's surface waters in recent years (i.e., water years 2012-2014) posed a de minimis risk to aquatic organisms.

Regulatory Proteolysis in Arabidopsis-Pathogen Interactions.

PubMed

Pogány, Miklós; Dankó, Tamás; Kámán-Tóth, Evelin; Schwarczinger, Ildikó; Bozsó, Zoltán

2015-09-24

Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is simultaneously used both by plant cells, to recognize and inactivate invading pathogens, and by microbes, to overcome the immune system of the plant and successfully colonize host cells. In this review, we present available results on the group of proteases in the model plant Arabidopsis thaliana whose functions in microbial pathogenesis were confirmed. Pathogen-derived proteolytic factors are also discussed when they are involved in the cleavage of host metabolites. Considering the wealth of review papers available in the field of the ubiquitin-26S proteasome system results on the ubiquitin cascade are not presented. Arabidopsis and its pathogens are conferred with abundant sets of proteases. This review compiles a list of those that are apparently involved in an interaction between the plant and its pathogens, also presenting their molecular partners when available.

Assessment of learning, memory and attention in developmental neurotoxicity regulatory studies: Introduction.

PubMed

Makris, Susan L; Vorhees, Charles V

2015-01-01

There are a variety of chemicals, including pharmaceuticals, that alter neurobehavior following developmental exposure and guidelines for the conduct of studies to detect such effects by statute in the United States and Europe. Guidelines for Developmental Neurotoxicity Testing (DNT) studies issued by the U.S. Environmental Protection Agency (EPA) under prevailing law and European Organization for Economic Cooperation and Development (OECD) recommendations to member countries provide that such studies include a series of neurobehavioral and neuropathological assessments. Among these are assessment of cognitive function, specifically learning and memory. After reviewing 69 DNT studies submitted to the EPA, tests of learning and memory were noted to have detected the lowest observed adverse effect level (LOAELs) less frequently than behavioral tests of locomotor activity and acoustic/auditory startle, but slightly more than for the developmental Functional Observational Battery (devFOB; which is less extensive than the full FOB), but the reasons for the lower LOAEL detection rate for learning and memory assessment could not be determined. A major concern identified in the review, however, was the adequacy of the methods employed in these studies rather than on the importance of learning and memory to the proper assessment of brain function. Accordingly, a symposium was conducted to consider how the guidelines for tests of learning and memory might be improved. Four laboratories with established histories investigating the effects of chemical exposures during development on learning, memory, and attention, were invited to review the topic and offer recommendations, both theoretical and practical, on approaches to improve the assessment of these vital CNS functions. Reviewers were asked to recommend methods that are grounded in functional importance to CNS integrity, well-validated, reliable, and amenable to the context of regulatory studies as well as to basic

Regulatory and ethical considerations for linking clinical and administrative databases.

PubMed

Dokholyan, Rachel S; Muhlbaier, Lawrence H; Falletta, John M; Jacobs, Jeffrey P; Shahian, David; Haan, Constance K; Peterson, Eric D

2009-06-01

Clinical data registries are valuable tools that support evidence development, performance assessment, comparative effectiveness studies, and the adoption of new treatments into routine clinical practice. Although these registries do not have important information on long-term therapies or clinical events, administrative claims databases offer a potentially valuable complement. This article focuses on the regulatory and ethical considerations that arise from the use of registry data for research, including linkage of clinical and administrative data sets. (1) Are such activities primarily designed for quality assessment and improvement, research, or both, as this determines the appropriate ethical and regulatory standards? (2) Does the submission of data to a central registry, which may subsequently be linked to other data sources, require review by the institutional review board (IRB) of each participating organization? (3) What levels and mechanisms of IRB oversight are appropriate for the existence of a linked central data repository and the specific studies that may subsequently be developed using it? (4) Under what circumstances are waivers of informed consent and Health Insurance Portability and Accountability Act authorization required? (5) What are the requirements for a limited data set that would qualify a research activity as not involving human subjects and thus not subject to further IRB review? The approaches outlined in this article represent a local interpretation of the regulations in the context of several clinical data registry projects and focuses on a specific case study of the Society of Thoracic Surgeons National Database.

78 FR 12405 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the... Approval of Change in Ownership, Control, or Business Operations) to provide for a refund of the...

Substantial Equivalence Standards in Tobacco Governance: Statutory Clarity and Regulatory Precedent for the FSPTCA.

PubMed

Carpenter, Daniel; Connolly, Gregory N; Lempert, Lauren Kass

2017-08-01

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 creates the first national system of premarket regulation of tobacco products in American history. The FDA must now review and give marketing authorization to all new tobacco products, based on a public health standard, before they can be legally marketed. Yet the law also contains an alternative pathway for market entry-the substantial equivalence (SE) clause-by which novel and altered tobacco products can be marketed by demonstrating their substantial equivalence to existing products. Over 99 percent of tobacco product applications sent to the FDA under the new law have used this mechanism, and loose application of the SE mechanism carries the risk of undoing the FDA's gatekeeping power under the law. We review the statutory and regulatory precedent for SE, examining the FSPTCA itself as well as regulatory precedent from drug and device regulation (from which the term substantial equivalence and much of the associated statutory language was derived). Our review of standards and scientific precedent demonstrates that exacting scrutiny under the public health standard should govern all SE reviews and that clinical data incorporating social scientific evidence should be routinely required for SE claims by tobacco product sponsors. Copyright © 2017 by Duke University Press.

A primer on thermodynamic-based models for deciphering transcriptional regulatory logic.

PubMed

Dresch, Jacqueline M; Richards, Megan; Ay, Ahmet

2013-09-01

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62476; File No. SR-FINRA-2010-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule Change To Amend FINRA Rule 8312 (FINRA BrokerCheck Disclosure) July 8, 2010. I. Introduction On March 30, 2010, the Financial Industry Regulatory...

PREFACE: 15th Latin American Workshop on Plasma Physics (LAWPP 2014) and 21st IAEA TM on Research Using Small Fusion Devices (RUSFD)

NASA Astrophysics Data System (ADS)

Iván Vargas-Blanco, V.; Herrera-Velázquez, J. Julio E.

2015-03-01

Written contributions from participants of the Joint 15th Latin American Workshop on Plasma Physics (LAWPP 2014) - 21st IAEA Technical Meeting on Research Using Small Fusion Devices (21st IAEA TM RUSFD). The International Advisory Committees of the 15th Latin American Workshop on Plasma Physics (LAWPP 2014) and the 21st IAEA TM on Research Using Small Fusion Devices (RUSFD), agreed to carry out together this Joint LAWPP 2014 - 21st RUSFD in San José, Costa Rica, on 27-31 January 2014. The Joint LAWPP 2014 - 21st RUSFD meeting, organized by the Instituto Tecnológico de Costa Rica, Universidad Nacional de Costa Rica, and Ad Astra Rocket Company in collaboration with the International Atomic Energy Agency (IAEA). The Latin American Workshop on Plasma Physics (LAWPP) is a series of events which has been held periodically since 1982, with the purpose of providing a forum in which the research of the Latin American plasma physics community can be displayed, as well as fostering collaborations among plasma scientists within the region and with researchers from the rest of the world. Recognized plasma scientists from developed countries are specially invited to the meeting to present the state of the art on several "hot" topics related to plasma physics. It is an open meeting, with an International Advisory Committee, in which the working language is English. It was firstly held in 1982 in Cambuquira, Brazil, followed by workshops in Medellín, Colombia (1985), Santiago de Chile, Chile (1988), Buenos Aires, Argentina (1990), Mexico City, Mexico (1992), Foz do Iguaçu, Brazil (1994, combined with the International Congress on Plasma Physics (ICPP)), Caracas, Venezuela (1997), Tandil, Argentina (1998), La Serena, Chile (2000), Sao Pedro, Brazil (2003), Mexico City, Mexico (2005), Caracas, Venezuela (2007), Santiago de Chile, Chile (2010, combined with the ICPP) and Mar de Plata, Argentina (2011). The 21st IAEA TM on Research Using Small Fusion Devices is an ideal forum for

Continuing education requirements among State Occupational Therapy Regulatory Boards in the United States of America.

PubMed

Hall, Savannah R; Crifasi, Kristen A; Marinelli, Christina M; Yuen, Hon K

2016-01-01

The purpose of this study is to compare and contrast the contents of each state's occupational therapy (OT) regulatory board requirements regarding licensees' acquisition of continuing education units in the United States of America. Data related to continuing education requirements from each OT regulatory board of all 50 states and the District of Columbia in the United States were reviewed and categorized by two reviewers. Analysis was conducted based on the categorization of the continuing education requirements and activities required, allowed, and not allowed/not mentioned for continuing education units. Findings revealed non-uniformity and inconsistency of continuing education requirements for licensure renewal between OT regulatory boards and was coupled with lack of specific criteria for various continuing education activities. Continuing education requirements were not tailored to meet the needs of individual licensee's current and anticipated professional role and job responsibilities, with a negative bias towards presentation and publication allowed for continuing education units. Few boards mandated continuing education topics on ethics related to OT practice within each renewal cycle. OT regulatory boards should move towards unifying the reporting format of continuing education requirements across all states to reduce ambiguity and to ensure licensees are equipped to provide ethical and competent practice. Efforts could be made to enact continuing education requirements specific to the primary role of a particular licensee. Finally, assigning the amount of continuing education credits to be awarded for different activities should be based on research evidence rather than arbitrary determination.

Regulatory Approaches for Adding Capacity to Existing Hydropower Facilities

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

Levine, Aaron L.; Curtis, Taylor L.; Kazerooni, Borna

In 2015, hydroelectric generation accounted for more than 6 percent of total net electricity generation in the United States and 46 percent of electricity generation from all renewables. The United States has considerable hydroelectric potential beyond what is already being developed. Nearly 7 GW of this potential is found by adding capacity to existing hydropower facilities. To optimize the value of hydroelectric generation, the U.S. Department of Energy's Hydropower Vision Study highlights the importance of adding capacity to existing facilities. This report provides strategic approaches and considerations for Federal Energy Regulatory Commission licensed and exempt hydropower facilities seeking to increasemore » generation capacity, which may include increases from efficiency upgrades. The regulatory approaches reviewed for this report include capacity and non-capacity amendments, adding capacity during relicensing, and adding capacity when converting a license to a 10-MW exemption.« less

A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers.

PubMed

Henry, Barbara J; Carlin, Joseph P; Hammerschmidt, Jon A; Buck, Robert C; Buxton, L William; Fiedler, Heidelore; Seed, Jennifer; Hernandez, Oscar

2018-05-01

Per- and polyfluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative, and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100 000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on polytetrafluoroethylene (PTFE): acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity and no reproductive, developmental, or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical, chemical, thermal, and biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "polymers of low concern" (PLC). This review concludes that fluoropolymers are distinctly different from other polymeric and nonpolymeric PFAS and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure-activity relationship assessment is not scientifically appropriate. Integr Environ Assess Manag 2018;14:316-334. © 2018 The Authors

Using FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) to isolate active regulatory DNA

PubMed Central