77 FR 4407 - Modernization of Poultry Slaughter Inspection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

...The Food Safety and Inspection Service (FSIS) is proposing a new inspection system for young chicken and turkey slaughter establishments that would replace the current Streamlined Inspection System (SIS), the New Line Speed Inspection System (NELS), and the New Turkey Inspection System (NTIS). The Agency is also proposing several changes that would affect all establishments that slaughter poultry other than ratites, regardless of the inspection system under which they operate. This proposed rule is a result of the Agency's 2011 regulatory review efforts conducted under Executive Order 13563 on Improving Regulation and Regulatory Review.

A New Regulatory Policy for FTTx-Based Next-Generation Access Networks

NASA Astrophysics Data System (ADS)

Makarovič, Boštjan

2013-07-01

This article critically assesses the latest European Commission policies in relation to next-generation access investment that put focus on regulated prices and relaxing of wholesale access obligations. Pointing at the vital socio-legal and economic arguments, it further challenges the assumptions of the current EU regulatory framework and calls for a more contractual utility-based model of regulation instead of the current system that overly relies on market-driven infrastructure-based competition.

Nitrogen modulation of legume root architecture signaling pathways involves phytohormones and small regulatory molecules.

PubMed

Mohd-Radzman, Nadiatul A; Djordjevic, Michael A; Imin, Nijat

2013-10-01

Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

Distribution System Residuals – Is “Detectable” Still Acceptable for Chloramines?

EPA Science Inventory

Recently, Roberson (2014) noted that one of the distribution system issues currently on the regulatory radar is, “Should disinfectant residual requirements be a specific number as opposed to the current detectable residual?” As our title suggests, we seek to assess what it means...

Regulatory behavior and frontal activity: Considering the role of revised-BIS in relative right frontal asymmetry.

PubMed

Gable, Philip A; Neal, Lauren B; Threadgill, A Hunter

2018-01-01

Essential to human behavior are three core personality systems: approach, avoidance, and a regulatory system governing the two motivational systems. Decades of research has linked approach motivation with greater relative left frontal-cortical asymmetry. Other research has linked avoidance motivation with greater relative right frontal-cortical asymmetry. However, past work linking withdrawal motivation with greater relative right frontal asymmetry has been mixed. The current article reviews evidence suggesting that activation of the regulatory system (revised Behavioral Inhibition System [r-BIS]) may be more strongly related to greater relative right frontal asymmetry than withdrawal motivation. Specifically, research suggests that greater activation of the r-BIS is associated with greater relative right frontal activity, and reduced r-BIS activation is associated with reduced right frontal activity (greater relative left frontal activity). We review evidence examining trait and state frontal activity using EEG, source localization, lesion studies, neuronal stimulation, and fMRI supporting the idea that r-BIS may be the core personality system related to greater relative right frontal activity. In addition, the current review seeks to disentangle avoidance motivation and r-BIS as substrates of relative right frontal asymmetry. © 2017 Society for Psychophysiological Research.

[Regulatory Program for Medical Devices in Cuba: experiences and current challenges].

PubMed

Pereira, Dulce María Martínez; Rodríguez, Yadira Álvarez; Valdés, Yamila Cedeño; Ribas, Silvia Delgado

2016-05-01

Regulatory control of medical devices in Cuba is conducted through a system based on the Regulatory Program for Medical Devices as a way to ensure the safety, efficacy, and effectiveness of these technologies, which are in use by the National Health System. This program was launched in 1992, when the Regulations for State Evaluation and Registration of Medical Devices were approved. Its successive stages and the merging of regulatory activities for drugs and medical equipment have meant progress toward stronger, more transparent strategies and greater control of industry and the National Health System. Throughout its course the Cuban program has met with challenges and difficulties that it has addressed by drawing on its own experiences. During the new period, the greatest challenges revolve around ensuring that regulatory systems incorporate scientific evaluation, risk levels, maximum rigor through the use of technical standards, and the implementation of international recommendations, together with the application of the ISO 13485 certification scheme, enhanced market monitoring, and classification of medical devices in accordance with their relevance to the country's national health policies. From the regional standpoint, the greatest challenge lies in working toward regulatory convergence. The Collaborating Centre for the Regulation of Health Technologies will support the proposed regulatory strategy and established regional priorities, in particular in connection with the implementation of actions involving medical devices.

Analysis of the performance of the CONTOUR® TS Blood Glucose Monitoring System: when regulatory performance criteria are met, should we have confidence to use a medical device with all patients?

PubMed

Lyon, Martha E; Lyon, Andrew W

2011-01-01

The article entitled, Performance of the CONTOUR® TS Blood Glucose Monitoring System, by Frank and colleagues in this issue of Journal of Diabetes Science and Technology, demonstrates that the CONTOUR® TS glucose meter exceeds current regulatory expectations for glucose meter performance. However, the appropriateness of current regulatory expectations, such as International Organization for Standardization (ISO) 15197:2003, is being reevaluated because of increasing concern regarding the reliability of glucose meters in ambulatory and hospitalized environments. Between 2004 and 2008, 12,673 serious adverse events with glucose meters that met the ISO 15197 expectations were reported in the Food and Drug Administration-Manufacturer and User Facility Device Experience surveillance database. Should different glucose meter performance criteria be applied to ambulatory versus critical care patients? © 2010 Diabetes Technology Society.

78 FR 51664 - Vessel Traffic Service Updates, Including Establishment of Vessel Traffic Service Requirements...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... requirements. The changes made by this rule will align regulations with the current operating procedures of the... History V. Discussion of Comments and Changes VI. Regulatory Analyses A. Regulatory Planning and Review B... Waterways Safety System PWSA Ports and Waterways Safety Act SOLAS International Convention for the Safety of...

Determinants of Effective Information Transfer in International Regulatory Standards Adoption

ERIC Educational Resources Information Center

Popescu, Denisa

2010-01-01

The role of international regulatory standards within the current global environment has become of the most importance. The age of the global system and free market capitalism carried us into the unprecedented age of regulations, and standard setting. Regulations are now becoming the emerging mode of global governance. This study focuses on…

So Many Chemicals, So Little Time... Evolution of ...

EPA Pesticide Factsheets

Current testing is limited by traditional testing models and regulatory systems. An overview is given of high throughput screening approaches to provide broader chemical and biological coverage, toxicokinetics and molecular pathway data and tools to facilitate utilization for regulatory application. Presentation at the NCSU Toxicology lecture series on the Evolution of Computational Toxicology

76 FR 70190 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

... concern about dark pools and their potential impact on the fairness and transparency of the national market system.\\12\\ One of these commenters suggested that dark pools be prohibited entirely.\\13\\ FINRA... transparency that currently exists.\\14\\ FINRA stated that all trades executed on an ATS, including a dark pool...

Unmanned Aerial Vehicle Systems for Disaster Relief: Tornado Alley

NASA Technical Reports Server (NTRS)

DeBusk, Wesley M.

2009-01-01

Unmanned aerial vehicle systems are currently in limited use for public service missions worldwide. Development of civil unmanned technology in the United States currently lags behind military unmanned technology development in part because of unresolved regulatory and technological issues. Civil unmanned aerial vehicle systems have potential to augment disaster relief and emergency response efforts. Optimal design of aerial systems for such applications will lead to unmanned vehicles which provide maximum potentiality for relief and emergency response while accounting for public safety concerns and regulatory requirements. A case study is presented that demonstrates application of a civil unmanned system to a disaster relief mission with the intent on saving lives. The concept utilizes unmanned aircraft to obtain advanced warning and damage assessments for tornados and severe thunderstorms. Overview of a tornado watch mission architecture as well as commentary on risk, cost, need for, and design tradeoffs for unmanned aerial systems are provided.

Establishment of Application Guidance for OTC non-Kampo Crude Drug Extract Products in Japan

PubMed Central

Somekawa, Layla; Maegawa, Hikoichiro; Tsukada, Shinsuke; Nakamura, Takatoshi

2017-01-01

Currently, there are no standardized regulatory systems for herbal medicinal products worldwide. Communication and sharing of knowledge between different regulatory systems will lead to mutual understanding and might help identify topics which deserve further discussion in the establishment of common standards. Regulatory information on traditional herbal medicinal products in Japan is updated by the establishment of Application Guidance for over-the-counter non-Kampo Crude Drug Extract Products. We would like to report on updated regulatory information on the new Application Guidance. Methods for comparison of Crude Drug Extract formulation and standard decoction and criteria for application and the key points to consider for each criterion are indicated in the guidance. Establishment of the guidance contributes to improvements in public health. We hope that the regulatory information about traditional herbal medicinal products in Japan will be of contribution to tackling the challenging task of regulating traditional herbal products worldwide. PMID:28894633

Polychlorinated Biphenyls (PCBs) in Transit System Electrical Equipment

DOT National Transportation Integrated Search

1984-05-01

This report presents the legislative history and current regulatory requirement concerning the continued use of Polychlorinated Biphenyls (PCBs) in transit system electrical equipment. Recent rule-making promulgated by the Environmental Protection Ag...

Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria.

PubMed

Ibarra-Arellano, Miguel A; Campos-González, Adrián I; Treviño-Quintanilla, Luis G; Tauch, Andreas; Freyre-González, Julio A

2016-01-01

The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy ( A: cross- BA: cteria SY: stems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing 3708 regulons and 1776 systems. All this brings together a large corpus of data that will surely inspire studies to generate hypothesis regarding the principles governing the evolution and organization of systems and the functional architectures controlling them.Database URL: http://abasy.ccg.unam.mx. © The Author(s) 2016. Published by Oxford University Press.

Novel GM animal technologies and their governance.

PubMed

Bruce, Ann; Castle, David; Gibbs, Corrina; Tait, Joyce; Whitelaw, C Bruce A

2013-08-01

Scientific advances in methods of producing genetically modified (GM) animals continue, yet few such animals have reached commercial production. Existing regulations designed for early techniques of genetic modification pose formidable barriers to commercial applications. Radically improved techniques for producing GM animals invite a re-examination of current regulatory regimes. We critically examine current GM animal regulations, with a particular focus on the European Union, through a framework that recognises the importance of interactions among regulatory regimes, innovation outcomes and industry sectors. The current focus on the regulation of risk is necessary but is unable to discriminate among applications and tends to close down broad areas of application rather than facilitate innovation and positive industry interactions. Furthermore, the fields of innovative animal biosciences appear to lack networks of organisations with co-ordinated future oriented actions. Such networks could drive coherent programmes of innovation towards particular visions and contribute actively to the development of regulatory systems for GM animals. The analysis presented makes the case for regulatory consideration of each animal bioscience related innovation on the basis of the nature of the product itself and not the process by which it was developed.

Administration and Regulation of a Military Retirement System Funded by Private Sector Investments

DTIC Science & Technology

1990-03-01

private sector , as opposed to the current method of investing the funds within the Government, between 1985 and 1989, under assumptions of administrative and regulatory constraints; the timeframe was selected because in 1985 the Government began setting aside funds for future military retirement costs versus the pay-as-you-go method in previous years. The study had three objectives: (1) identify administrative factors that result from modifying the current MRS to an MRS funded by private sector investments; (2) identify regulatory constraints that

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

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

Chang 'Apollo', Chen

2006-07-01

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

78 FR 13132 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68960; File No. SR-Phlx-2013-09] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing of Proposed Rule Change To Enhance the Functionality Offered on Its Options Floor Broker Management System (``FBMS'') by, Among Other Things, Automating Functions Currently Performed by Floor...

The UAV and the Current and Future Regulatory Construction for Integration into the National Airspace System

DTIC Science & Technology

2005-07-01

vehicles to deliver mail or packages across town, in a large indoor complex or building, or even to deliver...drugs, marihuana , depressants or stimulants.330 Further, current licenses and certified personnel may have their

Analysis of Regulatory Guidance for Health Monitoring

NASA Technical Reports Server (NTRS)

Munns, Thomas E.; Beard, Richard E.; Culp, Aubrey M.; Murphy, Dennis A.; Kent, Renee M.; Cooper, Eric G. (Technical Monitor)

2000-01-01

The purpose of this study was to assess the connection between current FAA regulations and the incorporation of Health Management (HM) systems into commercial aircraft. To address the overall objectives ARINC: (1) investigated FAA regulatory guidance, (2) investigated airline maintenance practices, (3) systematically identified regulations and practices that would be affected or could act as barriers to the introduction of HM technology, and (4) assessed regulatory and operational tradeoffs that should be considered for implementation. The assessment procedure was validated on a postulated structural HM capability for the B757 horizontal stabilizer.

Biobanking and Privacy Law in Brazil.

PubMed

Dallari, Sueli Gandolfi; Castellaro, Felipe Angel Bocchi; Guerriero, Iara Coelho Zito

2015-01-01

This article analyzes the current regulatory framework for biobanking, genomic research, and protection of privacy in Brazil. It is divided in four parts. The first describes the biobanking context in Brazil and its evolution in recent years. In the second, the entire regulatory framework on biobanking and genomic research is analyzed. The third part focuses on the critical evaluation of this regulatory framework, specifically on some major ethical dilemmas in biobanking. The fourth part describes the characteristics of the Brazilian biobanking and human research governance system, known as the CEP/CONEP system. Finally, the conclusion summarizes the information in the article and its contribution to the study of the biobanking ethical challenges, especially the protection of privacy. It is highlighted that biobanking regulatory harmonization among countries is necessary, since it increases scientific possibilities that can come from broader cooperation among biobanks and several research centers on the national and international levels. © 2015 American Society of Law, Medicine & Ethics, Inc.

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.

Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies.

PubMed

Strickland, Judy; Clippinger, Amy J; Brown, Jeffrey; Allen, David; Jacobs, Abigail; Matheson, Joanna; Lowit, Anna; Reinke, Emily N; Johnson, Mark S; Quinn, Michael J; Mattie, David; Fitzpatrick, Suzanne C; Ahir, Surender; Kleinstreuer, Nicole; Casey, Warren

2018-04-01

Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information must first be clarified. Thus, we reviewed acute systemic toxicity testing requirements for six U.S. agencies (Consumer Product Safety Commission, Department of Defense, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, Occupational Safety and Health Administration) and noted whether there is flexibility in satisfying data needs with methods that replace or reduce animal use. Understanding the current regulatory use and acceptance of non-animal data is a necessary starting point for future method development, optimization, and validation efforts. The current review will inform the development of a national strategy and roadmap for implementing non-animal approaches to assess potential hazards associated with acute exposures to industrial chemicals and medical products. The Acute Toxicity Workgroup of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), U.S. agencies, non-governmental organizations, and other stakeholders will work to execute this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

Health sector regulation in Thailand: recent progress and the future agenda.

PubMed

Teerawattananon, Yot; Tangcharoensathien, Viroj; Tantivess, Sripen; Mills, Anne

2003-03-01

This paper reviews the current system of regulation and assesses its effectiveness in the health-care system of Thailand. In order to achieve this, extensive documentary reviews were performed and supplemented by in-depth interviews. We found the existing regulatory framework to be fairly comprehensive with rules and roles firmly established. Regulations cover almost all relevant private and public organisations including individuals. However, the incomplete performance of regulatory functions was detected resulting in problems of overburdened staff and delays in performance of functions. Our recommendations propose the promotion of professional ethics and continuing education, an effort to narrow the gap between expectation and reality through public education, and the empowering of consumer organisations. The increasing popularity of medical lawsuits and professional insurance, which in part reflects the imperfect administration of the system, highlights the need for careful consideration of how best to handle the increase in complaints. The mapping of the regulatory system in this paper, together with the discussion of how to cope with the expansion of medicine as a business and with greater consumerism, will be of interest to other middle income countries that seek to reform and strengthen their regulatory system.

HANDBOOK: CONTINUOUS EMISSION MONITORING SYSTEMS FOR NON-CRITERIA POLLUTANTS

EPA Science Inventory

This Handbook provides a description of the methods used to continuously monitor non-criteria pollutants emitted from stationary sources. The Handbook contains a review of current regulatory programs, the state-of-the-art sampling system design, analytical techniques, and the use...

Improving medical device regulation: the United States and Europe in perspective.

PubMed

Sorenson, Corinna; Drummond, Michael

2014-03-01

Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States and Europe to ensure their performance, safety, and quality. This article provides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients. We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peer-reviewed literature and legislative documents. The two regulatory systems differ in their mandate and orientation, organization, pre- and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring real-world use, and exchanging pertinent information on devices with key users such as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered. Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring high-quality evidence of benefit for medium- and high-risk devices; moving toward greater centralization and coordination of regulatory approval in Europe; creating links between device identifier systems and existing data collection tools, such as electronic health records; and fostering increased and more effective use of registries to ensure safe postmarket use of new and existing devices. © 2014 Milbank Memorial Fund.

Improving Medical Device Regulation: The United States and Europe in Perspective

PubMed Central

SORENSON, CORINNA; DRUMMOND, MICHAEL

2014-01-01

Context: Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States and Europe to ensure their performance, safety, and quality. This article provides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients. Methods: We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peer-reviewed literature and legislative documents. Findings: The two regulatory systems differ in their mandate and orientation, organization, pre-and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring real-world use, and exchanging pertinent information on devices with key users such as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered. Conclusions: Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring high-quality evidence of benefit for medium-and high-risk devices; moving toward greater centralization and coordination of regulatory approval in Europe; creating links between device identifier systems and existing data collection tools, such as electronic health records; and fostering increased and more effective use of registries to ensure safe postmarket use of new and existing devices. PMID:24597558

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

PubMed

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

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

Regulating the unknown: Managing the occupational health risks of nanomedical technologies and nanopharmaceuticals in the research laboratory

NASA Astrophysics Data System (ADS)

Ersin, Ozlem Hacer

Novel technologies and their resultant products demand fresh ways of thinking about pre-market risk analysis and post-market surveillance. A regulatory framework that is responsive to emerging knowledge about the hazards of novel technologies offers repeatable and transparent processes and remains economically and socially feasible. Workers are an especially vulnerable population who are exposed to unknown hazards of novel technologies and serve often as unwitting sentinels of impending risks. This Grounded Theory-based case study identifies gaps in our current ability to regulate novel technologies so as to minimize occupational health risks and offers necessary modifications for an environment that is conducive to proper regulation. Nanopharmaceuticals and the nano-based technologies at their base are used by way of exemplar technologies that are currently taxing the ability of the regulatory system to provide adequate oversight. Ambiguities of definition, absence of a tracking system (of who is doing nanotechnology research), and the paucity of scientific evidence to support risk management efforts are among the findings of the study and need to be addressed as ameliorative steps toward an effective regulatory structure.

TRICARE revision to CHAMPUS DRG-based payment system, pricing of hospital claims. Final rule.

PubMed

2014-05-21

This Final rule changes TRICARE's current regulatory provision for inpatient hospital claims priced under the DRG-based payment system. Claims are currently priced by using the rates and weights that are in effect on a beneficiary's date of admission. This Final rule changes that provision to price such claims by using the rates and weights that are in effect on a beneficiary's date of discharge.

Current limitations and recommendations to improve testing ...

EPA Pesticide Factsheets

In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizations, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or the environment. Current test systems include in silico, in vitro and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormonal pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1)adequately sensitive species and life-stages, 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern, and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive in regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to, and guidance for existing test methods, and to reduce uncertainty. For example, in vitro high throughput

21 CFR 26.10 - Regulatory authorities not listed as currently equivalent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE...

KINETICS OF THM AND HAA PRODUCTION IN A SIMULATED DISTRIBUTION SYSTEM

EPA Science Inventory

Limited data exist on how the growth of halogenated disinfection by-products (DBPs) is affected by time spent in a distribution system. such information is needed to estimate human exposures to these chemicals for both regulatory analyses and epidemiological studies. Current me...

[Convergence of healthcare regulation in the Americas: history, development, and new challenges].

PubMed

Silva, Ana Paula Jucá; Tagliari, Patrícia Oliveira Pereira

2016-05-01

The present article describes the changing relationship among healthcare regulatory authorities in various international settings, with special emphasis on the Americas. As other sectors, healthcare also faces the need to regulate international practices, while at the same time taking into consideration the specific realities of each country. Regulatory convergence - a movement towards technical alignment to enable the adoption of local regulatory mechanisms that take into account internationally recognized standards and principles to promote a single sanitary goal - has emerged as a means to address this challenge. Organizations that already use this tool, such as the International Conference of Drug Regulatory Authorities (ICDRA), Pan American Network for Drug Regulatory Harmonization (PANDRH), International Generic Drug Regulators Programme (IGDRP), and the International Medical Device Regulators Forum (IMDRF), among others, are currently working to gather knowledge, data, and specialists from different countries to build an international technical and scientific standard that can be used for decision-making by local regulators. This would ensure convergence of national regulations despite the need to adapt international standards to local needs, structure, and capacities. The most recent resolutions issued by the World Health Organization recognize the need to bring regulatory systems closer to the reality of national healthcare systems, and underscore the advantages of using existing local guidelines as input for cooperation with regulatory authorities.

Networking Omic Data to Envisage Systems Biological Regulation.

PubMed

Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae

To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.

The role of regulatory B cells in digestive system diseases.

PubMed

Zhou, Zhenyu; Gong, Lei; Wang, Xiaoyun; Hu, Zhen; Wu, Gaojue; Tang, Xuejun; Peng, Xiaobin; Tang, Shuan; Meng, Miao; Feng, Hui

2017-04-01

The past decade has provided striking insights into a newly identified subset of B cells known as regulatory B cells (Bregs). In addition to producing antibody, Bregs also regulate diseases via cytokine production and antigen presentation. This subset of B cells has protective and potentially therapeutic effects. However, the particularity of Bregs has caused some difficulties in conducting research on their roles. Notably, human B10 cells, which are Bregs that produce interleukin 10, share phenotypic characteristics with other previously defined B cell subsets, and currently, there is no known surface phenotype that is unique to B10 cells. An online search was performed in the PubMed and Web of Science databases for articles published providing evidences on the role of regulatory B cells in digestive system diseases. Abundant evidence has demonstrated that Bregs play a regulatory role in inflammatory, autoimmune, and tumor diseases, and regulatory B cells play different roles in different diseases, but future work needs to determine the mechanisms by which Bregs are activated and how these cells affect their target cells.

Influence of commercial laying hen housing systems on the incidence and identification of Salmonella and Campylobacter

USDA-ARS?s Scientific Manuscript database

The housing of laying hens is important for social, industrial, and regulatory aspects. Many studies have compared hen housing systems on the research farm, but few have fully examined commercial housing systems and management strategies. The current study compared hens housed in commercial cage-f...

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Regulatory aspects in the pharmaceutical development of nanoparticle drug delivery systems designed to cross the intestinal epithelium and M-cells.

PubMed

Hussain, Nasir

2016-11-30

This article reviews the field of oral uptake of nanoparticles across the gastrointestinal epithelium for the period 2006-2016. Analysis is conducted from the viewpoint of i) M-cell genetics and model development, ii) drug targeting to Peyer's patches and M-cells, and iii) physicochemical interactions of nanoparticles in the intestinal milieu. In light of these recent developments, regulatory considerations in the development of orally-absorbable nanoparticle drug products are discussed and focused on Module 3.2.P sub-sections of the Common Technical Document. Particular attention is paid to novel excipients, ligands and the non-standard method of manufacture. The novelty of this drug delivery system demands not only a multi-disciplinary scientific and regulatory approach but also a risk-adjusted consideration for a system defined by both processes and specifications. Given the current state of scientific development in the field it is suggested (in the author's personal opinion) that the design of nanoparticulate drug delivery systems should be kept as simple as possible (from a regulatory and manufacturing perspective) and to target the entire gastrointestinal epithelium. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Underground storage tank management plan, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

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

NONE

1997-09-01

The Underground Storage Tank (UST) Program at the Oak Ridge Y-12 Plant was established to locate UST systems at the facility and to ensure that all operating UST systems are free of leaks. UST systems have been removed or upgraded in accordance with Tennessee Department of Environment and Conservation (TDEC) regulations and guidance. With the closure of a significant portion of the USTs, the continuing mission of the UST Management Program is to manage the remaining active UST systems and continue corrective actions in a safe regulatory compliant manner. This Program outlines the compliance issues that must be addressed, reviewsmore » the current UST inventory and compliance approach, and presents the status and planned activities associated with each UST system. The UST Program provides guidance for implementing TDEC regulations and guidelines for petroleum UST systems. The plan is divided into three major sections: (1) regulatory requirements, (2) active UST sites, and (3) out-of-service UST sites. These sections describe in detail the applicable regulatory drivers, the UST sites addressed under the Program, and the procedures and guidance for compliance.« less

Hours of work and rest in the rail industry.

PubMed

Anderson, C; Grunstein, R R; Rajaratnam, S M W

2013-06-01

Currently, the National Transport Commission is considering four options to form the regulatory framework for rail safety within Australia with respect to fatigue. While the National Transport Commission currently recommends no limitations around hours of work or rest, we provide evidence which suggests regulatory frameworks should incorporate a traditional hours of service regulation over more flexible policies. Our review highlights: Shift durations >12 h are associated with a doubling of risk for accident and injury. Fatigue builds cumulatively with each successive shift where rest in between is inadequate (<12 h). A regulatory framework for fatigue management within the rail industry should prescribe limits on hours of work and rest, including maximum shift duration and successive number of shifts. Appropriately, validated biomathematical models and technologies may be used as a part of a fatigue management system, to augment the protection afforded by limits on hours of work and rest. A comprehensive sleep disorder screening and management programme should form an essential component of any regulatory framework. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Current State of the Regulatory Trajectory for Whole Slide Imaging Devices in the USA

PubMed Central

Abels, Esther; Pantanowitz, Liron

2017-01-01

The regulatory field for digital pathology (DP) has advanced significantly. A major milestone was accomplished when the FDA allowed the first vendor to market their device for primary diagnostic use in the USA and published in the classification order that this device, and substantially equivalent devices of this generic type, should be classified into class II instead of class III as previously proposed. The Digital Pathology Association (DPA) regulatory task force had a major role in the accomplishment of getting the application request for Whole Slide Imaging (WSI) Systems recommended for a de novo. This article reviews the past and emerging regulatory environment of WSI for clinical use in the USA. A WSI system with integrated subsystems is defined in the context of medical device regulations. The FDA technical performance assessment guideline is also discussed as well as parameters involved in analytical testing and clinical studies to demonstrate that WSI devices are safe and effective for clinical use. PMID:28584684

Current State of the Regulatory Trajectory for Whole Slide Imaging Devices in the USA.

PubMed

Abels, Esther; Pantanowitz, Liron

2017-01-01

The regulatory field for digital pathology (DP) has advanced significantly. A major milestone was accomplished when the FDA allowed the first vendor to market their device for primary diagnostic use in the USA and published in the classification order that this device, and substantially equivalent devices of this generic type, should be classified into class II instead of class III as previously proposed. The Digital Pathology Association (DPA) regulatory task force had a major role in the accomplishment of getting the application request for Whole Slide Imaging (WSI) Systems recommended for a de novo . This article reviews the past and emerging regulatory environment of WSI for clinical use in the USA. A WSI system with integrated subsystems is defined in the context of medical device regulations. The FDA technical performance assessment guideline is also discussed as well as parameters involved in analytical testing and clinical studies to demonstrate that WSI devices are safe and effective for clinical use.

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

PubMed

Gordon, Sarah; Daneshian, Mardas; Bouwstra, Joke; Caloni, Francesca; Constant, Samuel; Davies, Donna E; Dandekar, Gudrun; Guzman, Carlos A; Fabian, Eric; Haltner, Eleonore; Hartung, Thomas; Hasiwa, Nina; Hayden, Patrick; Kandarova, Helena; Khare, Sangeeta; Krug, Harald F; Kneuer, Carsten; Leist, Marcel; Lian, Guoping; Marx, Uwe; Metzger, Marco; Ott, Katharina; Prieto, Pilar; Roberts, Michael S; Roggen, Erwin L; Tralau, Tewes; van den Braak, Claudia; Walles, Heike; Lehr, Claus-Michael

2015-01-01

Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

A systems approach for management of pests and pathogens of nursery crops

Treesearch

Jennifer L. Parke; Niklaus J. Grünwald

2012-01-01

Horticultural nurseries are heterogeneous and spatially complex agricultural systems, which present formidable challenges to management of diseases and pests. Moreover, nursery plants shipped interstate and internationally can serve as important vectors for pathogens and pests that threaten both agriculture and forestry. Current regulatory strategies to prevent this...

Microbiological impact of three commercial laying hen housing systems

USDA-ARS?s Scientific Manuscript database

Hen housing for commercial egg production continues to be a societal and regulatory concern. Controlled studies have examined various aspects of egg safety but a comprehensive assessment of commercial hen housing systems in the US has not been conducted. The current study is part of a holistic, mu...

76 FR 25389 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing of Proposed Rule...

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The Occurrence of Contaminant Accumulation in Lead Pipe Scales from Domestic Drinking Water Distribution Systems-ABSTRACT

EPA Science Inventory

Previous work has shown that contaminants such as Al, As and Ra, can accumulate in drinking water distribution system solids. The release of accumulated contaminants back into the water supply could conceivably result in elevated levels at consumers’ taps. The current regulatory...

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78 FR 4949 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Instituting Proceedings To...

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2013-01-23

... system) and orders utilizing the INAV Pegged Order functionality for that ETF already in the system would... on a flawed INAV (e.g., whether such orders would be cancellable). The commenter questions the... represents that it currently utilizes a number of systems and processes aimed at detecting dissemination or...

End of FY10 report - used fuel disposition technical bases and lessons learned : legal and regulatory framework for high-level waste disposition in the United States.

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

Weiner, Ruth F.; Blink, James A.; Rechard, Robert Paul

This report examines the current policy, legal, and regulatory framework pertaining to used nuclear fuel and high level waste management in the United States. The goal is to identify potential changes that if made could add flexibility and possibly improve the chances of successfully implementing technical aspects of a nuclear waste policy. Experience suggests that the regulatory framework should be established prior to initiating future repository development. Concerning specifics of the regulatory framework, reasonable expectation as the standard of proof was successfully implemented and could be retained in the future; yet, the current classification system for radioactive waste, including hazardousmore » constituents, warrants reexamination. Whether or not consideration of multiple sites are considered simultaneously in the future, inclusion of mechanisms such as deliberate use of performance assessment to manage site characterization would be wise. Because of experience gained here and abroad, diversity of geologic media is not particularly necessary as a criterion in site selection guidelines for multiple sites. Stepwise development of the repository program that includes flexibility also warrants serious consideration. Furthermore, integration of the waste management system from storage, transportation, and disposition, should be examined and would be facilitated by integration of the legal and regulatory framework. Finally, in order to enhance acceptability of future repository development, the national policy should be cognizant of those policy and technical attributes that enhance initial acceptance, and those policy and technical attributes that maintain and broaden credibility.« less

Mammalian synthetic biology for studying the cell

PubMed Central

Mathur, Melina; Xiang, Joy S.

2017-01-01

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. PMID:27932576

Gene Regulation, Two Component Regulatory Systems, and Adaptive Responses in Treponema Denticola.

PubMed

Marconi, Richard T

2017-10-13

The oral microbiome consists of a remarkably diverse group of 500-700 bacterial species. The microbial etiology of periodontal disease is similarly complex. Of the ~400 bacterial species identified in subgingival plaque, at least 50 belong to the genus Treponema. As periodontal disease develops and progresses, T. denticola transitions from a low to high abundance species in the subgingival crevice. Changes in the overall composition of the bacterial population trigger significant changes in the local physical, immunological and physiochemical conditions. For T. denticola to thrive in periodontal pockets, it must be nimble and adapt to rapidly changing environmental conditions. The purpose of this chapter is to review the current understanding of the molecular basis of these essential adaptive responses, with a focus on the role of two component regulatory systems with global regulatory potential.

77 FR 27505 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

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... trading centers. With respect to the price of the routed limit order, Rule 11.15(a)(ii)(A) currently provides: ``Each such converted limit order shall be priced at the price of the protected quotation that it...)(ii)(A), the Exchange's trading system, NSX BLADE[supreg] (``Blade''), currently prices each such...

Evaluation of training programs and entry-level qualifications for nuclear-power-plant control-room personnel based on the systems approach to training

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

Haas, P M; Selby, D L; Hanley, M J

1983-09-01

This report summarizes results of research sponsored by the US Nuclear Regulatory Commission (NRC) Office of Nuclear Regulatory Research to initiate the use of the Systems Approach to Training in the evaluation of training programs and entry level qualifications for nuclear power plant (NPP) personnel. Variables (performance shaping factors) of potential importance to personnel selection and training are identified, and research to more rigorously define an operationally useful taxonomy of those variables is recommended. A high-level model of the Systems Approach to Training for use in the nuclear industry, which could serve as a model for NRC evaluation of industrymore » programs, is presented. The model is consistent with current publically stated NRC policy, with the approach being followed by the Institute for Nuclear Power Operations, and with current training technology. Checklists to be used by NRC evaluators to assess training programs for NPP control-room personnel are proposed which are based on this model.« less

Recombinant drug development, regulation, and commercialization: an Indian industry perspective.

PubMed

Sahoo, Niharika; Manchikanti, Padmavati

2011-04-01

The Indian biopharmaceutical sector comprises nearly 40 companies that manufacture and/or market 14 recombinant drugs that account for nearly 50 products. Among these, 22 companies have manufacturing facilities in India. The aim of the present study was to analyze the patenting trends, commercialization, and regulatory system for biopharmaceuticals in India. Representatives from 19 such biopharmaceutical companies were interviewed on aspects related to regulatory compliance, manufacturing, commercialization, and innovation in order to understand the challenges faced by them in the current regulatory and patent system. The study revealed that 94% of the companies have filed patents and 52% are developing new biologic entities in areas such as diabetes mellitus, cancer, and congestive heart diseases. Forty-two percent of the companies consider delays in regulatory approval to be a major constraint for biopharmaceutical industry development. Almost all are of the opinion that uniform guidelines across countries would help to prevent delays in the commercialization of products. A high proportion of representatives of the biopharmaceutical industry in India identified that elaboration of regulatory guidelines, defined submission requirements, and drug approval timelines are vital to the growth of the biopharmaceutical industry. © 2011 Adis Data Information BV. All rights reserved.

A Qualitative Assessment of Current CCF Guidance Based on a Review of Safety System Digital Implementation Changes with Evolving Technology

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

Korsah, Kofi; Muhlheim, Michael David; Wood, Richard

The US Nuclear Regulatory Commission (NRC) is initiating a new rulemaking project to develop a digital system common-cause failure (CCF) rule. This rulemaking will review and modify or affirm the NRC's current digital system CCF policy as discussed in the Staff Requirements Memorandum to the Secretary of the Commission, Office of the NRC (SECY) 93-087, Policy, Technical, and Licensing Issues Pertaining to Evolutionary and Advanced Light Water Reactor (ALWR) Designs, and Branch Technical Position (BTP) 7-19, Guidance on Evaluation of Defense-in-Depth and Diversity in Digital Computer-Based Instrumentation and Control Systems, as well as Chapter 7, Instrumentation and Controls, in NRCmore » Regulatory Guide (NUREG)-0800, Standard Review Plan for Review of Safety Analysis Reports for Nuclear Power Plants (ML033580677). The Oak Ridge National Laboratory (ORNL) is providing technical support to the NRC staff on the CCF rulemaking, and this report is one of several providing the technical basis to inform NRC staff members. For the task described in this report, ORNL examined instrumentation and controls (I&C) technology implementations in nuclear power plants in the light of current CCF guidance. The intent was to assess whether the current position on CCF is adequate given the evolutions in digital safety system implementations and, if gaps in the guidance were found, to provide recommendations as to how these gaps could be closed.« less

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.

The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

PubMed Central

Jahan-Mihan, Alireza; Rodriguez, Judith; Christie, Catherine; Sadeghi, Marjan; Zerbe, Tara

2015-01-01

The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring. PMID:26561832

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... current National Best Bid and National Best Offer, or if no National Best Bid or National Best Offer, at... the System to the Designated Percentage away from the then current National Best Bid and National Best Offer, or, if no National Best Bid or National Best Offer, to the Designated Percentage away from the...

Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy.

PubMed

Klimczak, Dominika; Jazdzewski, Krystian; Kuch, Marek

2017-02-01

Multiple factors underlie the pathophysiology of hypertension, involving endothelial dysregulation, vascular smooth muscle dysfunction, increased oxidative stress, sympathetic nervous system activation and altered renin -angiotensin -aldosterone regulatory activity. A class of non-coding RNA called microRNA, consisting of 17-25 nucleotides, exert regulatory function over these processes. This paper summarizes the currently available data from preclinical and clinical studies on miRNA in the development of hypertension as well as the impact of anti-hypertensive treatment on their plasma expression. We present microRNAs' characteristics, their biogenesis and role in the regulation of blood pressure together with their potential diagnostic and therapeutic application in clinical practice.

Mammalian synthetic biology for studying the cell.

PubMed

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Investment, regulation, and uncertainty: managing new plant breeding techniques.

PubMed

Smyth, Stuart J; McDonald, Jillian; Falck-Zepeda, Jose

2014-01-01

As with any technological innovation, time refines the technology, improving upon the original version of the innovative product. The initial GM crops had single traits for either herbicide tolerance or insect resistance. Current varieties have both of these traits stacked together and in many cases other abiotic and biotic traits have also been stacked. This innovation requires investment. While this is relatively straight forward, certain conditions need to exist such that investments can be facilitated. The principle requirement for investment is that regulatory frameworks render consistent and timely decisions. If the certainty of regulatory outcomes weakens, the potential for changes in investment patterns increases.   This article provides a summary background to the leading plant breeding technologies that are either currently being used to develop new crop varieties or are in the pipeline to be applied to plant breeding within the next few years. Challenges for existing regulatory systems are highlighted. Utilizing an option value approach from investment literature, an assessment of uncertainty regarding the regulatory approval for these varying techniques is undertaken. This research highlights which technology development options have the greatest degree of uncertainty and hence, which ones might be expected to see an investment decline.

Investment, regulation, and uncertainty

PubMed Central

Smyth, Stuart J; McDonald, Jillian; Falck-Zepeda, Jose

2014-01-01

As with any technological innovation, time refines the technology, improving upon the original version of the innovative product. The initial GM crops had single traits for either herbicide tolerance or insect resistance. Current varieties have both of these traits stacked together and in many cases other abiotic and biotic traits have also been stacked. This innovation requires investment. While this is relatively straight forward, certain conditions need to exist such that investments can be facilitated. The principle requirement for investment is that regulatory frameworks render consistent and timely decisions. If the certainty of regulatory outcomes weakens, the potential for changes in investment patterns increases.   This article provides a summary background to the leading plant breeding technologies that are either currently being used to develop new crop varieties or are in the pipeline to be applied to plant breeding within the next few years. Challenges for existing regulatory systems are highlighted. Utilizing an option value approach from investment literature, an assessment of uncertainty regarding the regulatory approval for these varying techniques is undertaken. This research highlights which technology development options have the greatest degree of uncertainty and hence, which ones might be expected to see an investment decline. PMID:24499745

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.

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 processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots.

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 processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots. PMID:22563474

Animal use in the chemical and product manufacturing sectors - can the downtrend continue?

PubMed

Curren, Rodger

2009-12-01

During the 1990s and early 2000s, a number of manufacturing companies in the cosmetic, personal care and household product industries were able to substantially reduce their use of animals for testing (or to not use animals in the first place). These reductions were almost always the result of significant financial contributions to either direct, in-house alternatives research, or to support personnel whose duties were to understand and apply the current state-of-the-art for in vitro testing. They occurred almost exclusively in non-regulatory areas, and primarily involved acute topical toxicities. Over the last few years, the reduction in animal use has been much less dramatic, because some companies are still reluctant to change from the traditional animal studies, because systemic, repeat-dose toxicity is more difficult to model in vitro, and because many products still require animal testing for regulatory approval. Encouragingly, we are now observing an increased acceptance of non-animal methods by regulatory agencies. This is due to mounting scientific evidence from larger databases, agreement by companies to share data and testing strategies with regulatory agencies, and a focus on smaller domains of applicability. These changes, along with new emphasis and financial support for addressing systemic toxicities, promise to provide additional possibilities for industry to replace animals with in vitro methods, alone or in combination with in silico methods. However, the largest advance will not occur until more companies commit to using the non-animal test strategies that are currently available. 2009 FRAME.

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.

75 FR 68657 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-08

... LLC To Increase the Maximum Order Size Accepted by Floor Broker Systems From 25,000,000 Shares to 99... order size accepted by Floor broker systems from 25,000,000 shares to 99,000,000 shares. The text of the... systems shall accept a maximum order size of 99,000,000, an increase from the current 25,000,000 share...

Interaction initiatives between regulatory, health technology assessment and coverage bodies, and industry.

PubMed

Frønsdal, Katrine; Pichler, Franz; Mardhani-Bayne, Logan; Henshall, Chris; Røttingen, John-Arne; Mørland, Berit; Klemp, Marianne

2012-10-01

There has been an increased focus on the relationship between health technology assessment (HTA) and regulatory assessments and how regulatory, HTA and coverage bodies, and industry can work better together to improve efficiency and alignment of processes. There is increasingly agreement across sectors that improved communication and coordination could contribute to facilitating timely patient access to effective, affordable treatments that offer value to the health system. Discussions on aspects of this relationship are being held in different forums and various forms of coordination and collaboration are being developed or piloted within several jurisdictions. It is therefore both timely and of value to stakeholders to describe and reflect on current initiatives intended to improve interactions between regulatory, HTA and coverage bodies, and industry. Drawing on 2011 meetings of the HTAi Policy Forum and the Center for Innovation in Regulatory Science (CIRS), this study aims to describe and compare initiatives, and point to success factors and challenges that are likely to inform future work and collaboration.

78 FR 48513 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing of Proposed Rule Change To Adopt...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... reduce the systemic and administrative burdens on market participants by avoiding the need for... enforce NYSE Arca rules, as the NYSE would do under its current rule. In sum, the Exchange believes that...

Evolving PBPK applications in regulatory risk assessment: current situation and future goals

EPA Science Inventory

The presentation includes current applications of PBPK modeling in regulatory risk assessment and discussions on conflicts between assuring consistency with experimental data in current situation and the desire for animal-free model development.

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 from a GE evaluation process that currently focuses only on risk assessment and identifying ever diminishing marginal hazards, to a regulatory approach that more objectively evaluates and communicates the likely impact of approving a new GE plant or animal on agricultural production systems.

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 from a GE evaluation process that currently focuses only on risk assessment and identifying ever diminishing marginal hazards, to a regulatory approach that more objectively evaluates and communicates the likely impact of approving a new GE plant or animal on agricultural production systems. PMID:24066781

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

PubMed

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

2015-11-01

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

Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

PubMed

Mittra, J; Tait, J; Mastroeni, M; Turner, M L; Mountford, J C; Bruce, K

2015-01-25

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Response to Nuclear Regulatory Commission`s ten questions pertaining to site-specific models for use in the license termination rule: Multimedia Environmental Pollutant Assessment System (MEPAS)

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

Buck, J.W.; Whelan, G.; Strenge, D.L.

This paper is in response to the US Nuclear Regulatory Commission (NRC) ten questions posed at the Modeling Workshop held November 13 and 14, 1997. The ten questions were developed in advance of the workshop to allow model developers to prepare a presentation at the Workshop. This paper is an expanded version of the Multimedia Environmental Pollutant Assessment System (MEPAS) presentation given at the Modeling Workshop by Pacific Northwest National Laboratory (PNNL) staff. This paper is organized by the ten questions asked by the NRC, each section devoted to a single question. The current version of methodology is MEPAS 3.2more » (NRC 1997) and the discussion in this paper will pertain to that version. In some cases, MEPAS 4.0, which is currently being developed under the Framework for Risk Analysis in Multimedia Environmental Systems (FRAMES) (Whelan et al. 1997), will be referenced to inform the reader of potential capabilities in the near future. A separate paper is included in the document that discusses the FRAMES concept.« less

Development of a rational scale to assess the harm of drugs of potential misuse.

PubMed

Nutt, David; King, Leslie A; Saulsbury, William; Blakemore, Colin

2007-03-24

Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

Regulatory challenges and approaches to characterize nanomedicines and their follow-on similars.

PubMed

Mühlebach, Stefan; Borchard, Gerrit; Yildiz, Selcan

2015-03-01

Nanomedicines are highly complex products and are the result of difficult to control manufacturing processes. Nonbiological complex drugs and their biological counterparts can comprise nanoparticles and therefore show nanomedicine characteristics. They consist of not fully known nonhomomolecular structures, and can therefore not be characterized by physicochemical means only. Also, intended copies of nanomedicines (follow-on similars) may have clinically meaningful differences, creating the regulatory challenge of how to grant a high degree of assurance for patients' benefit and safety. As an example, the current regulatory approach for marketing authorization of intended copies of nonbiological complex drugs appears inappropriate; also, a valid strategy incorporating the complexity of such systems is undefined. To demonstrate sufficient similarity and comparability, a stepwise quality, nonclinical and clinical approach is necessary to obtain market authorization for follow-on products as therapeutic alternatives, substitution and/or interchangeable products. To fill the regulatory gap, harmonized and science-based standards are needed.

Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development.

PubMed

Sverdlov, Oleksandr; van Dam, Joris; Hannesdottir, Kristin; Thornton-Wells, Tricia

2018-07-01

Digital therapeutics represent a new treatment modality in which digital systems such as smartphone apps are used as regulatory-approved, prescribed therapeutic interventions to treat medical conditions. In this article we provide a critical overview of the rationale for investing in such novel modalities, including the unmet medical needs addressed by digital therapeutics and the potential for reducing current costs of medical care. We also discuss emerging pathways to regulatory approval and how innovative business models are enabling further growth in the development of digital therapeutics. We conclude by providing some recent examples of digital therapeutics that have gained regulatory approval and highlight opportunities for the near future. © 2018 American Society for Clinical Pharmacology and Therapeutics.

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

PathCase-SB architecture and database design

PubMed Central

2011-01-01

Background Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. Description PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database. Conclusions PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world. PMID:22070889

USEPA BIOMONITORING AND BIOINDICATORS CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring ...

US EPA BIOMONITORING AND BIOINDICATOR CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring ...

USEPA BIOMONITORING AND BIOINDICATOR CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring...

So Many Chemicals, So Little Time... Evolution of Computational Toxicology (NCSU Toxicology Lecture Series)

EPA Science Inventory

Current testing is limited by traditional testing models and regulatory systems. An overview is given of high throughput screening approaches to provide broader chemical and biological coverage, toxicokinetics and molecular pathway data and tools to facilitate utilization for reg...

Unmanned aircraft systems in wildlife research: Current and future applications of a transformative technology

USGS Publications Warehouse

Christie, Katherine S.; Gilbert, Sophie L.; Brown, Casey L.; Hatfield, Michael; Hanson, Leanne

2016-01-01

Unmanned aircraft systems (UAS) – also called unmanned aerial vehicles (UAVs) or drones – are an emerging tool that may provide a safer, more cost-effective, and quieter alternative to traditional research methods. We review examples where UAS have been used to document wildlife abundance, behavior, and habitat, and illustrate the strengths and weaknesses of this technology with two case studies. We summarize research on behavioral responses of wildlife to UAS, and discuss the need to understand how recreational and commercial applications of this technology could disturb certain species. Currently, the widespread implementation of UAS by scientists is limited by flight range, regulatory frameworks, and a lack of validation. UAS are most effective when used to examine smaller areas close to their launch sites, whereas manned aircraft are recommended for surveying greater distances. The growing demand for UAS in research and industry is driving rapid regulatory and technological progress, which in turn will make them more accessible and effective as analytical tools.

Dissecting innate immune responses with the tools of systems biology.

PubMed

Smith, Kelly D; Bolouri, Hamid

2005-02-01

Systems biology strives to derive accurate predictive descriptions of complex systems such as innate immunity. The innate immune system is essential for host defense, yet the resulting inflammatory response must be tightly regulated. Current understanding indicates that this system is controlled by complex regulatory networks, which maintain homoeostasis while accurately distinguishing pathogenic infections from harmless exposures. Recent studies have used high throughput technologies and computational techniques that presage predictive models and will be the foundation of a systems level understanding of innate immunity.

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.

Systems identification and the adaptive management of waterfowl in the United States

USGS Publications Warehouse

Williams, B.K.; Nichols, J.D.

2001-01-01

Waterfowl management in the United States is one of the more visible conservation success stories in the United States. It is authorized and supported by appropriate legislative authorities, based on large-scale monitoring programs, and widely accepted by the public. The process is one of only a limited number of large-scale examples of effective collaboration between research and management, integrating scientific information with management in a coherent framework for regulatory decision-making. However, harvest management continues to face some serious technical problems, many of which focus on sequential identification of the resource system in a context of optimal decision-making. The objective of this paper is to provide a theoretical foundation of adaptive harvest management, the approach currently in use in the United States for regulatory decision-making. We lay out the legal and institutional framework for adaptive harvest management and provide a formal description of regulatory decision-making in terms of adaptive optimization. We discuss some technical and institutional challenges in applying adaptive harvest management and focus specifically on methods of estimating resource states for linear resource systems.

Validation of the digital opacity compliance system under regulatory enforcement conditions.

PubMed

McFarland, Michael J; Rasmussen, Steve L; Stone, Daniel A; Palmer, Glenn R; Wander, Joseph D

2006-09-01

U.S. Environmental Protection Agency (EPA) Emission Measurement Center in conjunction with EPA Regions VI and VIII, the state of Utah, and the U.S. Department of Defense have conducted a series of long-term pilot and field tests to determine the accuracy and reliability of a visible opacity monitoring system consisting of a conventional digital camera and a separate computer software application for plume opacity determination. This technology, known as the Digital Opacity Compliance System (DOCS), has been successfully demonstrated at EPA-sponsored Method-9 "smoke schools", as well as at a number of government and commercially operated industrial facilities. Results from the current DOCS regulatory pilot study demonstrated that, under regulatory enforcement conditions, the average difference in opacity measurement between the DOCS technology and EPA Reference Method 9 (Method 9) was 1.12%. This opacity difference, which was computed from the evaluation of 241 regulated air sources, was found to be statistically significant at the 99% confidence level. In evaluating only those sources for which a nonzero visible opacity level was recorded, the

[Better medical devices regulations for better health care: enlightenment for medical devices regulatory reform in China, from experiences of the E.U. and the U.S.A].

PubMed

Sun, Qin; Yan, Liang

2006-01-01

The expansion of applications of medical devices has attracted the increased attention of government regulatory bodies around the world to the safety and effectiveness of these products. Most developed countries, such as the United States and European Union, have developed well-established regulatory systems for medical devices, which have also consistently been amended to accommodate the changing requirements of safety and the trend of globalization.The current "Regulations for the Supervision and Administration of Medical Device (China)", established in 2000, has brought about great improvements for the safety and effectiveness of products, safeguarding public health. But there are still, at present, a lot of counterfeit and poor quality devices and device-related adverse events for lack of powerful post -market and in-use regulatory controls for products. It is therefore very urgent for the Chinese government to reform its medical device administration and management. This research paper analyses and compares the different requirements and executions of medical devices regulations in the EU, the US and China, to draw some experiences of the EU and US regimes that are very useful to China's regulatory reform. It is suggested that when developing a new scheme of medical devices regulatory reform in China, two prominent aspects have to be considered by policy makers and regulators. Firstly, the global trend of medical devices regulations has to be taken into account. Secondly, the experiences learned from the EU and US systems should be applied to the Chinese regulatory reform in combination with the concrete practice of China.

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

USGS Publications Warehouse

Coady, Katherine K.; Biever, Ronald C.; Denslow, Nancy D.; Gross, Melanie; Guiney, Patrick D.; Holbech, Henrik; Karouna-Renier, Natalie K.; Katsiadaki, Ioanna; Krueger, Hank; Levine, Steven L.; Maack, Gerd; Williams, Mike; Wolf, Jeffrey C.; Ankley, Gerald T.

2017-01-01

In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. 

ON FARM SAMPLING FOR SALMONELLA: IMPACT OF METHOD AND DESIGN ON RESULTS

USDA-ARS?s Scientific Manuscript database

Current sampling for the National Antimicrobial Resistance Monitoring System (NARMS) is comprised primarily of receipt of Salmonella isolates from the USDA FSIS as part of their regulatory compliance testing. These isolates are received from all commodities and product classes. Isolates are charac...

75 FR 34970 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... Regulatory Affairs, Office of Management and Budget (OMB), [email protected] or fax (202) 395-5806... information unless it displays a currently valid OMB control number. Food and Nutrition Service Title...: The Food and Nutrition Service (FNS) has developed Education and Administrative reporting System (EARS...

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.

BOA: Asbestos pipe-insulation removal robot system, Phase 2. Topical report, January--June 1995

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

Schempf, H.; Bares, J.E.

This report explored the regulatory impact and cost-benefit of a robotic thermal asbestos pipe-insulation removal system over the current manual abatement work practice. The authors are currently in the second phase of a two-phase program to develop a robotic asbestos abatement system, comprised of a ground-based support system (including vacuum, fluid delivery, computing/electronics/power, and other subsystems) and several on-pipe removal units, each sized to handle pipes within a given diameter range. The intent of this study was to (i) aid in developing design and operational criteria for the overall system to maximize cost-efficiency, and (ii) to determine the commercial potentialmore » of a robotic pipe-insulation abatement system.« less

Dynamic RSA: Examining parasympathetic regulatory dynamics via vector-autoregressive modeling of time-varying RSA and heart period.

PubMed

Fisher, Aaron J; Reeves, Jonathan W; Chi, Cyrus

2016-07-01

Expanding on recently published methods, the current study presents an approach to estimating the dynamic, regulatory effect of the parasympathetic nervous system on heart period on a moment-to-moment basis. We estimated second-to-second variation in respiratory sinus arrhythmia (RSA) in order to estimate the contemporaneous and time-lagged relationships among RSA, interbeat interval (IBI), and respiration rate via vector autoregression. Moreover, we modeled these relationships at lags of 1 s to 10 s, in order to evaluate the optimal latency for estimating dynamic RSA effects. The IBI (t) on RSA (t-n) regression parameter was extracted from individual models as an operationalization of the regulatory effect of RSA on IBI-referred to as dynamic RSA (dRSA). Dynamic RSA positively correlated with standard averages of heart rate and negatively correlated with standard averages of RSA. We propose that dRSA reflects the active downregulation of heart period by the parasympathetic nervous system and thus represents a novel metric that provides incremental validity in the measurement of autonomic cardiac control-specifically, a method by which parasympathetic regulatory effects can be measured in process. © 2016 Society for Psychophysiological Research.

Application of SAE ARP4754A to Flight Critical Systems

NASA Technical Reports Server (NTRS)

Peterson, Eric M.

2015-01-01

This report documents applications of ARP4754A to the development of modern computer-based (i.e., digital electronics, software and network-based) aircraft systems. This study is to offer insight and provide educational value relative to the guidelines in ARP4754A and provide an assessment of the current state-of-the- practice within industry and regulatory bodies relative to development assurance for complex and safety-critical computer-based aircraft systems.

Micro-CT imaging: Developing criteria for examining fetal skeletons in regulatory developmental toxicology studies - A workshop report.

PubMed

Solomon, Howard M; Makris, Susan L; Alsaid, Hasan; Bermudez, Oscar; Beyer, Bruce K; Chen, Antong; Chen, Connie L; Chen, Zhou; Chmielewski, Gary; DeLise, Anthony M; de Schaepdrijver, Luc; Dogdas, Belma; French, Julian; Harrouk, Wafa; Helfgott, Jonathan; Henkelman, R Mark; Hesterman, Jacob; Hew, Kok-Wah; Hoberman, Alan; Lo, Cecilia W; McDougal, Andrew; Minck, Daniel R; Scott, Lelia; Stewart, Jane; Sutherland, Vicki; Tatiparthi, Arun K; Winkelmann, Christopher T; Wise, L David; Wood, Sandra L; Ying, Xiaoyou

2016-06-01

During the past two decades the use and refinements of imaging modalities have markedly increased making it possible to image embryos and fetuses used in pivotal nonclinical studies submitted to regulatory agencies. Implementing these technologies into the Good Laboratory Practice environment requires rigorous testing, validation, and documentation to ensure the reproducibility of data. A workshop on current practices and regulatory requirements was held with the goal of defining minimal criteria for the proper implementation of these technologies and subsequent submission to regulatory agencies. Micro-computed tomography (micro-CT) is especially well suited for high-throughput evaluations, and is gaining popularity to evaluate fetal skeletons to assess the potential developmental toxicity of test agents. This workshop was convened to help scientists in the developmental toxicology field understand and apply micro-CT technology to nonclinical toxicology studies and facilitate the regulatory acceptance of imaging data. Presentations and workshop discussions covered: (1) principles of micro-CT fetal imaging; (2) concordance of findings with conventional skeletal evaluations; and (3) regulatory requirements for validating the system. Establishing these requirements for micro-CT examination can provide a path forward for laboratories considering implementing this technology and provide regulatory agencies with a basis to consider the acceptability of data generated via this technology. Published by Elsevier Inc.

75 FR 68656 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-08

... Shares to 99,000,000 Shares November 2, 2010. Pursuant to Section 19(b)(1) \\1\\ of the Securities Exchange... size accepted by Floor broker systems from 25,000,000 shares to 99,000,000 shares. The text of the... systems shall accept a maximum order size of 99,000,000, an increase from the current 25,000,000 share...

Gaps, inexperience, inconsistencies, and overlaps: crisis in the regulation of genetically modified plants and animals.

PubMed

Mandal, Gregory N

2004-04-01

The regulation of genetically modified products pursuant to statutes enacted decades prior to the advent of biotechnology has created a regulatory system that is passive rather than proactive about risks, has difficulty adapting to biotechnology advances, and is highly fractured and inefficient--transgenic plants and animals are governed by at least twelve different statutes and five different agencies or services. The deficiencies resulting from this piecemeal approach to regulation unnecessarily expose society and the environment to adverse risks of biotechnology and introduce numerous inefficiencies into the regulatory system. These risks and inefficiencies include gaps in regulation, duplicative and inconsistent regulation, unnecessary increases in the cost of and delay in the development and commercialization of new biotechnology products. These deficiencies also increase the risk of further unnecessary biotechnology scares, which may cause public overreaction against biotechnology products, preventing the maximization of social welfare. With science and society poised to soar from first-generation biotechnology (focused on crops modified for agricultural benefit), to next-generation developments (including transgenic fish, insects, and livestock, and pharmaceutical-producing and industrial compound-producing plants and animals), it is necessary to establish a comprehensive, efficient, and scientifically rigorous regulatory system. This Article details how to achieve such a result through fixing the deficiencies in, and risks created by, the current regulatory structure. Ignoring many details, the solutions can be summarized in two categories. First, statutory and regulatory gaps that are identified must be closed with new legislation and regulation. Second, regulation of genetically modified products must be shifted from a haphazard model based on statutes not intended to cover biotechnology to a system based upon agency expertise in handling particular types of risks.

77 FR 62270 - Proposed Revision Treatment of Non-Safety Systems for Passive Advanced Light Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... for Passive Advanced Light Water Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Standard... Passive Advanced Light Water Reactors.'' The current SRP does not contain guidance on the proposed RTNSS for Passive Advance Light Water Reactors. DATES: Submit comments by November 13, 2012. Comments...

International Mutual Recognition: Progress and Prospects. Working Paper.

ERIC Educational Resources Information Center

Hager, Paul

Increasing the mobility of service providers, including professionals, via mutual recognition (of regulatory systems) agreements (MRAs) has become a significant issue worldwide. Despite increasing interest in MRAs, it may be argued that MRAs are but one of a larger range of major developments that have fueled current interest in occupational…

76 FR 42663 - Magnuson-Stevens Fishery Conservation and Management Act Provisions; Fisheries of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

... through daily Vessel Monitoring System (VMS) catch reports, as is currently proposed through a regulatory..., transfer, receive, sell, purchase, trade, or barter; or attempt to transfer, receive, sell, purchase, trade, or barter, or sell more than 2,000 lb (907 kg) of Atlantic [[Page 42670

78 FR 40403 - Energy Conservation Program for Consumer Products and Certain Commercial and Industrial Equipment...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

... from today's proposed determination. There currently is no statutory definition of portable ACs. DOE...\\ Transparency Media Research. Air Conditioning Systems Market--Global Scenario, Trends, Industry Analysis, Size... amended by the Small Business Regulatory Enforcement Fairness Act of 1996) requires preparation of an...

Anaerobic disinfestation induced changes to the soil microbiome, disease incidence and strawberry fruit yields in California field trials

USDA-ARS?s Scientific Manuscript database

Soil-borne disease management in California strawberry production systems has historically relied upon pre-plant soil fumigation. Restricted efficacy of currently available fumigant chemistries towards certain pathogens and regulatory actions limiting treated acreage has stimulated interest in deve...

76 FR 72203 - Voltage Coordination on High Voltage Grids; Notice of Reliability Workshop Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD12-5-000] Voltage... currently coordinate the dispatch of reactive resources to support forecasted loads, generation and... reactive power needs of the distribution system or loads are coordinated or optimized. Panelists: Khaled...

77 FR 13257 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

... Service Title: Emergency Management Response System (EMRS). OMB Control Number: 0579-0071. Summary of... Regulatory Affairs, Office of Management and Budget (OMB), [email protected] or fax (202) 395-5806... displays a currently valid OMB control number and the agency informs potential persons who are to respond...

78 FR 78071 - Protection of Stratospheric Ozone: Adjustments to the Allowance System for Controlling HCFC...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... an individual consumption baseline year to each company by selecting its highest ODP-weighted... 2003-2009 regulatory period, using each company's highest ``production year'' or ``consumption year... 605 based on an EPA determination regarding current scientific information or the availability of...

An Assessment of the ECTS in Software Engineering: A Teaching Experience

ERIC Educational Resources Information Center

Salas-Morera, L.; Berral-Yeron, J.; Serrano-Gomez, I.; Martinez-Jimenez, P.

2009-01-01

Spain is currently implementing the regulatory modifications promulgated by the Declaration of Bologna, which should result in the updating of the structure of university degrees, and the inclusion of the European Credit Transfer and Accumulation System (ECTS) methodology. In some Spanish universities, the experimental adoption of this methodology…

75 FR 36147 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

..., as Modified by Amendment No. 1 Thereto, Related to the Hybrid Matching Algorithms June 17, 2010. On... Hybrid System. Each rule currently provides allocation algorithms the Exchange can utilize when executing incoming electronic orders, including the Ultimate Matching Algorithm (``UMA''), and price-time and pro...

Towards the Next Generation Air Quality Modeling System: Current Progress on Implementing Chemistry into MPAS-A

EPA Science Inventory

The community multiscale air quality (CMAQ) model of the U.S. Environmental Protection Agency is one of the most widely used air quality model worldwide; it is employed for both research and regulatory applications at major universities and government agencies for improving under...

Introduction: MicroRNAs in human reproduction: small molecules with crucial regulatory roles.

PubMed

Imbar, Tal; Galliano, Daniela; Pellicer, Antonio; Laufer, Neri

2014-06-01

MicroRNAs constitute a large family of approximately 21-nucleotide-long, noncoding RNAs. They emerged more than 20 years ago as key posttranscriptional regulators of gene expression. The regulatory role of these small RNA molecules has recently begun to be explored in the human reproductive system. In this issue's Views and Reviews, the authors present the current knowledge regarding the involvement of microRNAs in several aspects of human reproduction and discuss its future implications for clinical practice. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

European union regulatory developments for new vaccine adjuvants and delivery systems.

PubMed

Sesardic, Dorothea; Dobbelaer, Roland

2004-06-23

Interest in vaccine adjuvants and new delivery systems has grown rapidly over the past few years. New vaccine candidates have emerged, which, because of their poor immunogenicity, rely on adjuvants to improve their presentation and targeting and to potentiate their protective immune response. Better understandings of the mechanisms of action, together with logistic and economical considerations have resulted in an explosion of technologies. However, there have been few new registered products for human use, and antigens incorporated into immunostimulating reconstituted influenza virosomes have only relatively recently been licensed in European Union (EU) countries. Influenza vaccine, adjuvanted with water in oil emulsion containing squalene (adjuvant MF59C1) is now also approved. Although current EU regulations focus on traditional adjuvants, notably aluminium and calcium salts, advances have been made in regulatory considerations. The European agency for the evaluation of medicinal products, through its working parties, is actively drafting guidance on requirements for the evaluation of new adjuvants in vaccines. This paper summarises the new developments in EU regulatory aspects relevant to adjuvant quality at development stages, during the manufacturing process, and at the final bulk stage of adjuvant with antigen, and also summarises regulatory expectation regarding safety at pre-clinical and clinical stages. The paper highlights the regulatory concerns and existing bottlenecks that have led to slow approval of new technologies.

A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

PubMed Central

2011-01-01

Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis. PMID:21232107

75 FR 45685 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... list (see current List 7 titled Misrepresentation/Omissions, List 9 titled Negligence/Breach of... claims alleging misrepresentation/ omissions (see current List 8, Item 1), negligence/breach of fiduciary... claims alleging misrepresentation/ omission (see current List 8, Item 2), negligence/breach of fiduciary...

A Statistical Testing Approach for Quantifying Software Reliability; Application to an Example System

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

Chu, Tsong-Lun; Varuttamaseni, Athi; Baek, Joo-Seok

The U.S. Nuclear Regulatory Commission (NRC) encourages the use of probabilistic risk assessment (PRA) technology in all regulatory matters, to the extent supported by the state-of-the-art in PRA methods and data. Although much has been accomplished in the area of risk-informed regulation, risk assessment for digital systems has not been fully developed. The NRC established a plan for research on digital systems to identify and develop methods, analytical tools, and regulatory guidance for (1) including models of digital systems in the PRAs of nuclear power plants (NPPs), and (2) incorporating digital systems in the NRC's risk-informed licensing and oversight activities.more » Under NRC's sponsorship, Brookhaven National Laboratory (BNL) explored approaches for addressing the failures of digital instrumentation and control (I and C) systems in the current NPP PRA framework. Specific areas investigated included PRA modeling digital hardware, development of a philosophical basis for defining software failure, and identification of desirable attributes of quantitative software reliability methods. Based on the earlier research, statistical testing is considered a promising method for quantifying software reliability. This paper describes a statistical software testing approach for quantifying software reliability and applies it to the loop-operating control system (LOCS) of an experimental loop of the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL).« less

Risk management and regulations for lower limb medical exoskeletons: a review

PubMed Central

He, Yongtian; Eguren, David; Luu, Trieu Phat; Contreras-Vidal, Jose L

2017-01-01

Gait disability is a major health care problem worldwide. Powered exoskeletons have recently emerged as devices that can enable users with gait disabilities to ambulate in an upright posture, and potentially bring other clinical benefits. In 2014, the US Food and Drug Administration approved marketing of the ReWalk™ Personal Exoskeleton as a class II medical device with special controls. Since then, Indego™ and Ekso™ have also received regulatory approval. With similar trends worldwide, this industry is likely to grow rapidly. On the other hand, the regulatory science of powered exoskeletons is still developing. The type and extent of probable risks of these devices are yet to be understood, and industry standards are yet to be developed. To address this gap, Manufacturer and User Facility Device Experience, Clinicaltrials.gov, and PubMed databases were searched for reports of adverse events and inclusion and exclusion criteria involving the use of lower limb powered exoskeletons. Current inclusion and exclusion criteria, which can determine probable risks, were found to be diverse. Reported adverse events and identified risks of current devices are also wide-ranging. In light of these findings, current regulations, standards, and regulatory procedures for medical device applications in the USA, Europe, and Japan were also compared. There is a need to raise awareness of probable risks associated with the use of powered exoskeletons and to develop adequate countermeasures, standards, and regulations for these human-machine systems. With appropriate risk mitigation strategies, adequate standards, comprehensive reporting of adverse events, and regulatory oversight, powered exoskeletons may one day allow individuals with gait disabilities to safely and independently ambulate. PMID:28533700

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

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

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

1997-02-01

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

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.

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Control systems engineering in continuous pharmaceutical manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Small Unmanned Aerial Systems: Implications of the Evolving Legal Context for Use in Natural Resources Science and Management

NASA Astrophysics Data System (ADS)

Walker, M. J.

2016-12-01

Small unmanned aerial systems (sUAS, also known as drones) potentially provide researchers and managers with the capacity to enhance temporal and spatial resolution of data sets for natural resources science and management. sUAS have been used for many types of data collection and have a partial definition in mass of the aircraft, ranging from 0.5 to <55 lbs (0.2 to <24.9 kg). Aircraft within this range of mass can present a collision hazard to other aircraft. The Federal Aviation Administration (FAA) recently faced the challenge of removing regulatory barriers to sUAS application while minimizing risk in the national airspace. The regulatory and legal framework developed for using sUAS in natural resources science and management has evolved from a very conservative approach prior in the first decade of the 21st century. FAA's recently revised operating rules for sUAS, significantly changing pilot certification requirements and operating rules in the national airspace. The next 2-5 years will bring advances in sUAS applications for science and management, building upon the accomplishments of users who complied with the former regulatory environment. We review the current operating rules (49 CFR, part 107) that apply specifically to sUAS and discuss the implications for researchers and managers. While part 107 relaxed many restrictions, it is important to understand the regulatory framework currently in place that encourages development of applications for sUAS while adhering to the mandate that the national airspace be safe and secure. We consider potential applications for natural resources science and management in the context of the recently released operating rules, especially with respect to training requirements and protocols for use.

Protecting sensitive systems and data in an open agency

NASA Technical Reports Server (NTRS)

Hunt, Douglas B.; Tompkins, Frederick G.

1987-01-01

This paper focuses on the policy and definitional issues associated with providing adequate and reasonable levels of protection for sensitive systems and data in an agency whose basic charter mandates the open sharing of information and transfer of technology into the market economy. An information model based on current Federal regulatory issuances is presented. A scheme for determining sensitivity levels, based on a categorization taxonomy,is provided.

Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems

PubMed Central

Anderson, Monique L; Califf, Robert M; Sugarman, Jeremy

2015-01-01

Cluster randomized trials (CRTs) randomly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals. Recent emphasis on quality improvement, comparative effectiveness, and learning health systems has prompted expanded use of pragmatic CRTs in routine healthcare settings, which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address. The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic CRTs but challenges remain, including some arising from the current U.S. research and healthcare regulations. In order to examine the ethical, regulatory, and practical questions facing pragmatic CRTs in healthcare settings, the National Institutes of Health (NIH) Health Care Systems Research Collaboratory convened a workshop in Bethesda, Maryland in July of 2013. Attendees included experts in clinical trials, patient advocacy, research ethics, and research regulations from academia, industry, the NIH, and other federal agencies. Workshop participants identified substantial barriers to implementing these types of CRTs, including issues related to research design, gatekeepers and governance in health systems, consent, institutional review boards, data monitoring, privacy, and special populations. We describe these barriers and suggest means for understanding and overcoming them to facilitate pragmatic CRTs in healthcare settings. PMID:25733677

Virulent and pathogenic features on the Cronobacter sakazakii polymyxin resistant pmr mutant strain s-3.

PubMed

Bao, Xuerui; Yang, Ling; Chen, Lequn; Li, Bing; Li, Lin; Li, Yanyan; Xu, Zhenbo

2017-09-01

Cronobacter sakazakii is a well-known opportunistic pathogen responsible for necrotizing enterocolitis, meningitis and septicaemia in the premature, immunocompromised infants and neonates. This pathogen possesses various virulence factors and regulatory systems, and pmrA/pmrB regulatory system has been identified in a variety of bacterial species. The current study aims to investigate role of pmrA gene in the pathogenicity and virulence characteristics of Cronobacter sakazakii using whole genome sequencing and RNA-seq. Results demonstrated that the absence of pmrA has the potential to affect Cronobacter sakazakii on its pathogenicity, virulence and resistance abilities by regulating expression of numerous related genes, including CusB, CusC, CusR and ESA_pESA3p05434. Copyright © 2017 Elsevier Ltd. All rights reserved.

WhatsApp in Stroke Systems: Current Use and Regulatory Concerns.

PubMed

Calleja-Castillo, Juan M; Gonzalez-Calderon, Gina

2018-01-01

Smartphone use is extremely common. Applications such as WhatsApp have billions of users and physicians are no exception. Stroke Medicine is a field where instant communication among fairly large groups is essential. In developing countries, economic limitations preclude the possibility of acquiring proper communication platforms. Thus, WhatsApp has been used as an organizational tool, for sharing clinical data, and for real time guidance of clinical care decisions. It has evolved into a cheap, accessible tool for telemedicine. Nevertheless, regulatory and privacy issues must be addressed. Some countries have implemented legislation to address this issue, while others lag behind. In this article, we present an overview on the different roles WhatsApp has acquired as a clinical tool in stroke systems and the potential privacy concerns of its use.

WhatsApp in Stroke Systems: Current Use and Regulatory Concerns

PubMed Central

Calleja-Castillo, Juan M.; Gonzalez-Calderon, Gina

2018-01-01

Smartphone use is extremely common. Applications such as WhatsApp have billions of users and physicians are no exception. Stroke Medicine is a field where instant communication among fairly large groups is essential. In developing countries, economic limitations preclude the possibility of acquiring proper communication platforms. Thus, WhatsApp has been used as an organizational tool, for sharing clinical data, and for real time guidance of clinical care decisions. It has evolved into a cheap, accessible tool for telemedicine. Nevertheless, regulatory and privacy issues must be addressed. Some countries have implemented legislation to address this issue, while others lag behind. In this article, we present an overview on the different roles WhatsApp has acquired as a clinical tool in stroke systems and the potential privacy concerns of its use. PMID:29904369

Establishing a Quality Control System for Stem Cell-Based Medicinal Products in China

PubMed Central

2015-01-01

Stem cell-based medicinal products (SCMPs) are emerging as novel therapeutic products. The success of its development depends on the existence of an effective quality control system, which is constituted by quality control technologies, standards, reference materials, guidelines, and the associated management system in accordance with regulatory requirements along product lifespan. However, a worldwide, effective quality control system specific for SCMPs is still far from established partially due to the limited understanding of stem cell sciences and lack of quality control technologies for accurately assessing the safety and biological effectiveness of SCMPs before clinical use. Even though, based on the existing regulations and current stem cell sciences and technologies, initial actions toward the goal of establishing such a system have been taken as exemplified by recent development of new “interim guidelines” for governing quality control along development of SCMPs and new development of the associated quality control technologies in China. In this review, we first briefly introduced the major institutions involved in the regulation of cell substrates and therapeutic cell products in China and the existing regulatory documents and technical guidelines used as critical references for developing the new interim guidelines. With focus only on nonhematopoietic stem cells, we then discussed the principal quality attributes of SCMPs as well as our thinking of proper testing approaches to be established with relevant evaluation technologies to ensure all quality requirements of SCMPs along different manufacturing processes and development stages. At the end, some regulatory and technical challenges were also discussed with the conclusion that combined efforts should be taken to promote stem cell regulatory sciences to establish the effective quality control system for SCMPs. PMID:25471126

Scientific foundation of regulating ionizing radiation: application of metrics for evaluation of regulatory science information.

PubMed

Moghissi, A Alan; Gerraa, Vikrham Kumar; McBride, Dennis K; Swetnam, Michael

2014-11-01

This paper starts by describing the historical evolution of assessment of biologic effects of ionizing radiation leading to the linear non-threshold (LNT) system currently used to regulate exposure to ionizing radiation. The paper describes briefly the concept of Best Available Science (BAS) and Metrics for Evaluation of Scientific Claims (MESC) derived for BAS. It identifies three phases of regulatory science consisting of the initial phase, when the regulators had to develop regulations without having the needed scientific information; the exploratory phase, when relevant tools were developed; and the standard operating phase, when the tools were applied to regulations. Subsequently, an attempt is made to apply the BAS/MESC system to various stages of LNT. This paper then compares the exposure limits imposed by regulatory agencies and also compares them with naturally occurring radiation at several cities. Controversies about LNT are addressed, including judgments of the U.S. National Academies and their French counterpart. The paper concludes that, based on the BAS/MESC system, there is no disagreement between the two academies on the scientific foundation of LNT; instead, the disagreement is based on their judgment or speculation.

Exercise-related hypoglycemia in diabetes mellitus

PubMed Central

Younk, Lisa M; Mikeladze, Maia; Tate, Donna; Davis, Stephen N

2011-01-01

Current recommendations are that people with Type 1 and Type 2 diabetes mellitus exercise regularly. However, in cases in which insulin or insulin secretagogues are used to manage diabetes, patients have an increased risk of developing hypoglycemia, which is amplified during and after exercise. Repeated episodes of hypoglycemia blunt autonomic nervous system, neuroendocrine and metabolic defenses (counter-regulatory responses) against subsequent episodes of falling blood glucose levels during exercise. Likewise, antecedent exercise blunts counter-regulatory responses to subsequent hypoglycemia. This can lead to a vicious cycle, by which each episode of either exercise or hypoglycemia further blunts counter-regulatory responses. Although contemporary insulin therapies cannot fully mimic physiologic changes in insulin secretion, people with diabetes have several management options to avoid hypoglycemia during and after exercise, including regularly monitoring blood glucose, reducing basal and/or bolus insulin, and consuming supplemental carbohydrates. PMID:21339838

Unwelcome Guests: Extoic Forest Pests

Treesearch

Sun Jiang-Hua

2002-01-01

Exotic forest pests cost China and the United States billions of dollars each year. Current regulatory systems worldwide are over-whelmed with the increasing volume of international trade. Trade in nursery stock, wood products, pallets and dunnage have proven the most common means of transport for exotic forest pests. Despite our best efforts, pests such as chestnut...

78 FR 73577 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-06

...)(ii). Overview Currently, the Exchange's Risk Monitor Mechanism operates by the System maintaining a... Makers and other Users with greater control and flexibility with respect to managing risk and the manner...'', in order to modify the risk monitoring functionality offered to all Users \\5\\ of the BATS equity...

Battery condenser system total particulate emission factors and rates for cotton gins

USDA-ARS?s Scientific Manuscript database

This manuscript is part of a series of manuscripts that characterize cotton gin emissions from the standpoint of stack sampling. The impetus behind this project was the urgent need to collect additional cotton gin emissions data to address current regulatory issues. A key component of this study was...

Battery condenser system PM10 emission factors and rates for cotton gins

USDA-ARS?s Scientific Manuscript database

This manuscript is part of a series of manuscripts that to characterize cotton gin emissions from the standpoint of stack sampling. The impetus behind this project was the urgent need to collect additional cotton gin emissions data to address current regulatory issues. A key component of this study ...

Battery condenser system total particulate emission factors and rates for cotton gins: Method 17

USDA-ARS?s Scientific Manuscript database

This manuscript is part of a series of manuscripts that characterize cotton gin emissions from the standpoint of stack sampling. The impetus behind this project was the urgent need to collect additional cotton gin emissions data to address current regulatory issues. A key component of this study was...

76 FR 5636 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-01

... Commission, and all written communications relating to the proposed rule change between the Commission and... 11.9(b)(3)(a)-(r). Currently, the fee schedule has the following descriptions of routing strategies... time without notice. The System routing options are described in more detail below. The ROUC strategy...

76 FR 13638 - Ensuring the Safety of Imported Foods and Animal Feed: Comparability of Food Safety Systems and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Practices of Foreign Countries; Public Hearing; Request for Comments AGENCY: Food and Drug Administration... regulators in other countries regarding the regulatory policies, practices, and programs they currently use to ensure the safety of foods and animal feed imported into their countries. In a separate notice...

Development of archetypes for non-ranking classification and comparison of European National Health Technology Assessment systems.

PubMed

Allen, Nicola; Pichler, Franz; Wang, Tina; Patel, Sundip; Salek, Sam

2013-12-01

European countries are increasingly utilising health technology assessment (HTA) to inform reimbursement decision-making. However, the current European HTA environment is very diverse, and projects are already underway to initiate a more efficient and aligned HTA practice within Europe. This study aims to identify a non-ranking method for classifying the diversity of European HTA agencies process and the organisational architecture of the national regulatory review to reimbursement systems. Using a previously developed mapping methodology, this research created process maps to describe national processes for regulatory review to reimbursement for 33 European jurisdictions. These process maps enabled the creation of 2 HTA taxonomic sets. The confluence of the two taxonomic sets was subsequently cross-referenced to identify 10 HTA archetype groups. HTA is a young, rapidly evolving field and it can be argued that optimal practices for performing HTA are yet to emerge. Therefore, a non-ranking classification approach could objectively characterise and compare the diversity observed in the current European HTA environment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Analytical quality by design: a tool for regulatory flexibility and robust analytics.

PubMed

Peraman, Ramalingam; Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT).

Analytical Quality by Design: A Tool for Regulatory Flexibility and Robust Analytics

PubMed Central

Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT). PMID:25722723

Strengthening the Canadian alcohol advertising regulatory system.

PubMed

Heung, Carly M; Rempel, Benjamin; Krank, Marvin

2012-05-24

Research evidence points to harmful effects from alcohol advertising among children and youth. In particular, exposure to alcohol advertising has been associated with adolescents drinking both earlier and heavier. Although current federal and provincial guidelines have addressed advertising practices to prevent underage drinking, practice has not been supported by existing policy. While protective measures such as social marketing campaigns have the potential for counteracting the effects from alcohol advertising, the effectiveness of such measures can be easily drowned out with increasing advertising activities from the alcohol industry, especially without effective regulation. Research reviewed by the European Focus on Alcohol Safe Environment (FASE) Project has identified a set of key elements that are necessary to make alcohol advertising policy measures effective at protecting children and youth from the harmful effects of alcohol marketing. Using these key elements as an evaluation framework, there are critical components in the Canadian alcohol advertising regulatory system that clearly require strengthening. To protect impressionable children and youth against the harmful effects of alcohol advertising, 13 recommendations to strengthen current alcohol advertising regulations in Canada are provided for Canadian policy-makers, advertising standard agencies, and public health groups.

Making the Implicit Explicit: Towards an Assurance Case for DO-178C

NASA Technical Reports Server (NTRS)

Holloway, C. Michael

2013-01-01

For about two decades, compliance with Software Considerations in Airborne Systems and Equipment Certification (DO-178B) has been the primary means for receiving regulatory approval for using software on commercial airplanes. A new edition of the standard, DO-178C, was published in December 2011, and regulatory bodies have started the process towards recognizing this edition. The stated purpose of DO-178C remains unchanged from its predecessor: providing guidance “for the production of software for airborne systems and equipment that performs its intended function with a level of confidence in safety that complies with airworthiness requirements.” Within the text of the guidance, little or no rationale is given for how a particular objective or collection of objectives contributes to achieving this purpose. Thus the assurance case for the document is implicit. This paper discusses a current effort to make the implicit explicit. In particular, the paper describes the current status of the research seeking to identify the specific arguments contained in, or implied by, the DO-178C guidance that implicitly justify the assumption that the document meets its stated purpose.

Legal and regulatory aspects of prescribing and marketing emergency contraception in Nigeria.

PubMed

Adekunle, A O; Babarinsa, I A; Akinyemi, Z; Okediran, A Y

2001-01-01

Emergency contraception remains so little used or understood and the lack of its awareness can be traced to a myriad of factors including legal and regulatory obstacles. The aim of this study was to determine the legal and regulatory aspects of dispensing or marketing a contraceptive method for reasons (especially emergency purposes) other than stated by the manufacturers. The existing drugs' and devices' regulatory systems in Nigeria, especially those governing family planning methods, were reviewed. A questionnaire was administered to 363 health workers, comprising of physicians, pharmacists, nurses and midwives, to determine the implications of dispensing some currently available oral contraceptives (OCs) for emergency purposes despite the fact that there is no explicit description of emergency use in the labelling of such drugs. In addition, in-depth interviews were conducted with regulatory bodies. It was observed that, with the exception of Postinor, the drug manufacturers' leaflets did not indicate that they could be used for emergency contraceptive purposes. Although 64.5% of the healthcare providers were aware that OCs and intrauterine contraceptive devices (IUCDs) can be used for emergency purposes, 42.1% actually prescribed or recommended them. Many health workers (62.3%) were unaware of any legal implication with regards to prescribing unregistered drugs in Nigeria. The existing guidelines stipulate that a manufacturer or marketer should 're-register' a product if a new indication or use not contained in the initial application was found later. To satisfy legal requirements, it does appear that the currently available OCs and IUCDs in Nigeria must be labelled and registered for emergency contraceptive purposes.

Regulating the for-profit private healthcare providers towards universal health coverage: A qualitative study of legal and organizational framework in Mongolia.

PubMed

Tsevelvaanchig, Uranchimeg; Narula, Indermohan S; Gouda, Hebe; Hill, Peter S

2018-01-01

Regulating the behavior of private providers in the context of mixed health systems has become increasingly important and challenging in many developing countries moving towards universal health coverage including Mongolia. This study examines the current regulatory architecture for private healthcare in Mongolia exploring its role for improving accessibility, affordability, and quality of private care and identifies gaps in policy design and implementation. Qualitative research methods were used including documentary review, analysis, and in-depth interviews with 45 representatives of key actors involved in and affected by regulations in Mongolia's mixed health system, along with long-term participant observation. There has been extensive legal documentation developed regulating private healthcare, with specific organizations assigned to conduct health regulations and inspections. However, the regulatory architecture for healthcare in Mongolia is not optimally designed to improve affordability and quality of private care. This is not limited only to private care: important regulatory functions targeted to quality of care do not exist at the national level. The imprecise content and details of regulations in laws inviting increased political interference, governance issues, unclear roles, and responsibilities of different government regulatory bodies have contributed to failures in implementation of existing regulations. Copyright © 2017 John Wiley & Sons, Ltd.

Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

PubMed

Wang, Ting; McAuslane, Neil; Liberti, Lawrence; Leufkens, Hubert; Hövels, Anke

2018-06-01

To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy. Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics. Seven regulatory and 8 HTA agencies from Australia, Canada, and Europe and 19 international companies developing innovative medicine responded to the survey. This study provided a snapshot of the current regulatory and HTA landscape. Changes made over the past 5 years were reflected in three main areas: there is an increasing interaction between regulatory and HTA agencies; current conditional regulatory approvals are not always linked with flexible HTA approaches; and companies are more supportive of joint scientific advice. Four types of evidentiary requirements were identified as building blocks for better alignment: acceptable primary end points, inclusion of an active comparator, use of patient-reported outcomes, and choice and use of surrogate end point. The study showed that the gap between regulatory and HTA requirements has narrowed over the past 5 years. All respondents supported synergy between regulatory and HTA stakeholders, and the study provided several recommendations on how to further improve evidentiary alignment including the provision of joint scientific advice, which was rated as a key strategy by both agencies and companies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Worldwide legislative challenges related to psychoactive drugs.

PubMed

Negrei, Carolina; Galateanu, Bianca; Stan, Miriana; Balalau, Cristian; Dumitru, Mircea Lucian Bogdan; Ozcagli, Eren; Fenga, Concettina; Kovatsi, Leda; Fragou, Domniki; Tsatsakis, Aristidis

2017-06-02

The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.

Data-driven integration of genome-scale regulatory and metabolic network models

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

Imam, Saheed; Schauble, Sascha; Brooks, Aaron N.

Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or moremore » network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. Lastly, in this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.« less

Data-driven integration of genome-scale regulatory and metabolic network models

DOE PAGES

Imam, Saheed; Schauble, Sascha; Brooks, Aaron N.; ...

2015-05-05

Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or moremore » network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. Lastly, in this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.« less

Toxicogenomics and the Regulatory Framework

EPA Science Inventory

Toxicogenomics presents regulatory agencies with the opportunity to revolutionize their analyses by enabling the collection of information on a broader range of responses than currently considered in traditional regulatory decision making. Analyses of genomic responses are expec...

Integrated Regulatory and Metabolic Networks of the Marine Diatom Phaeodactylum tricornutum Predict the Response to Rising CO 2 Levels

DOE PAGES

Levering, Jennifer; Dupont, Christopher L.; Allen, Andrew E.; ...

2017-02-14

Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean’s primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom’s metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels. This transcriptional regulatory network was integrated with a recently published genome-scale metabolic model of Phaeodactylum tricornutum to explore the connectivity of the regulatory network and sharedmore » metabolites. The integrated regulatory and metabolic model revealed highly connected modules within carbon and nitrogen metabolism. P. tricornutum’s response to rising carbon levels was analyzed by using the recent genome-scale metabolic model with cross comparison to experimental manipulations of carbon dioxide. Using a systems biology approach, we studied the response of the marine diatom Phaeodactylum tricornutum to changing atmospheric carbon concentrations on an ocean-wide scale. By integrating an available genome-scale metabolic model and a newly developed transcriptional regulatory network inferred from transcriptome sequencing expression data, we demonstrate that carbon metabolism and nitrogen metabolism are strongly connected and the genes involved are coregulated in this model diatom. These tight regulatory constraints could play a major role during the adaptation of P. tricornutum to increasing carbon levels. The transcriptional regulatory network developed can be further used to study the effects of different environmental perturbations on P. tricornutum’s metabolism.« less

Integrated Regulatory and Metabolic Networks of the Marine Diatom Phaeodactylum tricornutum Predict the Response to Rising CO 2 Levels

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

Levering, Jennifer; Dupont, Christopher L.; Allen, Andrew E.

Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean’s primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom’s metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels. This transcriptional regulatory network was integrated with a recently published genome-scale metabolic model of Phaeodactylum tricornutum to explore the connectivity of the regulatory network and sharedmore » metabolites. The integrated regulatory and metabolic model revealed highly connected modules within carbon and nitrogen metabolism. P. tricornutum’s response to rising carbon levels was analyzed by using the recent genome-scale metabolic model with cross comparison to experimental manipulations of carbon dioxide. Using a systems biology approach, we studied the response of the marine diatom Phaeodactylum tricornutum to changing atmospheric carbon concentrations on an ocean-wide scale. By integrating an available genome-scale metabolic model and a newly developed transcriptional regulatory network inferred from transcriptome sequencing expression data, we demonstrate that carbon metabolism and nitrogen metabolism are strongly connected and the genes involved are coregulated in this model diatom. These tight regulatory constraints could play a major role during the adaptation of P. tricornutum to increasing carbon levels. The transcriptional regulatory network developed can be further used to study the effects of different environmental perturbations on P. tricornutum’s metabolism.« less

75 FR 22868 - Withdrawal of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

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

Application of Microprocessor-Based Equipment in Nuclear Power Plants - Technical Basis for a Qualification Methodology

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

Korsah, K.

This document (1) summarizes the most significant findings of the ''Qualification of Advanced Instrumentation and Control (I&C) Systems'' program initiated by the Nuclear Regulatory Commission (NRC); (2) documents a comparative analysis of U.S. and European qualification standards; and (3) provides recommendations for enhancing regulatory guidance for environmental qualification of microprocessor-based safety-related systems. Safety-related I&C system upgrades of present-day nuclear power plants, as well as I&C systems of Advanced Light-Water Reactors (ALWRs), are expected to make increasing use of microprocessor-based technology. The Nuclear Regulatory Commission (NRC) recognized that the use of such technology may pose environmental qualification challenges different from current,more » analog-based I&C systems. Hence, it initiated the ''Qualification of Advanced Instrumentation and Control Systems'' program. The objectives of this confirmatory research project are to (1) identify any unique environmental-stress-related failure modes posed by digital technologies and their potential impact on the safety systems and (2) develop the technical basis for regulatory guidance using these findings. Previous findings from this study have been documented in several technical reports. This final report in the series documents a comparative analysis of two environmental qualification standards--Institute of Electrical and Electronics Engineers (IEEE) Std 323-1983 and International Electrotechnical Commission (IEC) 60780 (1998)--and provides recommendations for environmental qualification of microprocessor-based systems based on this analysis as well as on the findings documented in the previous reports. The two standards were chosen for this analysis because IEEE 323 is the standard used in the U.S. for the qualification of safety-related equipment in nuclear power plants, and IEC 60780 is its European counterpart. In addition, the IEC document was published in 1998, and should reflect any new qualification concerns, from the European perspective, with regard to the use of microprocessor-based safety systems in power plants.« less

[EU law on marketing authorization of medicines. History, current state of development and perspectives].

PubMed

Nettesheim, Martin

2008-07-01

The article describes the development of EU policies and regulations on the marketing authorization of medicines. First, it describes the changing perspective of the EU towards the regulation of such authorizations. While its original focus was on the liberalization of national markets, it has today assumed overarching political responsibility for the development and marketing of medicines. Second, the article describes the current, rather fragmented regulatory system. Finally, political perspectives on the integration of markets for medicines are developed.

Direct broadcast satellite-radio market, legal, regulatory, and business considerations

NASA Technical Reports Server (NTRS)

Sood, Des R.

1991-01-01

A Direct Broadcast Satellite-Radio (DBS-R) System offers the prospect of delivering high quality audio broadcasts to large audiences at costs lower than or comparable to those incurred using the current means of broadcasting. The maturation of mobile communications technologies, and advances in microelectronics and digital signal processing now make it possible to bring this technology to the marketplace. Heightened consumer interest in improved audio quality coupled with the technological and economic feasibility of meeting this demand via DBS-R make it opportune to start planning for implementation of DBS-R Systems. NASA-Lewis and the Voice of America as part of their on-going efforts to improve the quality of international audio broadcasts, have undertaken a number of tasks to more clearly define the technical, marketing, organizational, legal, and regulatory issues underlying implementation of DBS-R Systems. The results and an assessment is presented of the business considerations underlying the construction, launch, and operation of DBS-R Systems.

Direct broadcast satellite-radio market, legal, regulatory, and business considerations

NASA Astrophysics Data System (ADS)

Sood, Des R.

1991-03-01

A Direct Broadcast Satellite-Radio (DBS-R) System offers the prospect of delivering high quality audio broadcasts to large audiences at costs lower than or comparable to those incurred using the current means of broadcasting. The maturation of mobile communications technologies, and advances in microelectronics and digital signal processing now make it possible to bring this technology to the marketplace. Heightened consumer interest in improved audio quality coupled with the technological and economic feasibility of meeting this demand via DBS-R make it opportune to start planning for implementation of DBS-R Systems. NASA-Lewis and the Voice of America as part of their on-going efforts to improve the quality of international audio broadcasts, have undertaken a number of tasks to more clearly define the technical, marketing, organizational, legal, and regulatory issues underlying implementation of DBS-R Systems. The results and an assessment is presented of the business considerations underlying the construction, launch, and operation of DBS-R Systems.

Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope?⊗

PubMed Central

Youan, Bi-Botti C.

2010-01-01

The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

Power Delivery from an Actual Thermoelectric Generation System

NASA Astrophysics Data System (ADS)

Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

2014-06-01

Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

78 FR 16346 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

... Procedures and the RTRS Users Manual. Current Form RTRS, which dealers must use to submit information to the MSRB pursuant to Rule G-14(b)(iv), requires dealers to provide certain information to ensure that their... information from the filer's MSRB Gateway system \\6\\ account to pre-populate certain sections of revised Form...

78 FR 50477 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... them in sequence for entry into the System for execution. Each of Phlx's current connection offerings... connectivity and installation fees for a 10Gb Ultra low latency fiber connection option, and provide a waiver... bandwidth options for connectivity to the Exchange, including a 40Gb fiber connection, a 10Gb fiber...

78 FR 50132 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... into the System for execution. Each of BX's current connection offerings uses different switches... 10Gb Ultra low latency fiber connection option, and provide a waiver of installation fees for... to the Exchange, including a 40Gb fiber connection, a 10Gb fiber connection, a 1Gb fiber connection...

77 FR 17534 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-26

... Association (``SIFMA'') formed the MMI Blue-Sky Task Force (``Task Force'') to address systemic and unique... processing. The Task Force, along other money market industry members,\\8\\ determined that DTC's current MMI... amount or proceeds after the 3 p.m. E.T. deadline for RTP instructions.\\9\\ Accordingly, DTC is proposing...

75 FR 53008 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

..., and (ii) terminate the opening process when away markets become crossed during the opening process. A new opening process for the affected series would commence at the time the Away Best Bid/Offer (``ABBO... PHLX XL system currently calculates the OQR without regard to away market(s) in the affected series...

78 FR 79042 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... time period of the Pilot Program,\\4\\ which is currently scheduled to expire on December 31, 2013... that it is designed to prevent fraudulent and manipulative acts and practices, to promote just and... and a national market system. The Exchange believes that the Pilot Program promotes just and equitable...

78 FR 49586 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... Market Maker Standard quote server as a gateway for communicating eQuotes to MIAX. Because of the... connect the Limited Service Ports to independent servers that host their eQuote and purge functionality... same server for all of their Market Maker quoting activity. Currently, Market Makers in the MIAX System...

Battery condenser system PM10 emission factors and rates for cotton gins: Method 201A PM10 sizing cyclones

USDA-ARS?s Scientific Manuscript database

This manuscript is part of a series of manuscripts that to characterize cotton gin emissions from the standpoint of stack sampling. The impetus behind this project was the urgent need to collect additional cotton gin emissions data to address current regulatory issues. A key component of this study ...

Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

PubMed Central

Ju, Wenjun; Brosius, Frank C.

2010-01-01

Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762

Waste management technology development and demonstration programs at Brookhaven National Laboratory

NASA Technical Reports Server (NTRS)

Kalb, Paul D.; Colombo, Peter

1991-01-01

Two thermoplastic processes for improved treatment of radioactive, hazardous, and mixed wastes were developed from bench scale through technology demonstration: polyethylene encapsulation and modified sulfur cement encapsulation. The steps required to bring technologies from the research and development stage through full scale implementation are described. Both systems result in durable waste forms that meet current Nuclear Regulatory Commission and Environmental Protection Agency regulatory criteria and provide significant improvements over conventional solidification systems such as hydraulic cement. For example, the polyethylene process can encapsulate up to 70 wt pct. nitrate salt, compared with a maximum of about 20 wt pct. for the best hydraulic cement formulation. Modified sulfur cement waste forms containing as much as 43 wt pct. incinerator fly ash were formulated, whereas the maximum quantity of this waste in hydraulic cement is 16 wt pct.

30th Annual Drug Information Association (DIA) Europe 2018 (April 17-19, 2018 - Basel, Switzerland).

PubMed

Hamaui Cuadrado, S; Guinart Vidal, M

2018-05-01

The Drug Information Association (DIA) Europe held its annual meeting from April 17-19, 2018, in Basel, Switzerland. The key topics discussed in the 3-day meeting were related to pharmacovigilance, clinical development, patient engagement, data and data standards, preclinical development and early-phase clinical research, regulatory science, translational medicine and science, and value and access. The program was principally focused on the current opportunities and future landscape of the healthcare system as a result of the increasingly innovative technologies and effective utilization of big data. In addition, the critical need for collaboration and partnership between all the stakeholders of the healthcare system was highlighted. This report covers some of the regulatory sessions presented at the meeting in which regulators, payers, industry and patients presented their perspectives for discussion. Copyright 2018 Clarivate Analytics.

From maturity to value-added innovation: lessons from the pharmaceutical and agro-biotechnology industries.

PubMed

Mittra, James; Tait, Joyce; Wield, David

2011-03-01

The pharmaceutical and agro-biotechnology industries have been confronted by dwindling product pipelines and rapid developments in life sciences, thus demanding a strategic rethink of conventional research and development. Despite offering both industries a solution to the pipeline problem, the life sciences have also brought complex regulatory challenges for firms. In this paper, we comment on the response of these industries to the life science trajectory, in the context of maturing conventional small-molecule product pipelines and routes to market. The challenges of managing transition from maturity to new high-value-added innovation models are addressed. Furthermore, we argue that regulation plays a crucial role in shaping the innovation systems of both industries, and as such, we suggest potentially useful changes to the current regulatory system. Copyright © 2010 Elsevier Ltd. All rights reserved.

HIV testing updates and challenges: when regulatory caution and public health imperatives collide.

PubMed

Branson, Bernard M

2015-03-01

Numerous improvements in HIV testing technology led recently to the first revision of recommendations for diagnostic laboratory testing in the USA in 25 years. Developments in HIV testing continue to produce tests that identify HIV infection earlier with faster turnaround times for test results. These play an important role in identifying HIV infection during the highly infectious acute phase, which has implication for both patient management and public health interventions to control the spread of HIV. Access to these developments, however, is often delayed by the regulatory apparatus for approval and oversight of HIV testing in the USA. This article summarizes recent developments in HIV diagnostic testing technology, outlines their implications for clinical management and public health, describes current systems of regulatory oversight for HIV testing in the USA, and proposes alternatives that could expedite access to improved tests as they become available.

Recent regulatory experience of low-Btu coal gasification. Volume III. Supporting case studies

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

Ackerman, E.; Hart, D.; Lethi, M.

The MITRE Corporation conducted a five-month study for the Office of Resource Applications in the Department of Energy on the regulatory requirements of low-Btu coal gasification. During this study, MITRE interviewed representatives of five current low-Btu coal gasification projects and regulatory agencies in five states. From these interviews, MITRE has sought the experience of current low-Btu coal gasification users in order to recommend actions to improve the regulatory process. This report is the third of three volumes. It contains the results of interviews conducted for each of the case studies. Volume 1 of the report contains the analysis of themore » case studies and recommendations to potential industrial users of low-Btu coal gasification. Volume 2 contains recommendations to regulatory agencies.« less

Distinguishing between the Permeability Relationships with Absorption and Metabolism To Improve BCS and BDDCS Predictions in Early Drug Discovery

PubMed Central

2015-01-01

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug–drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption. PMID:24628254

Distinguishing between the permeability relationships with absorption and metabolism to improve BCS and BDDCS predictions in early drug discovery.

PubMed

Larregieu, Caroline A; Benet, Leslie Z

2014-04-07

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug-drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption.

A perspective on the benefit-risk assessment for new and emerging pharmaceuticals in Japan.

PubMed

Tanimoto, Tetsuya

2015-01-01

The universal health care system in Japan is facing a historical turning point as a result of the increasing fiscal burden, rapidly aging society, and a decreasing population. To understand the challenges and opportunities in the Japanese pharmaceutical market, which occupies one tenth of the global share, this review highlights several issues related to the benefit-risk assessment that is unique to the modern Japanese society: 1) regulatory system for new drug development; 2) health hazards related to pharmaceuticals ("Yakugai" in Japanese); 3) drug lag; 4) problems and controversies in the vaccination policy; and 5) clinical study misconduct. The regulatory process places a significant importance on Japanese data collection regardless of data accumulation from other countries. Because Yakugai has repeatedly caused tragedies and social disputes historically, the regulatory judgments generally tend to be more prudential when safety concerns are raised for new and emerging pharmaceuticals. Such a regulatory system has caused more than several years of approval delays compared to delays in other countries. The problem of drug lag still lingers on despite several regulatory system revisions, while the solution is incompatible with the elimination of Yakugai because the lag potentially reduces the risk of unpredictable adverse events. The Japanese vaccination policy has also received a lot of criticism, and needs improvements so that the decision-making process can be more transparent and scientifically based. Additionally, repeated clinical study misconduct damaged the reputation of Japanese clinical studies with unnecessary defrayment in health insurance; therefore, the medical community must change its inappropriate relationship with the industry. The problems surrounding pharmaceuticals are related to centralized, strict drug pricing control under the universal health coverage. Although the current government attempts to facilitate innovative research and development of novel therapeutics in Japan, further reforms should be explored for patients who need new and emerging pharmaceuticals.

A perspective on the benefit-risk assessment for new and emerging pharmaceuticals in Japan

PubMed Central

Tanimoto, Tetsuya

2015-01-01

The universal health care system in Japan is facing a historical turning point as a result of the increasing fiscal burden, rapidly aging society, and a decreasing population. To understand the challenges and opportunities in the Japanese pharmaceutical market, which occupies one tenth of the global share, this review highlights several issues related to the benefit-risk assessment that is unique to the modern Japanese society: 1) regulatory system for new drug development; 2) health hazards related to pharmaceuticals (“Yakugai” in Japanese); 3) drug lag; 4) problems and controversies in the vaccination policy; and 5) clinical study misconduct. The regulatory process places a significant importance on Japanese data collection regardless of data accumulation from other countries. Because Yakugai has repeatedly caused tragedies and social disputes historically, the regulatory judgments generally tend to be more prudential when safety concerns are raised for new and emerging pharmaceuticals. Such a regulatory system has caused more than several years of approval delays compared to delays in other countries. The problem of drug lag still lingers on despite several regulatory system revisions, while the solution is incompatible with the elimination of Yakugai because the lag potentially reduces the risk of unpredictable adverse events. The Japanese vaccination policy has also received a lot of criticism, and needs improvements so that the decision-making process can be more transparent and scientifically based. Additionally, repeated clinical study misconduct damaged the reputation of Japanese clinical studies with unnecessary defrayment in health insurance; therefore, the medical community must change its inappropriate relationship with the industry. The problems surrounding pharmaceuticals are related to centralized, strict drug pricing control under the universal health coverage. Although the current government attempts to facilitate innovative research and development of novel therapeutics in Japan, further reforms should be explored for patients who need new and emerging pharmaceuticals. PMID:25848223

Defining the pharmaceutical system to support proactive drug safety.

PubMed

Lewis, Vicki R; Hernandez, Angelica; Meadors, Margaret

2013-02-01

The military, aviation, nuclear, and transportation industries have transformed their safety records by using a systems approach to safety and risk mitigation. This article creates a preliminary model of the U.S. pharmaceutical system using available literature including academic publications, policies, and guidelines established by regulatory bodies and drug industry trade publications. Drawing from the current literature, the goals, roles, and individualized processes of pharmaceutical subsystems will be defined. Defining the pharmaceutical system provides a vehicle to assess and address known problems within the system, and provides a means to conduct proactive risk analyses, which would create significant pharmaceutical safety advancement.

Interpreting MSHA citations through the lens of occupational health and safety management systems: investigating their impact on mine injuries and illnesses 2003-2010.

PubMed

Yorio, Patrick L; Willmer, Dana R; Haight, Joel M

2014-08-01

Since the late 1980s, the U.S. Department of Labor has considered regulating a systems approach to occupational health and safety management. Recently, a health and safety management systems (HSMS) standard has returned to the regulatory agenda of both the Occupational Safety and Health Administration (OSHA) and the Mine Safety and Health Administration (MSHA). Because a mandated standard has implications for both industry and regulating bodies alike, it is imperative to gain a greater understanding of the potential effects that an HSMS regulatory approach can have on establishment-level injuries and illnesses. Through the lens of MSHA's regulatory framework, we first explore how current enforcement activities align with HSMS elements. Using MSHA data for the years 2003-2010, we then analyze the relationship between various types of enforcement activities (e.g., total number of citations, total penalty amount, and HSMS-aligned citations) and mine reportable injuries. Our findings show that the reduction in mine reportable injuries predicted by increases in MSHA enforcement ranges from negligible to 18%. The results suggest that the type and focus of the enforcement activity may be more important for accident reduction than the total number of citations issued and the associated penalty amount. © 2014 Society for Risk Analysis.

77 FR 48177 - Fuel Oil Systems for Emergency Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

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

Regulatory ozone modeling: status, directions, and research needs.

PubMed Central

Georgopoulos, P G

1995-01-01

The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAQSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAQSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model's performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. Selected interim results from diagnostic analyses, which are performed as a component of the regulatory ozone modeling process for the Philadelphia-New Jersey region, are also presented to provide some specific examples related to the general issues discussed in this work. Finally, research needs related to a) the evaluation and refinement of regulatory ozone modeling, b) the characterization of uncertainty in photochemical modeling, and c) the improvement of the model-based ozone-attainment demonstration process are presented to identify future directions in this area. Images Figure 7. Figure 7. Figure 7. Figure 8. Figure 9. PMID:7614934

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

The European Regulatory Environment of RNA-Based Vaccines.

PubMed

Hinz, Thomas; Kallen, Kajo; Britten, Cedrik M; Flamion, Bruno; Granzer, Ulrich; Hoos, Axel; Huber, Christoph; Khleif, Samir; Kreiter, Sebastian; Rammensee, Hans-Georg; Sahin, Ugur; Singh-Jasuja, Harpreet; Türeci, Özlem; Kalinke, Ulrich

2017-01-01

A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.

[Inconsistencies between building regulations in force in Italy for indoor environment and wellness factors].

PubMed

Faggioli, A; Capasso, L

2015-01-01

Indoor environment is one of major health determinants, and the regulations that set the sanitary requirements are of primary importance for the protection of public health. The authors analyse the critical aspects of the complex Italian regulatory system, starting from the EU regulations, through national and regional laws, and finally the municipal regulations. They underline the need for more uniformity and clarity in the determination of health standards, as well as for a simplification of the existing legislation. Moreover, they highlight the importance of controlling and monitoring indoor environment, currently almost completely absent in Italy due to the effects of the regulatory changes of the latest years.

Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-β and retinoic acid

PubMed Central

Fleissner, Diana; Frede, Annika; Knott, Markus; Knuschke, Torben; Geffers, Robert; Hansen, Wiebke; Dobos, Gustav; Langhorst, Jost; Buer, Jan; Westendorf, Astrid M

2011-01-01

The intestinal immune system is constantly challenged by foreign antigens and commensal bacteria. Therefore, proper control of the intestinal microenvironment is required. One important arm of this regulatory network consists of regulatory T cells. In contrast to CD4+ Foxp3+ regulatory T cells, which have been well characterized, immunomodulatory CD8+ T cells that express Foxp3 are less well defined in terms of their generation and function. Failures of these regulatory mechanisms contribute to the development of inflammatory bowel disease. In this study we demonstrate that the frequency of CD8+ Foxp3+ T cells is reduced in the peripheral blood of patients with ulcerative colitis. As these cells might play a currently underestimated role in the maintenance of intestinal homeostasis, we have investigated human and murine CD8+ Foxp3+ T cells generated by stimulating naive CD8+ T cells in the presence of transforming growth factor-β and retinoic acid, mediators that are abundantly produced in the intestinal mucosa. These CD8+ Foxp3+ fully competent regulatory T cells show strong expression of regulatory molecules CD25, Gpr83 and CTLA-4 and exhibit cell–cell contact-dependent immunosuppressive activity in vitro. Our study illustrates a previously unappreciated critical role of CD8+ Foxp3+ T cells in controlling potentially dangerous T cells and in the maintenance of intestinal homeostasis. PMID:21711349

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.

The PathoYeastract database: an information system for the analysis of gene and genomic transcription regulation in pathogenic yeasts.

PubMed

Monteiro, Pedro Tiago; Pais, Pedro; Costa, Catarina; Manna, Sauvagya; Sá-Correia, Isabel; Teixeira, Miguel Cacho

2017-01-04

We present the PATHOgenic YEAst Search for Transcriptional Regulators And Consensus Tracking (PathoYeastract - http://pathoyeastract.org) database, a tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in the pathogenic yeasts Candida albicans and C. glabrata Upon data retrieval from hundreds of publications, followed by curation, the database currently includes 28 000 unique documented regulatory associations between transcription factors (TF) and target genes and 107 DNA binding sites, considering 134 TFs in both species. Following the structure used for the YEASTRACT database, PathoYeastract makes available bioinformatics tools that enable the user to exploit the existing information to predict the TFs involved in the regulation of a gene or genome-wide transcriptional response, while ranking those TFs in order of their relative importance. Each search can be filtered based on the selection of specific environmental conditions, experimental evidence or positive/negative regulatory effect. Promoter analysis tools and interactive visualization tools for the representation of TF regulatory networks are also provided. The PathoYeastract database further provides simple tools for the prediction of gene and genomic regulation based on orthologous regulatory associations described for other yeast species, a comparative genomics setup for the study of cross-species evolution of regulatory networks. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

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

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

2011-07-01

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

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

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

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

2011-01-01

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

Organomatics and organometrics: Novel platforms for long-term whole-organ culture

PubMed Central

Bruinsma, Bote G.; Yarmush, Martin L.; Uygun, Korkut

2014-01-01

Organ culture systems are instrumental as experimental whole-organ models of physiology and disease, as well as preservation modalities facilitating organ replacement therapies such as transplantation. Nevertheless, a coordinated system of machine perfusion components and integrated regulatory control has yet to be fully developed to achieve long-term maintenance of organ function ex vivo. Here we outline current strategies for organ culture, or organomatics, and how these systems can be regulated by means of computational algorithms, or organometrics, to achieve the organ culture platforms anticipated in modern-day biomedicine. PMID:25035864

The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.

PubMed

Barzantny, Helena; Schröder, Jasmin; Strotmeier, Jasmin; Fredrich, Eugenie; Brune, Iris; Tauch, Andreas

2012-06-15

Lipophilic corynebacteria are involved in the generation of volatile odorous products in the process of human body odor formation by degrading skin lipids and specific odor precursors. Therefore, these bacteria represent appropriate model systems for the cosmetic industry to examine axillary malodor formation on the molecular level. To understand the transcriptional control of metabolic pathways involved in this process, the transcriptional regulatory network of the lipophilic axilla isolate Corynebacterium jeikeium K411 was reconstructed from the complete genome sequence. This bioinformatic approach detected a gene-regulatory repertoire of 83 candidate proteins, including 56 DNA-binding transcriptional regulators, nine two-component systems, nine sigma factors, and nine regulators with diverse physiological functions. Furthermore, a cross-genome comparison among selected corynebacterial species of the taxonomic cluster 3 revealed a common gene-regulatory repertoire of 44 transcriptional regulators, including the MarR-like regulator Jk0257, which is exclusively encoded in the genomes of this taxonomical subline. The current network reconstruction comprises 48 transcriptional regulators and 674 gene-regulatory interactions that were assigned to five interconnected functional modules. Most genes involved in lipid degradation are under the combined control of the global cAMP-sensing transcriptional regulator GlxR and the LuxR-family regulator RamA, probably reflecting the essential role of lipid degradation in C. jeikeium. This study provides the first genome-scale in silico analysis of the transcriptional regulation of metabolism in a lipophilic bacterium involved in the formation of human body odor. Copyright © 2012 Elsevier B.V. All rights reserved.

Meeting Report: 2015 PDA Virus & TSE Safety Forum.

PubMed

Willkommen, Hannelore; Blümel, Johannes; Brorson, Kurt; Chen, Dayue; Chen, Qi; Gröner, Albrecht; Kreil, Thomas R; Ruffing, Michel; Ruiz, Sol; Scott, Dorothy; Silvester, Glenda

2016-01-01

The report provides a summary of the presentations at the Virus & TSE Safety Forum 2015 organized by the Parenteral Drug Association (PDA) and held in Cascais, Portugal, from 9 to 11 June, 2015. As with previous conferences of this series, the PDA Virus & TSE Safety Forum 2015 provided an excellent forum for the exchange of information and opinions between the industry, research organizations, and regulatory bodies. Regulatory updates on virus and TSE safety aspects illustrating current topics of discussion at regulatory agencies in Europe and the United States were provided; the conference covered emerging viruses and new virus detection systems that may be used for the investigation of human pathogenic viruses as well as the virus safety of cell substrates and of raw material of ovine/caprine or human origin. Progress of development and use of next-generation sequencing methods was shown by several examples. Virus clearance data illustrating the effectiveness of inactivation or removal methods were presented and data provided giving insight into the mechanism of action of these technologies. In the transmissible spongiform encephalopathy (TSE) part of the conference, the epidemiology of variant Creutzfeldt-Jakob disease was reviewed and an overview about diagnostic tests provided; current thinking about the spread and propagation of prions was presented and the inactivation of prions by disinfection (equipment) and in production of bovine-derived reagents (heparin) shown. The current report provides an overview about the outcomes of the 2015 PDA Virus & TSE Safety Forum, a unique event in this field. © PDA, Inc. 2016.

Accounting Profession: Oversight, Auditor Independence, and Financial Reporting Issues

DTIC Science & Technology

2002-05-03

oversight of the accounting profession, auditor independence, and selected financial reporting matters. The sudden and largely unexpected bankruptcy of the...Enron Corporation (Enron) and other large corporations financial reporting restatements have raised questions about the soundness of the current self...regulatory and financial reporting systems and resulted in substantial losses to employees, shareholders, and other investors. These events have also

77 FR 47455 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

.... (``Bloomberg''), FactSet Research Systems, Inc. (``FactSet'') and Thomson Reuters (``Reuters''). Real time data... reasonably related to the current value of the underlying index at the time such series are first opened for... to which such series relates at or about the time such series of options is first opened for trading...

75 FR 77932 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... the position even at the $1 cabinet price (e.g., the series might be quoted no bid). \\5\\ Currently the... (``COATS'') requirements of Exchange Rule 955NY. Order Format and System Entry Requirements. However, the... as the COATS data is maintained. In this regard, all transactions for less than $1 must be reported...

75 FR 1109 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-08

.... \\5\\ A ``pair'' of ports refers to one port at the site of the Exchange's primary data center... for physical ports used to connect to the Exchange's system for order entry and receipt of data from... receipt of Exchange data,\\4\\ but does not currently charge for the ``physical'' ports needed to connect to...

Successful validation of in vitro methods in toxicology by ZEBET, the National Centre for Alternatives in Germany at the BfR (Federal Institute for Risk Assessment).

PubMed

Spielmann, Horst; Grune, Barbara; Liebsch, Manfred; Seiler, Andrea; Vogel, Richard

2008-06-01

A short description of the history of the 3Rs concept is given, which was developed as the scientific concept to refine, reduce and replace animal experiments by Russel and Burch more than 40 years ago. In addition, the legal framework in Europe for developing alternatives to animal experiments is given and the current status of in vitro systems in pharmacology and toxicology is described including an update on metabolising systems. The decrease in experimental animal numbers during the past decade in Europe is illustrated by the situation in Germany and the contribution of international harmonisation of test guidelines on reducing animal numbers in regulatory testing is described. A review of the development of the principles of experimental validation is given and the 3T3 NRU in vitro phototoxicity test is used as an example for a successful validation study, which led to the acceptance of the first in vitro toxicity test for regulatory purposes by the OECD. Finally, the currently accepted alternative methods for standardisation and safety testing of drugs, biologicals and medical devices are summarised.

Baseline Evaluations to Support Control Room Modernization at Nuclear Power Plants

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

Boring, Ronald L.; Joe, Jeffrey C.

2015-02-01

For any major control room modernization activity at a commercial nuclear power plant (NPP) in the U.S., a utility should carefully follow the four phases prescribed by the U.S. Nuclear Regulatory Commission in NUREG-0711, Human Factors Engineering Program Review Model. These four phases include Planning and Analysis, Design, Verification and Validation, and Implementation and Operation. While NUREG-0711 is a useful guideline, it is written primarily from the perspective of regulatory review, and it therefore does not provide a nuanced account of many of the steps the utility might undertake as part of control room modernization. The guideline is largely summative—intendedmore » to catalog final products—rather than formative—intended to guide the overall modernization process. In this paper, we highlight two crucial formative sub-elements of the Planning and Analysis phase specific to control room modernization that are not covered in NUREG-0711. These two sub-elements are the usability and ergonomics baseline evaluations. A baseline evaluation entails evaluating the system as-built and currently in use. The usability baseline evaluation provides key insights into operator performance using the control system currently in place. The ergonomics baseline evaluation identifies possible deficiencies in the physical configuration of the control system. Both baseline evaluations feed into the design of the replacement system and subsequent summative benchmarking activities that help ensure that control room modernization represents a successful evolution of the control system.« less

Intercellular and systemic spread of RNA and RNAi in plants.

PubMed

Nazim Uddin, Mohammad; Kim, Jae-Yean

2013-01-01

Plants possess dynamic networks of intercellular communication that are crucial for plant development and physiology. In plants, intercellular communication involves a combination of ligand-receptor-based apoplasmic signaling, and plasmodesmata and phloem-mediated symplasmic signaling. The intercellular trafficking of macromolecules, including RNAs and proteins, has emerged as a novel mechanism of intercellular communication in plants. Various forms of regulatory RNAs move over distinct cellular boundaries through plasmodesmata and phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also involved in development, nutrient homeostasis, gene silencing, pathogen defense, and many other physiological processes. However, the mechanism underlying macromolecular trafficking in plants remains poorly understood. Current progress made in RNA trafficking research and its biological relevance to plant development will be summarized. Diverse plant regulatory mechanisms of cell-to-cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs, and small RNAs, will also be discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Understanding genetic variation - the value of systems biology.

PubMed

Hütt, Marc-Thorsten

2014-04-01

Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. © 2013 The British Pharmacological Society.

Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.

PubMed

Carden, Tony; Goode, Natassia; Read, Gemma J M; Salmon, Paul M

2017-03-15

Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Australian Food Safety Policy Changes from a "Command and Control" to an "Outcomes-Based" Approach: Reflection on the Effectiveness of Its Implementation.

PubMed

Smith, James; Ross, Kirstin; Whiley, Harriet

2016-12-08

Foodborne illness is a global public health burden. Over the past decade in Australia, despite advances in microbiological detection and control methods, there has been an increase in the incidence of foodborne illness. Therefore improvements in the regulation and implementation of food safety policy are crucial for protecting public health. In 2000, Australia established a national food safety regulatory system, which included the adoption of a mandatory set of food safety standards. These were in line with international standards and moved away from a "command and control" regulatory approach to an "outcomes-based" approach using risk assessment. The aim was to achieve national consistency and reduce foodborne illness without unnecessarily burdening businesses. Evidence demonstrates that a risk based approach provides better protection for consumers; however, sixteen years after the adoption of the new approach, the rates of food borne illness are still increasing. Currently, food businesses are responsible for producing safe food and regulatory bodies are responsible for ensuring legislative controls are met. Therefore there is co-regulatory responsibility and liability and implementation strategies need to reflect this. This analysis explores the challenges facing food regulation in Australia and explores the rationale and evidence in support of this new regulatory approach.

Gene Regulatory Network Inferences Using a Maximum-Relevance and Maximum-Significance Strategy

PubMed Central

Liu, Wei; Zhu, Wen; Liao, Bo; Chen, Xiangtao

2016-01-01

Recovering gene regulatory networks from expression data is a challenging problem in systems biology that provides valuable information on the regulatory mechanisms of cells. A number of algorithms based on computational models are currently used to recover network topology. However, most of these algorithms have limitations. For example, many models tend to be complicated because of the “large p, small n” problem. In this paper, we propose a novel regulatory network inference method called the maximum-relevance and maximum-significance network (MRMSn) method, which converts the problem of recovering networks into a problem of how to select the regulator genes for each gene. To solve the latter problem, we present an algorithm that is based on information theory and selects the regulator genes for a specific gene by maximizing the relevance and significance. A first-order incremental search algorithm is used to search for regulator genes. Eventually, a strict constraint is adopted to adjust all of the regulatory relationships according to the obtained regulator genes and thus obtain the complete network structure. We performed our method on five different datasets and compared our method to five state-of-the-art methods for network inference based on information theory. The results confirm the effectiveness of our method. PMID:27829000

Australian Food Safety Policy Changes from a “Command and Control” to an “Outcomes-Based” Approach: Reflection on the Effectiveness of Its Implementation

PubMed Central

Smith, James; Ross, Kirstin; Whiley, Harriet

2016-01-01

Foodborne illness is a global public health burden. Over the past decade in Australia, despite advances in microbiological detection and control methods, there has been an increase in the incidence of foodborne illness. Therefore improvements in the regulation and implementation of food safety policy are crucial for protecting public health. In 2000, Australia established a national food safety regulatory system, which included the adoption of a mandatory set of food safety standards. These were in line with international standards and moved away from a “command and control” regulatory approach to an “outcomes-based” approach using risk assessment. The aim was to achieve national consistency and reduce foodborne illness without unnecessarily burdening businesses. Evidence demonstrates that a risk based approach provides better protection for consumers; however, sixteen years after the adoption of the new approach, the rates of food borne illness are still increasing. Currently, food businesses are responsible for producing safe food and regulatory bodies are responsible for ensuring legislative controls are met. Therefore there is co-regulatory responsibility and liability and implementation strategies need to reflect this. This analysis explores the challenges facing food regulation in Australia and explores the rationale and evidence in support of this new regulatory approach. PMID:27941657

The current status and future potential of personalized diagnostics: Streamlining a customized process.

PubMed

Richmond, Terri D

2008-01-01

Recent genetic discoveries and related developments in genomic techniques have led to the commercialization of novel diagnostic platforms for studying disease or gauging therapeutic outcomes in individual patients. This newly emerging field is called "personalized medicine," and uses the patient's genetic composition to tailor strategies for patient-specific disease detection, treatment, or prevention. Personalized diagnostic tests are used to detect patient-to-patient variations in gene or protein expression levels, which act as indicators for drug treatments or disease prognosis. In turn, medical professionals can better answer questions such as: "Who should be treated with which drug?" and "How should the treatment be administered?" The regulations governing personalized medicine can be complicated because they encompass in vitro diagnostic systems and laboratory tests as well as methods of disease treatment and patient care. Industry, academia, medicine, and the Food and Drug Administration (FDA) are all involved in the cultivation of the field: substantial collaborations between drug developers and regulatory authorities are required to consider and shape emerging regulations as personalized drug strategies mature. Some of the regulatory issues identified by industry and the FDA about personalized medicine and personalized diagnostics will be addressed. In addition, relevant collaborations, advances, and current and draft regulatory guidances will be discussed with respect to the future of personalized medicine.

Perspectives on Unmanned Aircraft Classification for Civil Airworthiness Standards

NASA Technical Reports Server (NTRS)

Maddalon, Jeffrey M.; Hayhurst, Kelly J.; Koppen, Daniel M.; Upchurch, Jason M.; Morris, A. Terry; Verstynen, Harry A.

2013-01-01

The use of unmanned aircraft in the National Airspace System (NAS) has been characterized as the next great step forward in the evolution of civil aviation. Although use of unmanned aircraft systems (UAS) in military and public service operations is proliferating, civil use of UAS remains limited in the United States today. This report focuses on one particular regulatory challenge: classifying UAS to assign airworthiness standards. This paper provides observations related to how the current regulations for classifying manned aircraft could apply to UAS.

The interaction between intellectual property and drug regulatory systems: global perspectives.

PubMed

Madden, Edward A

2007-02-01

Regulatory compliance in the development, production and sale of new drugs accounts for the largest single expense in bringing a drug product to market. To justify developmental and regulatory compliance costs, drug innovators turn to the intellectual property (IP) system to provide a means for securing returns on investment. Because the drug regulatory system in most countries operates in isolation of the IP system, one of the greatest challenges facing the pharmaceutical industry is the extent to which IP rights can be managed against an independent drug regulatory system. Many regulatory bodies in developed countries have sought to ensure a compromise between the rights of generic companies and IP owners by including safeguards in the regulatory framework, such as patent linking and data protection; however, these efforts are yet to be applied in some of the biggest potential drug markets in emerging economies.

Legal and regulatory responses to innovative treatment.

PubMed

Chan, Tracey Evans

2013-01-01

Developments in medical technology, healthcare delivery, and commercial interests in medicine have increased both the potential for conflicts of interest on the part of physicians, and doubts over the sufficiency of patient autonomy as a justification for administering innovative therapy. The legal and regulatory treatment of innovative therapy is therefore an important question, on which there is a current lack of consensus on a number of issues. This paper discusses recent developments in Singapore and uses them as a springboard to flesh out basic regulatory issues that arise from the deployment of innovative treatment: the distinction between innovative treatment and clinical research, the adequacy of the current post hoc scrutiny of innovative therapy under existing legal principles and the need for further specialised regulatory oversight.

Nanomedicines in gastroenterology and hepatology.

PubMed

Lamprecht, Alf

2015-04-01

Nanoscale systems are currently under investigation for multiple different diagnostic and therapeutic applications. These systems can be used to identify pathologically changed tissues or to selectively deliver drugs to these sites; both applications have an extremely high potential to ameliorate therapeutic outcomes for patients. Tissues as well as single cells can be targeted because of the small size of these systems, which enables enhanced diagnosis and increased specificity of therapy. Drug loads can be delivered directly to the site of action, which can result in a reduction in incidence and severity of adverse systemic effects. Several nano-based platform technologies are currently under investigation for use in therapeutic approaches, mainly for anti-inflammatory and anti-cancer therapies. Although many nanoscale systems show promising therapeutic outcomes in preclinical studies, only a limited number are ready for clinical use. This Review will discuss the diverse nanomaterials currently available and the first specific uses for select gastroenterological and hepatological pathologies. The discussion of diagnostic and therapeutic applications will consider realities of market introduction of these sometimes very complex systems in light of remaining regulatory challenges and hurdles for industrial production.

Biology-inspired Microphysiological System Approaches to Solve the Prediction Dilemma of Substance Testing

PubMed Central

Marx, Uwe; Andersson, Tommy B.; Bahinski, Anthony; Beilmann, Mario; Beken, Sonja; Cassee, Flemming R.; Cirit, Murat; Daneshian, Mardas; Fitzpatrick, Susan; Frey, Olivier; Gaertner, Claudia; Giese, Christoph; Griffith, Linda; Hartung, Thomas; Heringa, Minne B.; Hoeng, Julia; de Jong, Wim H.; Kojima, Hajime; Kuehnl, Jochen; Luch, Andreas; Maschmeyer, Ilka; Sakharov, Dmitry; Sips, Adrienne J. A. M.; Steger-Hartmann, Thomas; Tagle, Danilo A.; Tonevitsky, Alexander; Tralau, Tewes; Tsyb, Sergej; van de Stolpe, Anja; Vandebriel, Rob; Vulto, Paul; Wang, Jufeng; Wiest, Joachim; Rodenburg, Marleen; Roth, Adrian

2017-01-01

Summary The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-five experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale. PMID:27180100

Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol

PubMed Central

Klonoff, David C.; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A.; Arreaza-Rubin, Guillermo; Burk, Robert D.; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B.; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W.

2015-01-01

Background: Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. Methods: The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. Results: A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled “Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program” is attached as supplementary material. Conclusion: This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. PMID:26481642

Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol.

PubMed

Klonoff, David C; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A; Arreaza-Rubin, Guillermo; Burk, Robert D; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W

2016-05-01

Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled "Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program" is attached as supplementary material. This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. © 2015 Diabetes Technology Society.

Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Trial Calculation. Work Plan

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

Grabaskas, David; Bucknor, Matthew; Jerden, James

2016-02-01

The overall objective of the SFR Regulatory Technology Development Plan (RTDP) effort is to identify and address potential impediments to the SFR regulatory licensing process. In FY14, an analysis by Argonne identified the development of an SFR-specific MST methodology as an existing licensing gap with high regulatory importance and a potentially long lead-time to closure. This work was followed by an initial examination of the current state-of-knowledge regarding SFR source term development (ANLART-3), which reported several potential gaps. Among these were the potential inadequacies of current computational tools to properly model and assess the transport and retention of radionuclides duringmore » a metal fuel pool-type SFR core damage incident. The objective of the current work is to determine the adequacy of existing computational tools, and the associated knowledge database, for the calculation of an SFR MST. To accomplish this task, a trial MST calculation will be performed using available computational tools to establish their limitations with regard to relevant radionuclide release/retention/transport phenomena. The application of existing modeling tools will provide a definitive test to assess their suitability for an SFR MST calculation, while also identifying potential gaps in the current knowledge base and providing insight into open issues regarding regulatory criteria/requirements. The findings of this analysis will assist in determining future research and development needs.« less

Design and implementation of an audit trail in compliance with US regulations.

PubMed

Jiang, Keyuan; Cao, Xiang

2011-10-01

Audit trails have been used widely to ensure quality of study data and have been implemented in computerized clinical trials data systems. Increasingly, there is a need to audit access to study participant identifiable information to provide assurance that study participant privacy is protected and confidentiality is maintained. In the United States, several federal regulations specify how the audit trail function should be implemented. To describe the development and implementation of a comprehensive audit trail system that meets the regulatory requirements of assuring data quality and integrity and protecting participant privacy and that is also easy to implement and maintain. The audit trail system was designed and developed after we examined regulatory requirements, data access methods, prevailing application architecture, and good security practices. Our comprehensive audit trail system was developed and implemented at the database level using a commercially available database management software product. It captures both data access and data changes with the correct user identifier. Documentation of access is initiated automatically in response to either data retrieval or data change at the database level. Currently, our system has been implemented only on one commercial database management system. Although our audit trail algorithm does not allow for logging aggregate operations, aggregation does not reveal sensitive private participant information. Careful consideration must be given to data items selected for monitoring because selection of all data items using our system can dramatically increase the requirements for computer disk space. Evaluating the criticality and sensitivity of individual data items selected can control the storage requirements for clinical trial audit trail records. Our audit trail system is capable of logging data access and data change operations to satisfy regulatory requirements. Our approach is applicable to virtually any data that can be stored in a relational database.

47 CFR 101.1309 - Regulatory status.

Code of Federal Regulations, 2010 CFR

2010-10-01

... party may challenge the regulatory status granted an MAS licensee. System License Requirements ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Regulatory status. 101.1309 Section 101.1309... SERVICES Multiple Address Systems General Provisions § 101.1309 Regulatory status. (a) The Commission will...

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 occurrences of data integrity problems. © PDA, Inc. 2015.

Targeting Interferon Regulatory Factor for Cardiometabolic Diseases: Opportunities and Challenges.

PubMed

Zhang, Yaxing; Zhang, Xiao-Jing; Li, Hongliang

2017-01-01

The pathological activation of innate immune system may contribute to the development of cardiometabolic diseases. The interferon regulatory factor (IRF) family members, which are the major transcription factors in innate immune signaling, are implicated in cardiometabolic diseases. The aim of this review is to summary the current knowledge of the biological functions of IRFs in innate immune responses and immune cell development, and highlight our contemporary understanding of the functions and molecular mechanisms of IRFs in metabolic diseases, cardiovascular remodeling, and stroke. IRFs are the essential regulators of cardiometabolic diseases via immune-dependent and - independent manners. IRFs signaling is the promising target to manage the initiation and progression of cardiometabolic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

National Strategy for Modernizing the Regulatory System for Biotechnology Products

EPA Pesticide Factsheets

This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

Inference of Gene Regulatory Networks Incorporating Multi-Source Biological Knowledge via a State Space Model with L1 Regularization

PubMed Central

Hasegawa, Takanori; Yamaguchi, Rui; Nagasaki, Masao; Miyano, Satoru; Imoto, Seiya

2014-01-01

Comprehensive understanding of gene regulatory networks (GRNs) is a major challenge in the field of systems biology. Currently, there are two main approaches in GRN analysis using time-course observation data, namely an ordinary differential equation (ODE)-based approach and a statistical model-based approach. The ODE-based approach can generate complex dynamics of GRNs according to biologically validated nonlinear models. However, it cannot be applied to ten or more genes to simultaneously estimate system dynamics and regulatory relationships due to the computational difficulties. The statistical model-based approach uses highly abstract models to simply describe biological systems and to infer relationships among several hundreds of genes from the data. However, the high abstraction generates false regulations that are not permitted biologically. Thus, when dealing with several tens of genes of which the relationships are partially known, a method that can infer regulatory relationships based on a model with low abstraction and that can emulate the dynamics of ODE-based models while incorporating prior knowledge is urgently required. To accomplish this, we propose a method for inference of GRNs using a state space representation of a vector auto-regressive (VAR) model with L1 regularization. This method can estimate the dynamic behavior of genes based on linear time-series modeling constructed from an ODE-based model and can infer the regulatory structure among several tens of genes maximizing prediction ability for the observational data. Furthermore, the method is capable of incorporating various types of existing biological knowledge, e.g., drug kinetics and literature-recorded pathways. The effectiveness of the proposed method is shown through a comparison of simulation studies with several previous methods. For an application example, we evaluated mRNA expression profiles over time upon corticosteroid stimulation in rats, thus incorporating corticosteroid kinetics/dynamics, literature-recorded pathways and transcription factor (TF) information. PMID:25162401

Our Fat Future: Translating Adipose Stem Cell Therapy.

PubMed

Nordberg, Rachel C; Loboa, Elizabeth G

2015-09-01

Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. ©AlphaMed Press.

Drug safety: withdrawn medications are only part of the picture.

PubMed

Rawson, Nigel S B

2016-02-13

In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

TRACTOR_DB: a database of regulatory networks in gamma-proteobacterial genomes

PubMed Central

González, Abel D.; Espinosa, Vladimir; Vasconcelos, Ana T.; Pérez-Rueda, Ernesto; Collado-Vides, Julio

2005-01-01

Experimental data on the Escherichia coli transcriptional regulatory system has been used in the past years to predict new regulatory elements (promoters, transcription factors (TFs), TFs' binding sites and operons) within its genome. As more genomes of gamma-proteobacteria are being sequenced, the prediction of these elements in a growing number of organisms has become more feasible, as a step towards the study of how different bacteria respond to environmental changes at the level of transcriptional regulation. In this work, we present TRACTOR_DB (TRAnscription FaCTORs' predicted binding sites in prokaryotic genomes), a relational database that contains computational predictions of new members of 74 regulons in 17 gamma-proteobacterial genomes. For these predictions we used a comparative genomics approach regarding which several proof-of-principle articles for large regulons have been published. TRACTOR_DB may be currently accessed at http://www.bioinfo.cu/Tractor_DB, http://www.tractor.lncc.br/ or at http://www.cifn.unam.mx/Computational_Genomics/tractorDB. Contact Email id is tractor@cifn.unam.mx. PMID:15608293

The accession countries benefit in the field of plant protection products.

PubMed

Stanek, A

2004-04-01

Ten candidate countries are expected to join EU in 2004. In the field of plant protection product (PPP) regulation, at EU level, acceding states will have roles in evaluation for listing of active substances in Annex I of Directive 91/414/EEC and ensuring that at national level, regulatory procedures comply with the acquis communautaire. This paper briefly outlines the impact of the acquis on the roles of Member States at both EU and national levels. It then briefly explains the current Czech Republic regulatory system as operated by the State Phytosanitary Administration and the National Institute of Public Health and the steps that the Czech Republic will have to take to implement the acquis requirements. Finally it makes an assessment as to how successful implementation of the acquis will prove beneficial to the acceding states and the parties which rely on the service that the regulatory authorities provide (i.e. the public, farmers and growers and the agrochemical industry).

Markov State Models of gene regulatory networks.

PubMed

Chu, Brian K; Tse, Margaret J; Sato, Royce R; Read, Elizabeth L

2017-02-06

Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models. Application of transition path theory to the constructed Markov State Model decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching. In this proof-of-concept study, we found that the Markov State Model provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that this framework-adopted from the field of atomistic Molecular Dynamics-can be a useful tool for quantitative Systems Biology at the network scale.

Bioengineering and Coordination of Regulatory Networks and Intracellular Complexes to Maximize Hydrogen Production by Phototrophic Microorganisms

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

Tabita, F. Robert

2013-07-30

In this study, the Principal Investigator, F.R. Tabita has teamed up with J. C. Liao from UCLA. This project's main goal is to manipulate regulatory networks in phototrophic bacteria to affect and maximize the production of large amounts of hydrogen gas under conditions where wild-type organisms are constrained by inherent regulatory mechanisms from allowing this to occur. Unrestrained production of hydrogen has been achieved and this will allow for the potential utilization of waste materials as a feed stock to support hydrogen production. By further understanding the means by which regulatory networks interact, this study will seek to maximize themore » ability of currently available “unrestrained” organisms to produce hydrogen. The organisms to be utilized in this study, phototrophic microorganisms, in particular nonsulfur purple (NSP) bacteria, catalyze many significant processes including the assimilation of carbon dioxide into organic carbon, nitrogen fixation, sulfur oxidation, aromatic acid degradation, and hydrogen oxidation/evolution. Moreover, due to their great metabolic versatility, such organisms highly regulate these processes in the cell and since virtually all such capabilities are dispensable, excellent experimental systems to study aspects of molecular control and biochemistry/physiology are available.« less

Meeting the challenges of medical countermeasure development

PubMed Central

Maher, Carmen; Hu‐Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-01-01

Summary Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three‐pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures – and the systems to deliver them – and the requisite support of all stakeholders, including national leadership. PMID:22925432

SEURAT: Safety Evaluation Ultimately Replacing Animal Testing--recommendations for future research in the field of predictive toxicology.

PubMed

Daston, George; Knight, Derek J; Schwarz, Michael; Gocht, Tilman; Thomas, Russell S; Mahony, Catherine; Whelan, Maurice

2015-01-01

The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.

Interplay between cardiac transcription factors and non-coding RNAs in predisposing to atrial fibrillation.

PubMed

Mikhailov, Alexander T; Torrado, Mario

2018-05-12

There is growing evidence that putative gene regulatory networks including cardio-enriched transcription factors, such as PITX2, TBX5, ZFHX3, and SHOX2, and their effector/target genes along with downstream non-coding RNAs can play a potentially important role in the process of adaptive and maladaptive atrial rhythm remodeling. In turn, expression of atrial fibrillation-associated transcription factors is under the control of upstream regulatory non-coding RNAs. This review broadly explores gene regulatory mechanisms associated with susceptibility to atrial fibrillation-with key examples from both animal models and patients-within the context of both cardiac transcription factors and non-coding RNAs. These two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective control of atrial rhythm effector gene expression. Perturbations of a dynamic expression balance between transcription factors and corresponding non-coding RNAs can provoke the development or promote the progression of atrial fibrillation. We also outline deficiencies in current models and discuss ongoing studies to clarify remaining mechanistic questions. An understanding of the function of transcription factors and non-coding RNAs in gene regulatory networks associated with atrial fibrillation risk will enable the development of innovative therapeutic strategies.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

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

Self-Regulation across Time of First-Generation Online Learners

ERIC Educational Resources Information Center

Barnard-Brak, Lucy; Paton, Valerie Osland; Lan, William Y.

2010-01-01

Self-regulatory skills have been associated with positive outcomes for learners. In the current study, we examined the self-regulatory skills of students who are first-generation online learners over the course of their first semester of online instruction. The purpose of this study is to determine whether the online self-regulatory skills of…

17 CFR 400.4 - Information concerning associated persons of financial institutions that are government...

Code of Federal Regulations, 2010 CFR

2010-04-01

... completed and current Form U-4 (promulgated by a self-regulatory organization) or Form MSD-4 (as required... regulatory agency for such financial institution, a statement correcting such information. (c) For the... shall: (1) Promptly obtain and, within 10 days thereafter, file with the appropriate regulatory agency...

77 FR 52977 - Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule; Market Risk Capital Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... Corporation 12 CFR Parts 324, 325 Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule... 325 RIN 3064-AD97 Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule; Market Risk... the agencies' current capital rules. In this NPR (Advanced Approaches and Market Risk NPR) the...

78 FR 27113 - Generic Drug User Fee Amendments of 2012; Regulatory Science Initiatives Public Hearing; Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

.... FDA-2013-N-0402] Generic Drug User Fee Amendments of 2012; Regulatory Science Initiatives Public... public meeting that will provide an overview of the current status of the regulatory science initiatives... societies, and other interested stakeholders-- as it fulfills its statutory requirement under the Generic...

Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential.

PubMed

Spitz, Charlotte; Winkels, Holger; Bürger, Christina; Weber, Christian; Lutgens, Esther; Hansson, Göran K; Gerdes, Norbert

2016-03-01

Atherosclerosis is a chronic inflammatory disease that is mediated by innate and adaptive immune responses. The disease is characterized by sub-endothelial accumulation and modification of lipids in the artery wall triggering an inflammatory reaction which promotes lesion progression and eventual plaque rupture, thrombus formation, and the respective clinical sequelae such as myocardial infarction or stroke. During the past decade, T-cell-mediated immune responses, especially control of pro-inflammatory signals by regulatory T cells (Tregs), have increasingly attracted the interest of experimental and clinical researchers. By suppression of T cell proliferation and secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-β, Tregs exert their atheroprotective properties. Atherosclerosis-prone, hyperlipidemic mice harbor systemically less Tregs compared to wild-type mice, suggesting an imbalance of immune cells which affects local and systemic inflammatory and potentially metabolic processes leading to atherogenesis. Restoring or increasing Treg frequency and enhancing their suppressive capacity by various modulations may pose a promising approach for treating inflammatory conditions such as cardiovascular diseases. In this review, we briefly summarize the immunological basics of atherosclerosis and introduce the role and contribution of different subsets of T cells. We then discuss experimental data and current knowledge pertaining to Tregs in atherosclerosis and perspectives on manipulating the adaptive immune system to alleviate atherosclerosis and cardiovascular disease.

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

PubMed Central

Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

2013-01-01

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

Regulatory considerations on new adjuvants and delivery systems.

PubMed

Sesardic, D

2006-04-12

New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

76 FR 76777 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

... fees: (i) For a data set of real-time TRACE disseminated TBA transaction data at the same rates currently in effect for similar real-time TRACE disseminated data sets, and (ii) for a data set of historic TRACE TBA transaction data at the same rates currently in effect for similar Historic TRACE Data sets.\\4...

75 FR 2897 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... of a mutual fund to investors at the fund's current net asset value, plus any applicable sales load... codified as NASD IM-2830-2, that requires members to sell mutual funds at the public offering price not... sell shares of mutual funds to non-member broker-dealers at a price below the current public offering...

77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

...The Office of the Comptroller of the Currency (OCC), Board of Governors of the Federal Reserve System (Board), and the Federal Deposit Insurance Corporation (FDIC) (collectively, the agencies) are seeking comment on three Notices of Proposed Rulemaking (NPR) that would revise and replace the agencies' current capital rules. In this NPR, the agencies are proposing to revise their risk-based and leverage capital requirements consistent with agreements reached by the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for More Resilient Banks and Banking Systems'' (Basel III). The proposed revisions would include implementation of a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for banking organizations subject to the advanced approaches capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator measure. Additionally, consistent with Basel III, the agencies are proposing to apply limits on a banking organization's capital distributions and certain discretionary bonus payments if the banking organization does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk- based capital requirements. This NPR also would establish more conservative standards for including an instrument in regulatory capital. As discussed in the proposal, the revisions set forth in this NPR are consistent with section 171 of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act), which requires the agencies to establish minimum risk-based and leverage capital requirements. In connection with the proposed changes to the agencies' capital rules in this NPR, the agencies are also seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related NPRs are discussed further in the SUPPLEMENTARY INFORMATION.

Deciphering RNA regulatory elements in trypanosomatids: one piece at a time or genome-wide?

PubMed

Gazestani, Vahid H; Lu, Zhiquan; Salavati, Reza

2014-05-01

Morphological and metabolic changes in the life cycle of Trypanosoma brucei are accomplished by precise regulation of hundreds of genes. In the absence of transcriptional control, RNA-binding proteins (RBPs) shape the structure of gene regulatory maps in this organism, but our knowledge about their target RNAs, binding sites, and mechanisms of action is far from complete. Although recent technological advances have revolutionized the RBP-based approaches, the main framework for the RNA regulatory element (RRE)-based approaches has not changed over the last two decades in T. brucei. In this Opinion, after highlighting the current challenges in RRE inference, we explain some genome-wide solutions that can significantly boost our current understanding about gene regulatory networks in T. brucei. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cardiac mitochondrial matrix and respiratory complex protein phosphorylation

PubMed Central

Covian, Raul

2012-01-01

It has become appreciated over the last several years that protein phosphorylation within the cardiac mitochondrial matrix and respiratory complexes is extensive. Given the importance of oxidative phosphorylation and the balance of energy metabolism in the heart, the potential regulatory effect of these classical signaling events on mitochondrial function is of interest. However, the functional impact of protein phosphorylation and the kinase/phosphatase system responsible for it are relatively unknown. Exceptions include the well-characterized pyruvate dehydrogenase and branched chain α-ketoacid dehydrogenase regulatory system. The first task of this review is to update the current status of protein phosphorylation detection primarily in the matrix and evaluate evidence linking these events with enzymatic function or protein processing. To manage the scope of this effort, we have focused on the pathways involved in energy metabolism. The high sensitivity of modern methods of detecting protein phosphorylation and the low specificity of many kinases suggests that detection of protein phosphorylation sites without information on the mole fraction of phosphorylation is difficult to interpret, especially in metabolic enzymes, and is likely irrelevant to function. However, several systems including protein translocation, adenine nucleotide translocase, cytochrome c, and complex IV protein phosphorylation have been well correlated with enzymatic function along with the classical dehydrogenase systems. The second task is to review the current understanding of the kinase/phosphatase system within the matrix. Though it is clear that protein phosphorylation occurs within the matrix, based on 32P incorporation and quantitative mass spectrometry measures, the kinase/phosphatase system responsible for this process is ill-defined. An argument is presented that remnants of the much more labile bacterial protein phosphoryl transfer system may be present in the matrix and that the evaluation of this possibility will require the application of approaches developed for bacterial cell signaling to the mitochondria. PMID:22886415

[Research of RAAS: progress and perspective].

PubMed

Akazawa, Hiroshi; Komuro, Issei

2012-09-01

Pharmacological inhibitions of the renin-angiotensin-aldosterone system (RAAS) are crowned with one of the greatest success in the current field of cardiovascular medicine. In addition to the systemic effects including elevation of blood pressure and retention of sodium and water, sustained and excessive RAAS activation has direct and deleterious effects on a wide variety of tissues. Recent studies have deciphered the regulatory mechanisms underlying tissue RAAS activation at cellular and molecular levels, and suggested pathogenic roles of RAAS activation in hitherto unanticipated disorders such as muscular dystrophy, osteoporosis, cancer, and aging itself. Novel drugs targeting RAAS are under research and development in search for further efficacy, specificity, and even multifunctionality. This review will discuss the current progress and future perspective of RAAS research.

3D printing applications for transdermal drug delivery.

PubMed

Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

2018-06-15

The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Climate change adaptation in regulated water utilities

NASA Astrophysics Data System (ADS)

Vicuna, S.; Melo, O.; Harou, J. J.; Characklis, G. W.; Ricalde, I.

2017-12-01

Concern about climate change impacts on water supply systems has grown in recent years. However, there are still few examples of pro-active interventions (e.g. infrastructure investment or policy changes) meant to address plausible future changes. Deep uncertainty associated with climate impacts, future demands, and regulatory constraints might explain why utility planning in a range of contexts doesn't explicitly consider climate change scenarios and potential adaptive responses. Given the importance of water supplies for economic development and the cost and longevity of many water infrastructure investments, large urban water supply systems could suffer from lack of pro-active climate change adaptation. Water utilities need to balance the potential for high regret stranded assets on the one side, with insufficient supplies leading to potentially severe socio-economic, political and environmental failures on the other, and need to deal with a range of interests and constraints. This work presents initial findings from a project looking at how cities in Chile, the US and the UK are developing regulatory frameworks that incorporate utility planning under uncertainty. Considering for example the city of Santiago, Chile, recent studies have shown that although high scarcity cost scenarios are plausible, pre-emptive investment to guard from possible water supply failures is still remote and not accommodated by current planning practice. A first goal of the project is to compare and contrast regulatory approaches to utility risks considering climate change adaptation measures. Subsequently we plan to develop and propose a custom approach for the city of Santiago based on lessons learned from other contexts. The methodological approach combines institutional assessment of water supply regulatory frameworks with simulation-based decision-making under uncertainty approaches. Here we present initial work comparing the regulatory frameworks in Chile, UK and USA evaluating their ability to incorporate uncertain climate and other changes into long-term infrastructure investment planning. The potential for regulatory and financial adaptive measures is explored in addition to a discussion on evaluating their appropriateness via various modelling-based intervention decision-making approaches.

Towards systems metabolic engineering of microorganisms for amino acid production.

PubMed

Park, Jin Hwan; Lee, Sang Yup

2008-10-01

Microorganisms capable of efficient production of amino acids have traditionally been developed by random mutation and selection method, which might cause unwanted physiological changes in cellular metabolism. Rational genome-wide metabolic engineering based on systems and synthetic biology tools, which is termed 'systems metabolic engineering', is rising as an alternative to overcome these problems. Recently, several amino acid producers have been successfully developed by systems metabolic engineering, where the metabolic engineering procedures were performed within a systems biology framework, and entire metabolic networks, including complex regulatory circuits, were engineered in an integrated manner. Here we review the current status of systems metabolic engineering successfully applied for developing amino acid producing strains and discuss future prospects.

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

PubMed

Cortese-Krott, Miriam M; Koning, Anne; Kuhnle, Gunter G C; Nagy, Peter; Bianco, Christopher L; Pasch, Andreas; Wink, David A; Fukuto, Jon M; Jackson, Alan A; van Goor, Harry; Olson, Kenneth R; Feelisch, Martin

2017-10-01

Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

The US health care system: Part 1: Our current system.

PubMed

Nuwer, M R; Esper, G J; Donofrio, P D; Szaflarski, J P; Barkley, G L; Swift, T R

2008-12-02

The US health care crisis is of great concern to American neurologists. The United States has the world's most expensive health care system yet one-sixth of Americans are uninsured. The cost and volume of procedures is expanding, while reimbursement for office visits is declining. Pharmaceutical costs, durable goods, and home health care are growing disproportionately to other services. Carriers spend more for their own administration and profit than on payments to physicians. This first article on the US health care system identifies problems and proposes solutions, many of which are championed by the American Academy of Neurology through its legislative and regulatory committees.

Regulatory Fit Improves Fitness for People With Low Exercise Experience.

PubMed

Kay, Sophie A; Grimm, Lisa R

2017-04-01

Considering only 20.8% of American adults meet current physical activity recommendations, it is important to examine the psychological processes that affect exercise motivation and behavior. Drawing from regulatory fit theory, this study examined how manipulating regulatory focus and reward structures would affect exercise performance, with a specific interest in investigating whether exercise experience would moderate regulatory fit effects. We predicted that regulatory fit effects would appear only for participants with low exercise experience. One hundred and sixty-five young adults completed strength training exercise tasks (i.e., sit-ups, squats, plank, and wall-sit) in regulatory match or mismatch conditions. Consistent with predictions, only participants low in experience in regulatory match conditions exercised more compared with those in regulatory mismatch conditions. Although this is the first study manipulating regulatory fit in a controlled setting to examine exercise behavior, findings suggest that generating regulatory fit could positively influence those low in exercise experience.

A Golden Ticket to Future Occupational and Environmental Health Monitoring

DTIC Science & Technology

2015-10-01

by the BE career field, an assessment of the regulatory monitoring requirements and current detection capabilities was critical . The next step in...research criteria due to the inability to predict the cost of production for these detection systems. Until a standardization of mass scale production...the health risk assessment process and is critical to keeping the base population safe from occupational and environmental exposures. The predominant

76 FR 69308 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

... Options, and 1082, Firm Quotations, to extend, through February 29, 2012, a pilot program (the ``pilot... 1082(a)(ii)(B)(3). Rather than immediately executing at the next available price, the PHLX XL system.... Currently, Exchange Rules 1082(a)(ii)(B)(3)(g)(iv)(A)(3), 1082(a)(ii)(B)(3)(g)(iv)(A)(4), 1082(a)(ii)(B)(3...

76 FR 13678 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

..., Openings in Options, and 1082, Firm Quotations, to extend, through July 31, 2011, a pilot program (the... 1082(a)(ii)(B)(3). Rather than immediately executing at the next available price, the PHLX XL system.... Currently, Exchange Rules 1082(a)(ii)(B)(3)(g)(iv)(A)(3), 1082(a)(ii)(B)(3)(g)(iv)(A)(4), 1082(a)(ii)(B)(3...

Case Study: South Texas Veterans Health Care System’s Communication Center

DTIC Science & Technology

2008-07-14

appropriate access to health care; technical quality is providing world-class care to our veterans; customer satisfaction is ensuring the STVHCS patients and...were not called. These results not only improved access to health care, but also positively affected customer service. 111 Case Study: South Texas...increased waiting times for the patient . With current regulatory requirements calling for improved access to health care services, many hospital and

76 FR 32255 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

... book were $10.00 x $10.05, and a market participant entered a Post-Only Order to buy at $10.05, the.... Thus, if a sell order is on the book at $10 and a Post-Only Order to buy at $10.01 is entered, the... order's current behavior when crossing an existing order on the System. PHLX also notes that NASDAQ has...

Current Regulations and Regulatory Actions

EPA Pesticide Factsheets

This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

Online Self-Regulatory Learning Behaviors as a Mediator in the Relationship between Online Course Perceptions with Achievement

ERIC Educational Resources Information Center

Barnard, Lucy; Paton, Valerie; Lan, William

2008-01-01

Positive perceptions of online course communication and collaboration have been associated with better academic outcomes, while self-regulatory learning behaviors have also been linked to academic achievement and other positive learning outcomes. In the current study, we examined whether self-regulatory learning behaviors may be considered as…

Meta-Analysis of Single-Case Design Research on Self-Regulatory Interventions for Academic Performance

ERIC Educational Resources Information Center

Perry, Valerie; Albeg, Loren; Tung, Catherine

2012-01-01

The current study examined the effects of self-regulatory interventions on reading, writing, and math by conducting a meta-analysis of single-case design research. Self-regulatory interventions have promise as an effective approach that is both minimally invasive and involves minimal resources. Effects of the interventions were analyzed by…

Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment.

PubMed

Abou-El-Enein, Mohamed; Cathomen, Toni; Ivics, Zoltán; June, Carl H; Renner, Matthias; Schneider, Christian K; Bauer, Gerhard

2017-10-05

As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues. Copyright © 2017 Elsevier Inc. All rights reserved.

The pedestrian watchmaker: Genetic clocks from engineered oscillators

PubMed Central

Cookson, Natalie A.; Tsimring, Lev S.; Hasty, Jeff

2010-01-01

The crucial role of time-keeping has required organisms to develop sophisticated regulatory networks to ensure the reliable propagation of periodic behavior. These biological clocks have long been a focus of research; however, a clear understanding of how they maintain oscillations in the face of unpredictable environments and the inherent noise of biological systems remains elusive. Here, we review the current understanding of circadian oscillations using Drosophila melanogaster as a typical example and discuss the utility of an alternative synthetic biology approach to studying these highly intricate systems. PMID:19903483

Children, Families, and Disparities: Pediatric Provisions in the Affordable Care Act.

PubMed

Grace, Aimee M; Horn, Ivor; Hall, Robert; Cheng, Tina L

2015-10-01

The Affordable Care Act has caused and continues to cause sweeping changes throughout the health system in the United States. Poorly explained, complex, controversial, confusing, and subject to continuous legal and regulatory definition, the law stands as a hallmark piece of legislation that will change the health sector in America forever. This article summarizes the Affordable Care Act with a focus on children, families, and disparities. Also provided is the context of the current system of health care coverage in the United States. Published by Elsevier Inc.

[To the issue on the optimization and regulation of microclimate in the subway trains and stations].

PubMed

Leksin, A G; Beresneva, T G; Kaptsov, V A; Korotich, L P; Evlampieva, M N; Timoshenkova, E V

2014-01-01

There is presented an overview of currently existing regulatory framework governing the parameters of the microclimate in the salons of subway passenger cars and stations. Analysis of the normative documents indicated that they contain very incomplete, contradictory, often unfounded information about the parameters of microclimate parameters in salons of subway rolling stock. Also, there are no clear cut hygienically-sound requirements for the work of imposed on the rolling stock subway systems provide microclimate, including new systems for air conditioning and disinfection.

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.

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.

Feedback from the European Bioanalysis Forum: focus workshop on current analysis of immunogenicity: best practices and regulatory hurdles.

PubMed

Goodman, Joanne; Cowen, Simon; Devanarayan, Viswanath; Egging, David; Emrich, Thomas; Golob, Michaela; Kramer, Daniel; McNally, Jim; Munday, James; Nelson, Robert; Pedras-Vasconcelos, João A; Piironen, Timo; Sickert, Denise; Skibeli, Venke; Fjording, Marianne Scheel; Timmerman, Philip

2018-02-01

European Bioanalysis Forum Workshop, Lisbon, Portugal, September 2016: At the recent European Bioanalysis Forum Focus Workshop, 'current analysis of immunogenicity: best practices and regulatory hurdles', several important challenges facing the bioanalytical community in relation to immunogenicity assays were discussed through a mixture of presentations and panel sessions. The main areas of focus were the evolving regulatory landscape, challenges of assay interferences from either drug or target, cut-point setting and whether alternative assays can be used to replace neutralizing antibody assays. This workshop report captures discussions and potential solutions and/or recommendations made by the speakers and delegates.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

Biosimilar Products in the Modern U.S. Health Care and Regulatory Landscape.

PubMed

Peterson, Jesse; Budlong, Holly; Affeldt, Tim; Skiermont, Kyle; Kyllo, Gregg; Heaton, Al

2017-12-01

Biosimilars have the potential to greatly reduce medication costs in the United States. As of July 1, 2017, 5 biosimilars have been approved by the FDA, but only 2 are available for purchase. This commentary outlines the efforts of an integrated health system to ensure biosimilar accessibility and discusses the current challenges and future implications. We highlight the implementation of a health plan policy and how a health system's formulary committee can encourage use while considering provider perceptions and operational challenges. In addition, we provide our perspective on potential implications for pricing, site of care, and pharmacy dispensing practices based on our experience with regulatory hurdles and market trends. Overall, we believe biosimilars are a good thing for the health care system, but their expected benefit may not be realized for years to come. No outside funding supported this work. Affeldt reports advisory board membership with Janssen, and Skiermont reports membership with Amgen and McKesson. The other authors have nothing to disclose. Peterson and Budlong contributed the study concept and design and wrote the manuscript. Affeldt, Skiermont, Kyllo, and Heaton reviewed and revised the manuscript.

Unmanned aerial systems for photogrammetry and remote sensing: A review

NASA Astrophysics Data System (ADS)

Colomina, I.; Molina, P.

2014-06-01

We discuss the evolution and state-of-the-art of the use of Unmanned Aerial Systems (UAS) in the field of Photogrammetry and Remote Sensing (PaRS). UAS, Remotely-Piloted Aerial Systems, Unmanned Aerial Vehicles or simply, drones are a hot topic comprising a diverse array of aspects including technology, privacy rights, safety and regulations, and even war and peace. Modern photogrammetry and remote sensing identified the potential of UAS-sourced imagery more than thirty years ago. In the last five years, these two sister disciplines have developed technology and methods that challenge the current aeronautical regulatory framework and their own traditional acquisition and processing methods. Navety and ingenuity have combined off-the-shelf, low-cost equipment with sophisticated computer vision, robotics and geomatic engineering. The results are cm-level resolution and accuracy products that can be generated even with cameras costing a few-hundred euros. In this review article, following a brief historic background and regulatory status analysis, we review the recent unmanned aircraft, sensing, navigation, orientation and general data processing developments for UAS photogrammetry and remote sensing with emphasis on the nano-micro-mini UAS segment.

Neutral forces acting on intragenomic variability shape the Escherichia coli regulatory network topology.

PubMed

Ruths, Troy; Nakhleh, Luay

2013-05-07

Cis-regulatory networks (CRNs) play a central role in cellular decision making. Like every other biological system, CRNs undergo evolution, which shapes their properties by a combination of adaptive and nonadaptive evolutionary forces. Teasing apart these forces is an important step toward functional analyses of the different components of CRNs, designing regulatory perturbation experiments, and constructing synthetic networks. Although tests of neutrality and selection based on molecular sequence data exist, no such tests are currently available based on CRNs. In this work, we present a unique genotype model of CRNs that is grounded in a genomic context and demonstrate its use in identifying portions of the CRN with properties explainable by neutral evolutionary forces at the system, subsystem, and operon levels. We leverage our model against experimentally derived data from Escherichia coli. The results of this analysis show statistically significant and substantial neutral trends in properties previously identified as adaptive in origin--degree distribution, clustering coefficient, and motifs--within the E. coli CRN. Our model captures the tightly coupled genome-interactome of an organism and enables analyses of how evolutionary events acting at the genome level, such as mutation, and at the population level, such as genetic drift, give rise to neutral patterns that we can quantify in CRNs.

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Code of Federal Regulations, 2010 CFR

2010-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... (CONTINUED) FORMS, SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot...

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Code of Federal Regulations, 2011 CFR

2011-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... (CONTINUED) FORMS, SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot...

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Code of Federal Regulations, 2013 CFR

2013-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... (CONTINUED) FORMS, SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot...

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Code of Federal Regulations, 2012 CFR

2012-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... (CONTINUED) FORMS, SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot...

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Code of Federal Regulations, 2014 CFR

2014-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... (CONTINUED) FORMS, SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot...

Plant systems biology: network matters.

PubMed

Lucas, Mikaël; Laplaze, Laurent; Bennett, Malcolm J

2011-04-01

Systems biology is all about networks. A recent trend has been to associate systems biology exclusively with the study of gene regulatory or protein-interaction networks. However, systems biology approaches can be applied at many other scales, from the subatomic to the ecosystem scales. In this review, we describe studies at the sub-cellular, tissue, whole plant and crop scales and highlight how these studies can be related to systems biology. We discuss the properties of system approaches at each scale as well as their current limits, and pinpoint in each case advances unique to the considered scale but representing potential for the other scales. We conclude by examining plant models bridging different scales and considering the future prospects of plant systems biology. © 2011 Blackwell Publishing Ltd.

Shaping nursing profession regulation through history - a systematic review.

PubMed

Stievano, A; Caruso, R; Pittella, F; Shaffer, F A; Rocco, G; Fairman, J

2018-03-23

The aim of this systematic review was to provide a critical synthesis of the factors that historically shaped the advancements of nursing regulators worldwide. An in-depth examination of the different factors that moulded regulatory changes over time is pivotal to comprehend current issues in nursing. In the light of global health scenarios, the researchers explored the factors that historically influenced the socio-contextual circumstances upon which governments made regulatory changes. A systematic search was performed on the following databases: PubMed, CINAHL, Scopus, OpenGrey and ScienceDirect. The review included papers from January 2000 to October 2016 published in English. The authors used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and an inductive thematic approach for synthesis. Two main themes were identified: factors underpinning current challenges and historical and contextual triggers of regulation. The first theme was composed of three aspects: education, migration and internationalization, and policy and regulation; the second theme consisted of four attributes: demographics, economics, history of registration and wars, and historical changes in nursing practice. Factors that shaped nursing regulation were linked to changing demographics and economics, education, history of nursing registration, shifting patterns of migration and internationalization, nursing practice, policy and regulation and significant societal turns often prompted by wars. A deeper understanding of the developments of the nursing regulatory institutions provides the foundation for portable standards that can be applied across an array of jurisdictions to guarantee a better public safety. Understanding factors that socially, legislatively and politically have influenced the development of regulatory bodies over time helps to mould local, national and international policies that have a stronger impact on health worldwide. To achieve this, there must be effective cooperation among systems of nursing regulations globally. © 2018 International Council of Nurses.

In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.

PubMed

Lennernäs, H; Lindahl, A; Van Peer, A; Ollier, C; Flanagan, T; Lionberger, R; Nordmark, A; Yamashita, S; Yu, L; Amidon, G L; Fischer, V; Sjögren, E; Zane, P; McAllister, M; Abrahamsson, B

2017-04-03

The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia.

PubMed

Gogarty, B

2003-04-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001.

Land Development and Subdivision Regulations that Support Access Management

DOT National Transportation Integrated Search

1993-01-01

This report examines the role of the comprehensive plan in developing an access : management program, aspects of current regulatory practice that contribute to : access problems, and regulatory techniques that support access management : principles. ...

Insights into nuclear dynamics using live-cell imaging approaches.

PubMed

Bigley, Rachel B; Payumo, Alexander Y; Alexander, Jeffrey M; Huang, Guo N

2017-03-01

The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems. Live-cell imaging approaches are capable of providing quantitative assessment of the dynamics of gene regulatory interactions within the nucleus. We survey recent insights into what live-cell imaging approaches have provided the field of nuclear dynamics. In this review, we focus on interactions of DNA with other DNA loci, proteins, RNA, and the nuclear envelope. WIREs Syst Biol Med 2017, 9:e1372. doi: 10.1002/wsbm.1372 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Colorado Water Watch: real-time groundwater monitoring for possible contamination from oil and gas activities.

PubMed

Son, Ji-Hee; Hanif, Asma; Dhanasekar, Ashwin; Carlson, Kenneth H

2018-02-13

Currently, only a few states in the USA (e.g., Colorado and Ohio) require mandatory baseline groundwater sampling from nearby groundwater wells prior to drilling a new oil or gas well. Colorado is the first state to regulate groundwater testing before and after drilling, which requires one pre-drilling sample and two additional post-drilling samples within 6-12 months and 5-6 years of drilling. However, the monitoring method is limited to the state's regulatory agency and to ex situ sampling, which offers only a snapshot in time. To overcome the limitations and increase monitoring performance, a new groundwater monitoring system, Colorado Water Watch (CWW), was introduced as a decision-making tool to support the state's regulatory agency and also to provide real-time groundwater quality data to both the industry and the public. The CWW uses simple in situ water quality sensors based on the surrogate sensing technology that employs an event detection system to screen the incoming data in near real-time.

Validation of gamma irradiator controls for quality and regulatory compliance

NASA Astrophysics Data System (ADS)

Harding, Rorry B.; Pinteric, Francis J. A.

1995-09-01

Since 1978 the U.S. Food and Drug Administration (FDA) has had both the legal authority and the Current Good Manufacturing Practice (CGMP) regulations in place to require irradiator owners who process medical devices to produce evidence of Irradiation Process Validation. One of the key components of Irradiation Process Validation is the validation of the irradiator controls. However, it is only recently that FDA audits have focused on this component of the process validation. What is Irradiator Control System Validation? What constitutes evidence of control? How do owners obtain evidence? What is the irradiator supplier's role in validation? How does the ISO 9000 Quality Standard relate to the FDA's CGMP requirement for evidence of Control System Validation? This paper presents answers to these questions based on the recent experiences of Nordion's engineering and product management staff who have worked with several US-based irradiator owners. This topic — Validation of Irradiator Controls — is a significant regulatory compliance and operations issue within the irradiator suppliers' and users' community.

Medicine shortages: a commentary on causes and mitigation strategies.

PubMed

Iyengar, Swathi; Hedman, Lisa; Forte, Gilles; Hill, Suzanne

2016-09-29

Shortages of medicines and vaccines have been reported in countries of all income levels in recent years. Shortages can result from one or multiple causes, including shortages of raw materials, manufacturing capacity problems, industry consolidation, marketing practices, and procurement and supply chain management. Existing approaches to mitigate shortages include advance notice systems managed through medicine regulatory authorities, special programmes that track medicines, and interventions to improve efficiency of the medicine supply chain. Redistribution of supplies at the national level can mitigate some shortages in the short term. International redistribution and exceptional regulatory approvals may be used in limited circumstances, with the understanding that such approaches are complex and may introduce cost and quality risks. If it is necessary to prioritise patients to receive a medicine that is in shortage, evidence-based practice should be used to ensure optimal allocation. Important steps in reducing medicine shortages and their impact include identifying medicines that are most at risk, developing reporting systems to share information on current and emerging shortages, and improving data from medicine supply chains.

Bioattractors: dynamical systems theory and the evolution of regulatory processes

PubMed Central

Jaeger, Johannes; Monk, Nick

2014-01-01

In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype–phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait – such as attractors with associated basins and their bifurcations – define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. PMID:24882812

Upstream oversight assessment for agrifood nanotechnology: a case studies approach.

PubMed

Kuzma, Jennifer; Romanchek, James; Kokotovich, Adam

2008-08-01

Although nanotechnology is broadly receiving attention in public and academic circles, oversight issues associated with applications for agriculture and food remain largely unexplored. Agrifood nanotechnology is at a critical stage in which informed analysis can help shape funding priorities, risk assessment, and oversight activities. This analysis is designed to help society and policymakers anticipate and prepare for challenges posed by complicated, convergent applications of agrifood nanotechnology. The goal is to identify data, risk assessment, regulatory policy, and engagement needs for overseeing these products so they can be addressed prior to market entry. Our approach, termed upstream oversight assessment (UOA), has potential as a key element of anticipatory governance. It relies on distinct case studies of proposed applications of agrifood nanotechnology to highlight areas that need study and attention. As a tool for preparation, UOA anticipates the types and features of emerging applications; their endpoints of use in society; the extent to which users, workers, ecosystems, or consumers will be exposed; the nature of the material and its safety; whether and where the technologies might fit into current regulatory system(s); the strengths and weaknesses of the system(s) in light of these novel applications; and the possible social concerns related to oversight for them.

Food policy in the Canadian North: Is there a role for country food markets?

PubMed

Ford, James D; Macdonald, Joanna Petrasek; Huet, Catherine; Statham, Sara; MacRury, Allison

2016-03-01

Food insecurity is widely reported to be at a crisis level in the Inuit territory of Nunavut, Canada. Various policies, programs, and initiatives have been proposed to tackle the problem, with increasing interest in developing a system of country food markets (CFMs) similar to Greenland. We examine if CFMs offer a feasible, sustainable, and effective model for strengthening food systems in Nunavut, examining the model of Greenland and drawing on semi-structured interviews with key informants (n = 45). The Greenland experience indicates that CFMs can provide access to sufficient, safe, and nutritious food on a regular basis, and can diversify locally available foods. These benefits are transferable to Nunavut, although knowledge gaps, regulatory and institutional conditions, and concerns over how CFMs might affect the cultural basis of food systems, underlies apprehension over their development in the territory. We conclude that Nunavut is not currently in the position to develop CFMs, but the role of such markets in potentially strengthening food systems should not be discounted. Future development would need to solicit community input on CFMs, resolve regulatory issues around wildlife management and harvesting, and study how future risks would affect sustainability and effectiveness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methods for Analyzing the Benefits and Costs of Distributed Photovoltaic Generation to the U.S. Electric Utility System

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

Denholm, P.; Margolis, R.; Palmintier, B.

This report outlines the methods, data, and tools that could be used at different levels of sophistication and effort to estimate the benefits and costs of DGPV. In so doing, we identify the gaps in current benefit-cost-analysis methods, which we hope will inform the ongoing research agenda in this area. The focus of this report is primarily on benefits and costs from the utility or electricity generation system perspective. It is intended to provide useful background information to utility and regulatory decision makers and their staff, who are often being asked to use or evaluate estimates of the benefits andmore » cost of DGPV in regulatory proceedings. Understanding the technical rigor of the range of methods and how they might need to evolve as DGPV becomes a more significant contributor of energy to the electricity system will help them be better consumers of this type of information. This report is also intended to provide information to utilities, policy makers, PV technology developers, and other stakeholders, which might help them maximize the benefits and minimize the costs of integrating DGPV into a changing electricity system.« less

Underground storage tank management plan

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

NONE

1994-09-01

The Underground Storage Tank (UST) Management Program at the Oak Ridge Y-12 Plant was established to locate UST systems in operation at the facility, to ensure that all operating UST systems are free of leaks, and to establish a program for the removal of unnecessary UST systems and upgrade of UST systems that continue to be needed. The program implements an integrated approach to the management of UST systems, with each system evaluated against the same requirements and regulations. A common approach is employed, in accordance with Tennessee Department of Environment and Conservation (TDEC) regulations and guidance, when corrective actionmore » is mandated. This Management Plan outlines the compliance issues that must be addressed by the UST Management Program, reviews the current UST inventory and compliance approach, and presents the status and planned activities associated with each UST system. The UST Management Plan provides guidance for implementing TDEC regulations and guidelines for petroleum UST systems. (There are no underground radioactive waste UST systems located at Y-12.) The plan is divided into four major sections: (1) regulatory requirements, (2) implementation requirements, (3) Y-12 Plant UST Program inventory sites, and (4) UST waste management practices. These sections describe in detail the applicable regulatory drivers, the UST sites addressed under the Management Program, and the procedures and guidance used for compliance with applicable regulations.« less

Transdermal patches: history, development and pharmacology

PubMed Central

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Applicability of Unmanned Aerial Systems to Homeland Defense Missions

DTIC Science & Technology

2006-12-01

adopted many of the suggestion from the NAPA report. A significant milestone in the agency’s history occurred in 1996 when President Clinton extended...Surveillance and Civil Liberties”, in Information Ethics: Privacy and Intellectual Property, Lee Freeman and A. Graham Peace, Hershey , Pa, 2005. p.165. 164...of registry first. The second expectation is for aircraft to follow the “air 197 Mark Peterson , “The UAV and the Current and Future Regulatory

Preventing type 2 diabetes: Changing the food industry

PubMed Central

Popkin, Barry M.; Kenan, W. R.

2016-01-01

Improving our global diet by working with the food industry is a fairly complex task. Previously the global food manufacturing companies and governments were the major players. However, matters have shifted rapidly so that food retailers, food manufacturers, the restaurant–food service sector, and agribusinesses are now the major players. The current modern system of packaged processed food has now penetrated the globe—rich and poor, rural and urban are all in reach of this food system. Consequently, working with this complex sector when possible and an array of governmental regulatory large-scale options to improve our diet have increased in importance. Taxation of unhealthy foods and beverages, marketing controls, and front of the package labeling are the primary current options. Evaluations of the impacts of both public and industry initiatives are needed. PMID:27432072

75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... has proposed this rule change in order to preserve FINRA's current quorum requirements in anticipation.... Sec. 19 (2010). In anticipation of the foregoing amendment to the General Corporation Law, FINRA has...

Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials

PubMed Central

Gottlieb, Klaus; Dawson, Jill; Hussain, Fez; Murray, Joseph A.

2015-01-01

Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests. We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials, with a particular emphasis on current thinking in regulatory agencies. We conclude our paper with recommendations and a glossary of regulatory terms, to enable readers who are less familiar with regulatory language to take maximum advantage of this review. PMID:25725041

Leading trends in environmental regulation that affect energy development. Final report

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

Steele, R V; Attaway, L D; Christerson, J A

1980-01-01

Major environmental issues that are likely to affect the implementation of energy technologies between now and the year 2000 are identified and assessed. The energy technologies specifically addressed are: oil recovery and processing; gas recovery and processing; coal liquefaction; coal gasification (surface); in situ coal gasification; direct coal combustion; advanced power systems; magnetohydrodynamics; surface oil shale retorting; true and modified in situ oil shale retorting; geothermal energy; biomass energy conversion; and nuclear power (fission). Environmental analyses of these technologies included, in addition to the main processing steps, the complete fuel cycle from resource extraction to end use. A comprehensive surveymore » of the environmental community (including environmental groups, researchers, and regulatory agencies) was carried out in parallel with an analysis of the technologies to identify important future environmental issues. Each of the final 20 issues selected by the project staff has the following common attributes: consensus of the environmental community that the issue is important; it is a likely candidate for future regulatory action; it deals with a major environmental aspect of energy development. The analyses of the 20 major issues address their environmental problem areas, current regulatory status, and the impact of future regulations. These analyses are followed by a quantitative assessment of the impact on energy costs and nationwide pollutant emissions of possible future regulations. This is accomplished by employing the Strategic Environmental Assessment System (SEAS) for a subset of the 20 major issues. The report concludes with a more general discussion of the impact of environmental regulatory action on energy development.« less

Metabolomics in Toxicology and Preclinical Research

PubMed Central

Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

2013-01-01

Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

Analysis of environmental constraints on expanding reserves in current and future reservoirs in wetlands. Final report

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

Harder, B.J.

1995-03-01

Louisiana wetlands require careful management to allow exploitation of non-renewable resources without destroying renewable resources. Current regulatory requirements have been moderately successful in meeting this goal by restricting development in wetland habitats. Continuing public emphasis on reducing environmental impacts of resource development is causing regulators to reassess their regulations and operators to rethink their compliance strategies. We examined the regulatory system and found that reducing the number of applications required by going to a single application process and having a coherent map of the steps required for operations in wetland areas would reduce regulatory burdens. Incremental changes can be mademore » to regulations to allow one agency to be the lead for wetland permitting at minimal cost to operators. Operators need cost effective means of access that will reduce environmental impacts, decrease permitting time, and limit future liability. Regulators and industry must partner to develop incentive based regulations that can provide significant environmental impact reduction for minimal economic cost. In addition regulators need forecasts of future E&P trends to estimate the impact of future regulations. To determine future activity we attempted to survey potential operators when this approach was unsuccessful we created two econometric models of north and south Louisiana relating drilling activity, success ratio, and price to predict future wetland activity. Results of the econometric models indicate that environmental regulations have a small but statistically significant effect on drilling operations in wetland areas of Louisiana. We examined current wetland practices and evaluated those practices comparing environmental versus economic costs and created a method for ranking the practices.« less

Genetically Modified Food Labeling in China: In Pursuit of a Rational Path.

PubMed

Zhu, Xiao; Roberts, Michael T; Wu, Kaijie

2016-08-01

Facing a tension between the increasing use of genetically engineered or modified food and consumer concerns over the risks associated with GMOs, China has established a GM food labeling regime through regulations-known as Agro-GMO regulations-to protect consumers' right to know. However, the design and enforcement of this GM food labeling regime is problematic. As a result, the labeling regime is ineffective and inconsistent, leaving consumers' rights unprotected. As the recently amended Food Safety Law in China requires GM food labeling for the first time, this article argues that China should replace the current Agro-GMO food labeling scheme with a special regulatory scheme. A comparative analysis of the GM food labeling systems in the European Union and United States, coupled with a rigorous examination of the problems and barriers of GM food labeling in China, sets a solid foundation by which to propose changes to incorporate into a special regulatory scheme. To this end, this article engages in such an analysis and recommends practical steps to guide the enactment of a special regulatory scheme. The recommendations comport with China's unique legal and political culture, but also could be used by other national regulatory regimes who permit use of GM food while also being committed to improving consumers' right to know.

Meeting the challenges of medical countermeasure development.

PubMed

Maher, Carmen; Hu-Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-09-01

Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three-pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures - and the systems to deliver them - and the requisite support of all stakeholders, including national leadership. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Modeling stochasticity and robustness in gene regulatory networks.

PubMed

Garg, Abhishek; Mohanram, Kartik; Di Cara, Alessandro; De Micheli, Giovanni; Xenarios, Ioannis

2009-06-15

Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

PubMed Central

Koning, Anne; Kuhnle, Gunter G.C.; Nagy, Peter; Bianco, Christopher L.; Pasch, Andreas; Wink, David A.; Fukuto, Jon M.; Jackson, Alan A.; van Goor, Harry; Olson, Kenneth R.

2017-01-01

Abstract Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. Critical Issues: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Future Directions: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 27, 684–712. PMID:28398072

78 FR 79455 - Information Collection; System for Award Management Registration Requirements for Prime Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

...Under the provisions of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), the Regulatory Secretariat Division will be submitting to the Office of Management and Budget (OMB) a request to review and approve a renewal of the currently approved information collection requirement regarding the pre-award registration requirements for Prime Grant Recipients. The title of the approved information collection is Central Contractor Registration Requirements for Prime Grant Recipients (OMB Control Number 3090-0290). The updated information collection title, based on the migration of the Central Contractor Registration system to the System for Award Management in late July 2012, is System for Award Management Registration Requirements for Prime Grant Recipients.

EPA office of solid waste (OSW) report to Congress

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

Derkics, D.

1996-12-31

An EPA Office of Solid Waste Report to Congress is presented in outline form. The following topics are discussed: special waste chronology; statutory hazardous waste exemption; 1988 report to Congress findings; 1993 regulatory determination; current (1996), regulatory status of fossil fuel combustion wastes; co-management study; Electric Power Research Institute (EPRI) activities; EPRI coal ash field study sites; oil ash total combustion; fossil fuel combustion; current EPA activities; and Federal Register Notice.

40 CFR 142.304 - For which of the regulatory requirements is a small system variance available?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false For which of the regulatory requirements is a small system variance available? 142.304 Section 142.304 Protection of Environment... REGULATIONS IMPLEMENTATION Variances for Small System General Provisions § 142.304 For which of the regulatory...

Economic Implications of Potential Changes to Regulatory and Reimbursement Policies for Medical Devices

PubMed Central

Reed, Shelby D.; Shea, Alisa M.

2007-01-01

Objective To evaluate the impact of regulatory scenarios on the financial viability of medical device companies. Design We developed a model to calculate the expected net present value of a hypothetical product throughout preclinical development, clinical testing, regulatory approval, and postmarketing. We tested 3 scenarios: (1) the current regulatory environment; (2) a scenario in which medical devices are subject to the same evidence standards required for pharmaceuticals; and (3) a scenario consistent with the Coverage with Evidence Development: Coverage with Study Participation (CSP) policy proposed by the Centers for Medicare and Medicaid Services, whereby Medicare will pay for beneficiaries to receive new devices that are not currently determined to be “reasonable and necessary” if the patients participate in clinical studies or registries. Measurements and Main results When applying assumptions consistent with the implantable cardioverter-defibrillator market, the net present value at the start of development was an estimated $553 million in the current regulatory environment, $322 million in the pharmaceutical scenario, and $403 million in the CSP scenario. Sensitivity analyses showed that the device industry would likely be profitable in all 3 scenarios over a range of assumptions. Conclusions The environment in which the medical device industry operates is financially attractive. Furthermore, when compared with the alternative of applying the same evidence standards for pharmaceuticals to medical devices, the CSP policy offers improved financial incentives for medical device companies. PMID:18095045

Study of the regulatory issues affecting truck freight movement in the Midwest.

DOT National Transportation Integrated Search

2014-12-01

This project investigated regulatory issues that may affect or limit freight movement in Iowa and other Midwest states: Illinois, Kansas, : Minnesota, Missouri, Nebraska, South Dakota, and Wisconsin. Current state regulations for the following are re...

Photosensitivity: a current biological overview.

PubMed

Elkeeb, Dena; Elkeeb, Laila; Maibach, Howard

2012-12-01

The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects. To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U.S Food and Drug Administration and the European Union regulatory agencies). We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.

Genetic tools for the investigation of Roseobacter clade bacteria

PubMed Central

2009-01-01

Background The Roseobacter clade represents one of the most abundant, metabolically versatile and ecologically important bacterial groups found in marine habitats. A detailed molecular investigation of the regulatory and metabolic networks of these organisms is currently limited for many strains by missing suitable genetic tools. Results Conjugation and electroporation methods for the efficient and stable genetic transformation of selected Roseobacter clade bacteria including Dinoroseobacter shibae, Oceanibulbus indolifex, Phaeobacter gallaeciensis, Phaeobacter inhibens, Roseobacter denitrificans and Roseobacter litoralis were tested. For this purpose an antibiotic resistance screening was performed and suitable genetic markers were selected. Based on these transformation protocols stably maintained plasmids were identified. A plasmid encoded oxygen-independent fluorescent system was established using the flavin mononucleotide-based fluorescent protein FbFP. Finally, a chromosomal gene knockout strategy was successfully employed for the inactivation of the anaerobic metabolism regulatory gene dnr from D. shibae DFL12T. Conclusion A genetic toolbox for members of the Roseobacter clade was established. This provides a solid methodical basis for the detailed elucidation of gene regulatory and metabolic networks underlying the ecological success of this group of marine bacteria. PMID:20021642

Transcriptional and posttranscriptional regulation of cyanobacterial photosynthesis.

PubMed

Wilde, Annegret; Hihara, Yukako

2016-03-01

Cyanobacteria are well established model organisms for the study of oxygenic photosynthesis, nitrogen metabolism, toxin biosynthesis, and salt acclimation. However, in comparison to other model bacteria little is known about regulatory networks, which allow cyanobacteria to acclimate to changing environmental conditions. The current work has begun to illuminate how transcription factors modulate expression of different photosynthetic regulons. During the past few years, the research on other regulatory principles like RNA-based regulation showed the importance of non-protein regulators for bacterial lifestyle. Investigations on modulation of photosynthetic components should elucidate the contributions of all factors within the context of a larger regulatory network. Here, we focus on regulation of photosynthetic processes including transcriptional and posttranscriptional mechanisms, citing examples from a limited number of cyanobacterial species. Though, the general idea holds true for most species, important differences exist between various organisms, illustrating diversity of acclimation strategies in the very heterogeneous cyanobacterial clade. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof Conrad Mullineaux. Copyright © 2015 Elsevier B.V. All rights reserved.

Empirical Bayes method for reducing false discovery rates of correlation matrices with block diagonal structure.

PubMed

Pacini, Clare; Ajioka, James W; Micklem, Gos

2017-04-12

Correlation matrices are important in inferring relationships and networks between regulatory or signalling elements in biological systems. With currently available technology sample sizes for experiments are typically small, meaning that these correlations can be difficult to estimate. At a genome-wide scale estimation of correlation matrices can also be computationally demanding. We develop an empirical Bayes approach to improve covariance estimates for gene expression, where we assume the covariance matrix takes a block diagonal form. Our method shows lower false discovery rates than existing methods on simulated data. Applied to a real data set from Bacillus subtilis we demonstrate it's ability to detecting known regulatory units and interactions between them. We demonstrate that, compared to existing methods, our method is able to find significant covariances and also to control false discovery rates, even when the sample size is small (n=10). The method can be used to find potential regulatory networks, and it may also be used as a pre-processing step for methods that calculate, for example, partial correlations, so enabling the inference of the causal and hierarchical structure of the networks.

Regulatory Guidance for Lightning Protection in Nuclear Power Plants

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

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

2006-01-01

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

Regulatory guidance for lightning protection in nuclear power plants

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

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

2006-07-01

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

Bioattractors: dynamical systems theory and the evolution of regulatory processes.

PubMed

Jaeger, Johannes; Monk, Nick

2014-06-01

In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype-phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait--such as attractors with associated basins and their bifurcations--define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Regulatory networks between neurotrophins and miRNAs in brain diseases and cancers

PubMed Central

Shi, Jian

2015-01-01

Neurotrophins are involved in many physiological and pathological processes in the nervous system. They regulate and modify signal transduction, transcription and translation in neurons. It is recently demonstrated that the neurotrophin expression is regulated by microRNAs (miRNAs), changing our views on neurotrophins and miRNAs. Generally, miRNAs regulate neurotrophins and their receptors in at least two ways: (1) miRNAs bind directly to the 3′ untranslated region (UTR) of isoform-specific mRNAs and post-transcriptionally regulate their expression; (2) miRNAs bind to the 3′ UTR of the regulatory factors of neurotrophins and regulate their expression. On the other hand, neurotrophins can regulate miRNAs. The results of BNDF research show that neurotrophins regulate miRNAs in at least three ways: (1) ERK stimulation enhances the activation of TRBP (HIV-1 TAR RNA-binding protein) and Dicer, leading to the upregulation of miRNA biogenesis; (2) ERK-dependent upregulation of Lin28a (RNA-binding proteins) blocks select miRNA biogenesis; (3) transcriptional regulation of miRNA expression through activation of transcription factors, including CREB and NF-κB. These regulatory processes integrate positive and negative regulatory loops in neurotrophin and miRNA signaling pathways, and also expand the function of neurotrophins and miRNAs. In this review, we summarize the current knowledge of the regulatory networks between neurotrophins and miRNAs in brain diseases and cancers, for which novel cutting edge therapeutic, delivery and diagnostic approaches are emerging. PMID:25544363

Current Topics in Postnatal Behavioral Testing.

PubMed

Henck, Judith W; Elayan, Ikram; Vorhees, Charles; Fisher, J Edward; Morford, LaRonda L

2016-09-01

The study of developmental neurotoxicity (DNT) continues to be an important component of safety evaluation of candidate therapeutic agents and of industrial and environmental chemicals. Developmental neurotoxicity is considered to be an adverse change in the central and/or peripheral nervous system during development of an organism and has been primarily evaluated by studying functional outcomes, such as changes in behavior, neuropathology, neurochemistry, and/or neurophysiology. Neurobehavioral evaluations are a component of a wide range of toxicology studies in laboratory animal models, whereas neurochemistry and neurophysiology are less commonly employed. Although the primary focus of this article is on neurobehavioral evaluation in pre- and postnatal development and juvenile toxicology studies used in pharmaceutical development, concepts may also apply to adult nonclinical safety studies and Environmental Protection Agency/chemical assessments. This article summarizes the proceedings of a symposium held during the 2015 American College of Toxicology annual meeting and includes a discussion of the current status of DNT testing as well as potential issues and recommendations. Topics include the regulatory context for DNT testing; study design and interpretation; behavioral test selection, including a comparison of core learning and memory systems; age of testing; repeated testing of the same animals; use of alternative animal models; impact of findings; and extrapolation of animal results to humans. Integration of the regulatory experience and scientific concepts presented during this symposium, as well as from subsequent discussion and input, provides a synopsis of the current state of DNT testing in safety assessment, as well as a potential roadmap for future advancement. © The Author(s) 2016.

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

Regulatory sequence analysis tools.

PubMed

van Helden, Jacques

2003-07-01

The web resource Regulatory Sequence Analysis Tools (RSAT) (http://rsat.ulb.ac.be/rsat) offers a collection of software tools dedicated to the prediction of regulatory sites in non-coding DNA sequences. These tools include sequence retrieval, pattern discovery, pattern matching, genome-scale pattern matching, feature-map drawing, random sequence generation and other utilities. Alternative formats are supported for the representation of regulatory motifs (strings or position-specific scoring matrices) and several algorithms are proposed for pattern discovery. RSAT currently holds >100 fully sequenced genomes and these data are regularly updated from GenBank.

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia

PubMed Central

Gogarty, B

2003-01-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001. PMID:12672887

Strategies of bringing drug product marketing applications to meet current regulatory standards.

PubMed

Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

2015-08-01

In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

Current NRC Perspectives Concerning Primary Water Stress Corrosion Cracking

NASA Astrophysics Data System (ADS)

Alley, David; Dunn, Darrell

Materials currently used in nuclear power plants are reliable and are generally resistant to environmental degradation. However, occurrences of environmental degradation have been observed as the current fleet of reactors ages. Primary water stress corrosion cracking (PWSCC) is of particular interest to the US Nuclear Regulatory Commission (NRC). This paper provides a historical assessment of operating experience associated with PWSCC and welding issues associated with PWSCC resistant materials. The paper also considers the regulatory issues associated with PWSCC, especially those associated with gaps in the understanding of the behavior of PWSCC resistant material under actual reactor conditions.

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.

Protecting workers and the environment: An environmental NGO's perspective on nanotechnology

NASA Astrophysics Data System (ADS)

Balbus, John M.; Florini, Karen; Denison, Richard A.; Walsh, Scott A.

2007-01-01

Nanotechnology, the design and manipulation of materials at the atomic scale, may well revolutionize many of the ways our society manufactures products, produces energy, and treats diseases. New materials based on nanotechnology are already reaching the market in a wide variety of consumer products. Some of the observed properties of nanomaterials call into question the adequacy of current methods for determining hazard and exposure and for controlling resulting risks. Given the limitations of existing regulatory tools and policies, we believe two distinct kinds of initiatives are needed: first, a major increase in the federal investment in nanomaterial risk research; second, rapid development and implementation of voluntary standards of care pending development of adequate regulatory safeguards in the longer term. Several voluntary programs are currently at various stages of evolution, though the eventual outputs of each of these are still far from clear. Ultimately, effective regulatory safeguards are necessary to provide a level playing field for industry while adequately protecting human health and the environment. This paper reviews the existing toxicological literature on nanomaterials, outlines and analyzes the current regulatory framework, and provides our recommendations, as an environmental non-profit organization, for safe nanotechnology development.

RNAi technologies in agricultural biotechnology: The Toxicology Forum 40th Annual Summer Meeting.

PubMed

Sherman, James H; Munyikwa, Tichafa; Chan, Stephen Y; Petrick, Jay S; Witwer, Kenneth W; Choudhuri, Supratim

2015-11-01

During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The meeting session described herein focused on the technology of RNA interference (RNAi) in agriculture. The general process by which RNAi works, currently registered RNAi-based plant traits, example RNAi-based traits in development, potential use of double stranded RNA (dsRNA) as topically applied pesticide active ingredients, research related to the safety of RNAi, biological barriers to ingested dsRNA, recent regulatory RNAi science reviews, and regulatory considerations related to the use of RNAi in agriculture were discussed. Participants generally agreed that the current regulatory framework is robust and appropriate for evaluating the safety of RNAi employed in agricultural biotechnology and were also supportive of the use of RNAi to develop improved crop traits. However, as with any emerging technology, the potential range of future products, potential future regulatory frameworks, and public acceptance of the technology will continue to evolve. As such, continuing dialogue was encouraged to promote education of consumers and science-based regulations. Copyright © 2015 Elsevier Inc. All rights reserved.

ramR mutations affecting fluoroquinolone susceptibility in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198

PubMed Central

Baucheron, Sylvie; Le Hello, Simon; Doublet, Benoît; Giraud, Etienne; Weill, François-Xavier; Cloeckaert, Axel

2013-01-01

A screening for non-target mutations affecting fluoroquinolone susceptibility was conducted in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198. Among a panel of representative isolates (n = 27), covering the epidemic, only three showed distinct mutations in ramR resulting in enhanced expression of genes encoding the AcrAB-TolC efflux system and low increase in ciprofloxacin MIC. No mutations were detected in other regulatory regions of this efflux system. Ciprofloxacin resistance in serovar Kentucky ST198 is thus currently mainly due to multiple target gene mutations. PMID:23914184

A map of terminal regulators of neuronal identity in Caenorhabditis elegans

PubMed Central

2016-01-01

Our present day understanding of nervous system development is an amalgam of insights gained from studying different aspects and stages of nervous system development in a variety of invertebrate and vertebrate model systems, with each model system making its own distinctive set of contributions. One aspect of nervous system development that has been among the most extensively studied in the nematode Caenorhabditis elegans is the nature of the gene regulatory programs that specify hardwired, terminal cellular identities. I first summarize a number of maps (anatomical, functional, and molecular) that describe the terminal identity of individual neurons in the C. elegans nervous system. I then provide a comprehensive summary of regulatory factors that specify terminal identities in the nervous system, synthesizing these past studies into a regulatory map of cellular identities in the C. elegans nervous system. This map shows that for three quarters of all neurons in the C. elegans nervous system, regulatory factors that control terminal identity features are known. In‐depth studies of specific neuron types have revealed that regulatory factors rarely act alone, but rather act cooperatively in neuron‐type specific combinations. In most cases examined so far, distinct, biochemically unlinked terminal identity features are coregulated via cooperatively acting transcription factors, termed terminal selectors, but there are also cases in which distinct identity features are controlled in a piecemeal fashion by independent regulatory inputs. The regulatory map also illustrates that identity‐defining transcription factors are reemployed in distinct combinations in different neuron types. However, the same transcription factor can drive terminal differentiation in neurons that are unrelated by lineage, unrelated by function, connectivity and neurotransmitter deployment. Lastly, the regulatory map illustrates the preponderance of homeodomain transcription factors in the control of terminal identities, suggesting that these factors have ancient, phylogenetically conserved roles in controlling terminal neuronal differentiation in the nervous system. WIREs Dev Biol 2016, 5:474–498. doi: 10.1002/wdev.233 For further resources related to this article, please visit the WIREs website. PMID:27136279

Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states.

PubMed

Preston, Charles; Chahal, Harinder S; Porrás, Analia; Cargill, Lucette; Hinds, Maryam; Olowokure, Babatunde; Cummings, Rudolph; Hospedales, James

2016-05-01

Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. "Regionalization"-an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems-may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative's concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

Regulation of stem cell-based therapies in Canada: current issues and concerns.

PubMed

von Tigerstrom, Barbara; Nguyen, Thu Minh; Knoppers, Bartha Maria

2012-09-01

Stem cell therapies offer enormous potential for the treatment of a wide range of diseases and conditions. Despite the excitement over such advances, regulators are faced with the challenge of determining criteria to ensure stem cells and their products are safe and effective for human use. However, stem cell-based products and therapies present unique regulatory challenges because standard drug development models do not wholly apply given the complexity and diversity of these products and therapies. As a result, regulatory requirements are often unclear and ambiguous creating unnecessary barriers for research. In order to better understand the barriers that might affect Canadian stem cell researchers, we sought feedback from stakeholders regarding areas of uncertainty or concern about existing regulatory oversight of cell therapies. A selection of Canadian researchers and clinicians working in the area of stem cell research were interviewed to assess certain key questions: 1) whether current regulatory requirements are easily accessible and well understood; 2) whether regulatory requirements create important challenges or barriers; and 3) whether there is a need for further guidance on the issue. The results of this survey are summarized and compared to issues and concerns experienced in other countries, as reported in the literature, to identify challenges which may be on the horizon and to provide possible solutions for regulatory reform.

Mobile-bearing knee systems: ultra-high molecular weight polyethylene wear and design issues.

PubMed

Greenwald, A Seth; Heim, Christine S

2005-01-01

In June 2004, the U.S. Food and Drug Administration Orthopaedic Advisory Panel recommended the reclassification of mobile-bearing knee systems for general use. This reflects the increasing use of mobile-bearing knee systems internationally, which is currently limited in the United States by regulatory requirement. Mobile-bearing knee systems are distinguished from conventional, fixed-plateau systems in that they allow dual-surface articulation between an ultra-high molecular weight polyethylene insert and metallic femoral and tibial tray components. Their in vivo success is dependent on patient selection, design, and material choice, as well as surgical precision during implantation. Laboratory and clinical experience extending over 25 years with individual systems suggests that mobile-bearing knee systems represent a viable treatment option for patients with knee arthrosis.

Interplay of Dysphoria and Anxiety Sensitivity in Relation to Emotion Regulatory Cognitions of Smoking Among Treatment-seeking Smokers

PubMed Central

Garey, Lorra; Bakhshaie, Jafar; Brandt, Charles P.; Langdon, Kirsten J.; Kauffman, Brooke Y.; Schmidt, Norman B.; Leventhal, Adam M.; Zvolensky, Michael J.

2017-01-01

Background and Objectives There is evidence that anxiety sensitivity (AS) plays a role in the maintenance of smoking, yet there is little understanding of how AS interplays with other affective symptomatology variables that are also related to smoking, such as dysphoria. Therefore, the current cross-sectional study evaluated the interactive effects of AS and dysphoria on emotion regulatory cognitions, including smoking negative affect reduction expectancies, perceived barriers for cessation, and smoking-specific experiential avoidance. Method A total of 448 adult treatment-seeking daily smokers, who responded to study advertisements, were recruited to participate in a smoking cessation treatment trial (47.8% female; Mage = 37.2, SD =13.5). The current study utilized self-report baseline data from trial participants. Results After accounting for covariates, simple slope analyses revealed that AS was positively related to negative affect reduction expectancies (β = .03, p =.01), perceived barriers to cessation (β =.22, p = .002), and smoking avoidance and inflexibility (β =.07, p = .04), among smokers with lower (versus higher) levels of dysphoria. Conclusions The current findings suggest that higher levels of dysphoria may mitigate the relation between AS and emotion regulatory cognitions of smoking. Scientific Significance The current findings highlight the unique and additive clinical relevance of AS and dysphoria regarding emotion regulatory smoking cognitions that may impede quit success. PMID:27122303

The allowance exchange - ALEX

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

Mangis, J.K.; Miller, C.; Nicholas, J.

1997-12-31

The success of market approaches to pollution control in reducing the cost of compliance with environmental regulation, has insured the inclusion of emissions trading programs in current and future regulatory programs. As these environmental trading programs multiply, (SO{sub 2}, NO{sub x}, Ozone Precursors, Wetlands, CO{sub 2} and others), utility companies will need a central location to buy, sell, and trade these allowances to meet regulatory needs. In response, SAIC has designed and prototyped an electronic trading system that can provide a common forum for the location and exchange of environmental allowances, marketable permits, and other market based instruments for environmentalmore » management. SAIC intends to open and operate the Allowance Exchange (ALEX) for the trading of all environmental allowances, associated with the operation of electric utilities, as a service to the nation, the industry, and the environmental community.« less

Nuclear Forensic Science: Analysis of Nuclear Material Out of Regulatory Control

NASA Astrophysics Data System (ADS)

Kristo, Michael J.; Gaffney, Amy M.; Marks, Naomi; Knight, Kim; Cassata, William S.; Hutcheon, Ian D.

2016-06-01

Nuclear forensic science seeks to identify the origin of nuclear materials found outside regulatory control. It is increasingly recognized as an integral part of a robust nuclear security program. This review highlights areas of active, evolving research in nuclear forensics, with a focus on analytical techniques commonly employed in Earth and planetary sciences. Applications of nuclear forensics to uranium ore concentrates (UOCs) are discussed first. UOCs have become an attractive target for nuclear forensic researchers because of the richness in impurities compared to materials produced later in the fuel cycle. The development of chronometric methods for age dating nuclear materials is then discussed, with an emphasis on improvements in accuracy that have been gained from measurements of multiple radioisotopic systems. Finally, papers that report on casework are reviewed, to provide a window into current scientific practice.

Inferring Time-Varying Network Topologies from Gene Expression Data

PubMed Central

2007-01-01

Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster—to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence. PMID:18309363

Inferring time-varying network topologies from gene expression data.

PubMed

Rao, Arvind; Hero, Alfred O; States, David J; Engel, James Douglas

2007-01-01

Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster--to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence.

Chinese vaccine products go global: vaccine development and quality control.

PubMed

Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

2015-05-01

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

Work Smarter Not Harder: Utilizing an Environmental Management Information System to Meet Regulatory Compliance and Reporting Requirements for a Major Source Title V Facility

DTIC Science & Technology

2011-05-10

Environmental Management Information System to Meet Regulatory Compliance and Reporting Requirements for a Major Source Title V Facility. Tannis Danley...AND SUBTITLE Work Smarter Not Harder: Utilizing an Environmental Management Information System to Meet Regulatory Compliance and Reporting...Carson) – EMS (Hawaii Garrison, West Virginia National Guard) Environmental Management Information System (EMIS) National Defense Center for Energy and

A structured policy review of the principles of professional self-regulation.

PubMed

Benton, D C; González-Jurado, M A; Beneit-Montesinos, J V

2013-03-01

The International Council of Nurses (ICN) has, for many years, based its work on professional self-regulation on a set of 12 principles. These principles are research based and were identified nearly three decades ago. ICN has conducted a number of reviews of the principles; however, changes have been minimal. In the past 5-10 years, a number of authors and governments, often as part of the review of regulatory systems, have started to propose principles to guide the way regulatory frameworks are designed and implemented. These principles vary in number and content. This study examines the current policy literature on principle-based regulation and compares this with the set of principles advocated by the ICN. A systematic search of the literature on principle-based regulation is used as the basis for a qualitative thematic analysis to compare and contrast the 12 principles of self-regulation with more recently published work. A mapping of terms based on a detailed description of the principles used in the various research and policy documents was generated. This mapping forms the basis of a critique of the current ICN principles. A professional self-regulation advocated by the ICN were identified. A revised and extended set of 13 principles is needed if contemporary developments in the field of regulatory frameworks are to be accommodated. These revised principles should be considered for adoption by the ICN to underpin their advocacy work on professional self-regulation. © 2013 The Authors. International Nursing Review © 2013 International Council of Nurses.

Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations

PubMed Central

Lai, Huafang; Chen, Qiang

2012-01-01

Despite the success in expressing a variety of subunit vaccine proteins in plants and the recent stride in improving vaccine accumulation levels by transient expression systems, there is still no plant-derived vaccine that has been licensed for human use. The lack of commercial success of plant-made vaccines lies in several technical and regulatory barriers that remain to be overcome. These challenges include the lack of scalable downstream processing procedures, the uncertainty of regulatory compliance of production processes, and the lack of demonstration of plant-derived products that meet the required standards of regulatory agencies in identity, purity, potency and safety. In this study, we addressed these remaining challenges and successfully demonstrate the ability of using plants to produce a pharmaceutical grade Norwalk virus (NV) vaccine under current Good Manufacture Practice (cGMP) guidelines at multiple gram scales. Our results demonstrate that an efficient and scalable extraction and purification scheme can established for processing virus-like particles (VLP) of NV capsid protein (NVCP). We successfully operated the upstream and downstream NVCP production processes under cGMP regulations. Furthermore, plant-derived NVCP VLP demonstrates the identity, purity, potency and safety that meet the preset release specifications. This material is being tested in a Phase I human clinical trial. This research provides the first report of producing a plant-derived vaccine at scale under cGMP regulations in an academic setting and an important step for plant-produced vaccines to become a commercial reality. PMID:22134876

Use of physiologically relevant biopharmaceutics tools within the pharmaceutical industry and in regulatory sciences: Where are we now and what are the gaps?

PubMed

Flanagan, Talia; Van Peer, Achiel; Lindahl, Anders

2016-08-25

Regulatory interactions are an important part of the drug development and licensing process. A survey on the use of biopharmaceutical tools for regulatory purposes has been carried out within the industry community of the EU project OrBiTo within Innovative Medicines Initiative (IMI). The aim was to capture current practice and experience in using in vitro and in silico biopharmaceutics tools at various stages of development, what barriers exist or are perceived, and to understand the current gaps in regulatory biopharmaceutics. The survey indicated that biorelevant dissolution testing and physiologically based modelling and simulation are widely applied throughout development to address a number of biopharmaceutics issues. However, data from these in vitro and in silico predictive biopharmaceutics tools are submitted to regulatory authorities far less often than they are used for internal risk assessment and decision making. This may prevent regulators from becoming familiar with these tools and how they are applied in industry, and limits the opportunities for biopharmaceutics scientists working in industry to understand the acceptability of these tools in the regulatory environment. It is anticipated that the advanced biopharmaceutics tools and understanding delivered in the next years by OrBiTo and other initiatives in the area of predictive tools will also be of value in the regulatory setting, and provide a basis for more informed and confident biopharmaceutics risk assessment and regulatory decision making. To enable the regulatory potential of predictive biopharmaceutics tools to be realized, further scientific dialogue is needed between industry, regulators and scientists in academia, and more examples need to be published to demonstrate the applicability of these tools. Copyright © 2016 Elsevier B.V. All rights reserved.

The National Shipbuilding Research Program. Analysis of Wash Water Treatment Efficiency for Copper and Zinc

DTIC Science & Technology

2000-12-15

per trillion for tributyltin (“ TBT ”). This regulatory action lead to an intensive research effort to develop a treatment method for ship’s wash water...antifoulant coating systems, including tributyltin , copper and zinc. In 1997 The Commonwealth of Virginia established an effluent discharge limit of 50 parts...waste stream that could consistently remove TBT to levels below this discharge standard. This work is currently being performed by the Center for

Post market surveillance in the german medical device sector - current state and future perspectives.

PubMed

Zippel, Claus; Bohnet-Joschko, Sabine

2017-08-01

Medical devices play a central role in the diagnosis and treatment of diseases but also bring the potential for adverse events, hazards or malfunction with serious consequences for patients and users. Medical device manufacturers are therefore required by law to monitor the performance of medical devices that have been approved by the competent authorities (post market surveillance). Conducting a nationwide online-survey in the German medical device sector in Q2/2014 in order to explore the current status of the use of post market instruments we obtained a total of 118 complete data sets, for a return rate of 36%. The survey included manufacturers of different sizes, producing medical devices of all risk classes. The post market instruments most frequently reported covered the fields of production monitoring and quality management as well as literature observation, regulatory vigilance systems, customer knowledge management and market observation while Post Market Clinical Follow-up and health services research were being used less for product monitoring. We found significant differences between the different risk classes of medical devices produced and the intensity of use of post market instruments. Differences between company size and the intensity of instruments used were hardly detected. Results may well contribute to the development of device monitoring which is a crucial element of the policy and regulatory system to identify device-related safety issues. Copyright © 2017 Elsevier B.V. All rights reserved.

12 CFR 233.7 - Regulatory enforcement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory...

12 CFR 233.7 - Regulatory enforcement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory...

12 CFR 233.7 - Regulatory enforcement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory...

12 CFR 233.7 - Regulatory enforcement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory enforcement. The...

12 CFR 233.7 - Regulatory enforcement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory enforcement. The...

The Dessau workshop on bioaccumulation: state of the art, challenges and regulatory implications.

PubMed

Treu, Gabriele; Drost, Wiebke; Jöhncke, Ulrich; Rauert, Caren; Schlechtriem, Christian

2015-01-01

Bioaccumulation plays a vital role in understanding the fate of a substance in the environment and is key to the regulation of chemicals in several jurisdictions. The current assessment approaches commonly use the octanol-water partition coefficient (log K OW ) as an indicator for bioaccumulation and the bioconcentration factor (BCF) as a standard criterion to identify bioaccumulative substances show limitations. The log K OW does not take into account active transport phenomena or special structural properties (e.g., amphiphilic substances or dissociating substances) and therefore additional screening criteria are required. Regulatory BCF studies are so far restricted to fish and uptake through the gills. Studies on (terrestrial) air-breathing organisms are missing. Though there are alternative tests such as the dietary exposure bioaccumulation fish test described in the recently revised OECD test guideline 305, it still remains unclear how to deal with results of alternative tests in regulatory decision-making processes. A substantial number of bioaccumulation fish tests are required in regulation. The development of improved test systems following the 3R principles, namely to replace, reduce and refine animal testing, is thus required. All these aspects stress the importance to further develop the assessment of bioaccumulation. The Dessau Workshop on Bioaccumulation which was held from June 26th to 27th 2014, in Dessau, Germany, provided a comprehensive overview of the state of the art of bioaccumulation assessment, provided insights into the problems and challenges addressed by the regulatory authorities and described new research concepts and their regulatory implications. The event was organised by UBA (Dessau, Germany) and Fraunhofer IME (Schmallenberg, Germany). About 50 participants from industry, regulatory bodies and academia listened to 14 lectures on selected topics and joined the plenary discussions.

Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

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

MULKEY, C.H.

1999-07-06

This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through themore » DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants.« less

Recommendations for the treatment of aging in standard technical specifications

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

Orton, R.D.; Allen, R.P.

1995-09-01

As part of the US Nuclear Regulatory Commission`s Nuclear Plant Aging Research Program, Pacific Northwest Laboratory (PNL) evaluated the standard technical specifications for nuclear power plants to determine whether the current surveillance requirements (SRs) were effective in detecting age-related degradation. Nuclear Plant Aging Research findings for selected systems and components were reviewed to identify the stressors and operative aging mechanisms and to evaluate the methods available to detect, differentiate, and trend the resulting aging degradation. Current surveillance and testing requirements for these systems and components were reviewed for their effectiveness in detecting degraded conditions and for potential contributions to prematuremore » degradation. When the current surveillance and testing requirements appeared ineffective in detecting aging degradation or potentially could contribute to premature degradation, a possible deficiency in the SRs was identified that could result in undetected degradation. Based on this evaluation, PNL developed recommendations for inspection, surveillance, trending, and condition monitoring methods to be incorporated in the SRs to better detect age- related degradation of these selected systems and components.« less

Resolving the problem of compliance with the ever increasing and changing regulations

NASA Astrophysics Data System (ADS)

Leigh, Harley

1992-01-01

The most common problem identified at several U.S. Department of Energy (DOE) sites is regulatory compliance. Simply, the project viability depends on identifying regulatory requirements at the beginning of a specific project to avoid possible delays and cost overruns. The Radioisotope Power Systems Facility (RPSF) is using the Regulatory Compliance System (RCS) to deal with the problem that well over 1000 regulatory documents had to be reviewed for possible compliance requirements applicable to the facility. This overwhelming number of possible documents is not atypical of all DOE facilities thus far reviewed using the RCS system. The RCS was developed to provide control and tracking of all the regulatory and institutional requirements on a given project. WASTREN, Inc., developed the RCS through various DOE contracts and continues to enhance and update the system for existing and new contracts. The RCS provides the information to allow the technical expert to assimilate and manage accurate resource information, compile the necessary checklists, and document that the project or facility fulfills all of the appropriate regulatory requirements. The RCS provides on-line information, including status throughout the project life, thereby allowing more intelligent and proactive decision making. Also, consistency and traceability are provided for regulatory compliance documentation.

National ethics guidance in Sub-Saharan Africa on the collection and use of human biological specimens: a systematic review.

PubMed

Barchi, Francis; Little, Madison T

2016-10-22

Ethical and regulatory guidance on the collection and use of human biospecimens (HBS) for research forms an essential component of national health systems in Sub-Saharan Africa (SSA), where rapid advances in genetic- and genomic-based technologies are fueling clinical trials involving HBS and the establishment of large-scale biobanks. An extensive multi-level search for publicly available ethics regulatory guidance was conducted for each SSA country. A second review documented active trials listed in the WHO International Clinical Trials Registry Platform as of January 2015 in which HBS collection was specified in the protocol. Findings were combined to determine the extent to which countries that are study sites for HBS-related research are supported by regulatory guidance language on the collection, use, ownership and storage of biospecimens. Of the 49 SSA countries, 29 had some form of national ethics guidance, yet only 17 provided language relating to HBS-related research, with specific guidance on consent (14), ownership (6), reuse (10), storage (9), and export/import/transfer (13). Ten countries accounted for 84 % of the active clinical trials involving the collection of HBS in SSA. All except one of these countries were found to have some national guidance in the form of regulations, codes of ethics, and/or standard operating procedures; however, only seven of the ten offered any language specific to HBS. Despite the fact that the bulk of registered clinical trials in SSA involving HBS, as well as existing and proposed sites for biorepositories under the H3Africa Initiative, are currently situated in countries with the most complete ethics and regulatory guidance, variability in the regulations themselves may create challenges for planned and future pan-African collaborations and may require legislative action at the national level to revise. Countries in SSA that still lack regulatory guidance on HBS will require extensive health system strengthening in ethics governance before they can be full participants in the modern research enterprise.

Gene network analysis: from heart development to cardiac therapy.

PubMed

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

2015-03-01

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

Biological Signal Processing with a Genetic Toggle Switch

PubMed Central

Hillenbrand, Patrick; Fritz, Georg; Gerland, Ulrich

2013-01-01

Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, which processes the input signals and the memory content, is often not well understood. Here, we explore design constraints for such regulatory interfaces using coarse-grained nonlinear models and stochastic simulations of detailed biochemical reaction networks. We test different designs for biological analogs of the most versatile memory element in digital electronics, the JK-latch. Our analysis shows that simple protein-protein interactions and protein-DNA binding are sufficient, in principle, to implement genetic circuits with the capabilities of a JK-latch. However, it also exposes fundamental limitations to its reliability, due to the fact that biological signal processing is asynchronous, in contrast to most digital electronics systems that feature a central clock to orchestrate the timing of all operations. We describe a seemingly natural way to improve the reliability by invoking the master-slave concept from digital electronics design. This concept could be useful to interpret the design of natural regulatory circuits, and for the design of synthetic biological systems. PMID:23874595

Regulatory Impact Analysis (RIA) for the Proposed Revisions to the Sulfur Dioxide National Ambient Air Quality Standards (NAAQS)

EPA Pesticide Factsheets

This Regulatory Impact Analysis (RIA) provides estimates of the incremental costs and monetized human health benefits of attaining a revised short‐term Sulfur Dioxide (SO2) NAAQS within the current monitoring network.

Best Practices for Use of Historical Control Data of Proliferative Rodent Lesions.

EPA Science Inventory

The Historical Control Data Working Group under the direction of the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) was tasked with reviewing the current scientific practices, regulatory guidance and relevant literature pertaining ...

Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor

PubMed Central

Hovingh, Elise S.; de Maat, Steven; Cloherty, Alexandra P. M.; Johnson, Steven; Pinelli, Elena; Maas, Coen; Jongerius, Ilse

2018-01-01

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence. PMID:29915576

Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.

PubMed

Hovingh, Elise S; de Maat, Steven; Cloherty, Alexandra P M; Johnson, Steven; Pinelli, Elena; Maas, Coen; Jongerius, Ilse

2018-01-01

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis . Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence.

Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options

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

Carter, Sarah R.; Rodemeyer, Michael; Garfinkel, Michele S.

Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options Sarah R. Carter, Ph.D., J. Craig Venter Institute; Michael Rodemeyer, J.D., University of Virginia; Michele S. Garfinkel, Ph.D., EMBO; Robert M. Friedman, Ph.D., J. Craig Venter Institute In recent years, a range of genetic engineering techniques referred to as “synthetic biology” has significantly expanded the tool kit available to scientists and engineers, providing them with far greater capabilities to engineer organisms than previous techniques allowed. The field of synthetic biology includes the relatively new ability to synthesize long pieces of DNA from chemicals, as well as improved methods formore » genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic engineering techniques will leave many engineered plants without any pre-market regulatory review. Second, the number and diversity of engineered microbes for commercial use will increase in the near future, challenging EPA’s resources, expertise, and perhaps authority to regulate them. For each of these challenges, the report sets out a series of options, including an analysis of the advantages and disadvantages of each option from a variety of perspectives, for policy makers to consider. Policy responses will depend on the trade-offs chosen among competing considerations. This report, funded by the Department of Energy with additional funds from the Alfred P. Sloan Foundation, is the result of a two-year process that included interviews, commissioned background papers, discussions, and two workshops that sought input from a wide range of experts, including U.S. federal agency regulators, legal and science policy experts, representatives from the biotechnology indus¬try, and non-governmental organiza¬tions. This cross-section of views informed this report, but the conclusions are solely those of the authors. An Executive Summary, full Report, and background papers are available at: http://www.jcvi.org/cms/research/projects/synthetic-biology-and-the-us-biotechnology-regulatory-system/overview/« less

Transcriptional regulatory proteins as biosensing tools.

PubMed

Turner, Kendrick; Joel, Smita; Feliciano, Jessika; Feltus, Agatha; Pasini, Patrizia; Wynn, Daniel; Dau, Peter; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

2017-06-22

We have developed sensing systems employing different classes of transcriptional regulatory proteins genetically and chemically modified to incorporate a fluorescent reporter molecule for detection of arsenic, hydroxylated polychlorinated biphenyls (OH-PCBs), and cyclic AMP (cAMP). These are the first examples of optical sensing systems based on transcriptional regulatory proteins.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

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

Preventing type 2 diabetes: Changing the food industry.

PubMed

Popkin, Barry M; Kenan, W R

2016-06-01

Improving our global diet by working with the food industry is a fairly complex task. Previously the global food manufacturing companies and governments were the major players. However, matters have shifted rapidly so that food retailers, food manufacturers, the restaurant-food service sector, and agribusinesses are now the major players. The current modern system of packaged processed food has now penetrated the globe-rich and poor, rural and urban are all in reach of this food system. Consequently, working with this complex sector when possible and an array of governmental regulatory large-scale options to improve our diet have increased in importance. Taxation of unhealthy foods and beverages, marketing controls, and front of the package labeling are the primary current options. Evaluations of the impacts of both public and industry initiatives are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Challenges and regulatory considerations in the acoustic measurement of high-frequency (>20 MHz) ultrasound.

PubMed

Nagle, Samuel M; Sundar, Guru; Schafer, Mark E; Harris, Gerald R; Vaezy, Shahram; Gessert, James M; Howard, Samuel M; Moore, Mary K; Eaton, Richard M

2013-11-01

This article examines the challenges associated with making acoustic output measurements at high ultrasound frequencies (>20 MHz) in the context of regulatory considerations contained in the US Food and Drug Administration industry guidance document for diagnostic ultrasound devices. Error sources in the acoustic measurement, including hydrophone calibration and spatial averaging, nonlinear distortion, and mechanical alignment, are evaluated, and the limitations of currently available acoustic measurement instruments are discussed. An uncertainty analysis of acoustic intensity and power measurements is presented, and an example uncertainty calculation is done on a hypothetical 30-MHz high-frequency ultrasound system. This analysis concludes that the estimated measurement uncertainty of the acoustic intensity is +73%/-86%, and the uncertainty in the mechanical index is +37%/-43%. These values exceed the respective levels in the Food and Drug Administration guidance document of 30% and 15%, respectively, which are more representative of the measurement uncertainty associated with characterizing lower-frequency ultrasound systems. Recommendations made for minimizing the measurement uncertainty include implementing a mechanical positioning system that has sufficient repeatability and precision, reconstructing the time-pressure waveform via deconvolution using the hydrophone frequency response, and correcting for hydrophone spatial averaging.

Resilience of Cyber Systems with Over- and Underregulation.

PubMed

Gisladottir, Viktoria; Ganin, Alexander A; Keisler, Jeffrey M; Kepner, Jeremy; Linkov, Igor

2017-09-01

Recent cyber attacks provide evidence of increased threats to our critical systems and infrastructure. A common reaction to a new threat is to harden the system by adding new rules and regulations. As federal and state governments request new procedures to follow, each of their organizations implements their own cyber defense strategies. This unintentionally increases time and effort that employees spend on training and policy implementation and decreases the time and latitude to perform critical job functions, thus raising overall levels of stress. People's performance under stress, coupled with an overabundance of information, results in even more vulnerabilities for adversaries to exploit. In this article, we embed a simple regulatory model that accounts for cybersecurity human factors and an organization's regulatory environment in a model of a corporate cyber network under attack. The resulting model demonstrates the effect of under- and overregulation on an organization's resilience with respect to insider threats. Currently, there is a tendency to use ad-hoc approaches to account for human factors rather than to incorporate them into cyber resilience modeling. It is clear that using a systematic approach utilizing behavioral science, which already exists in cyber resilience assessment, would provide a more holistic view for decisionmakers. © 2016 Society for Risk Analysis.

The forecast for RAC extrapolation: mostly cloudy.

PubMed

Goldman, Elizabeth; Jacobs, Robert; Scott, Ellen; Scott, Bonnie

2011-09-01

The current statutory and regulatory guidance for recovery audit contractor (RAC) extrapolation leaves providers with minimal protection against the process and a limited ability to challenge overpayment demands. Providers not only should understand the statutory and regulatory basis for extrapolation forecast, but also should be able to assess their extrapolation risk and their recourse through regulatory safeguards against contractor error. Providers also should aggressively appeal all incorrect RAC denials to minimize the potential impact of extrapolation.

Classification and Analysis of Regulatory Pathways Using Graph Property, Biochemical and Physicochemical Property, and Functional Property

PubMed Central

Cai, Yu-Dong; Chou, Kuo-Chen

2011-01-01

Given a regulatory pathway system consisting of a set of proteins, can we predict which pathway class it belongs to? Such a problem is closely related to the biological function of the pathway in cells and hence is quite fundamental and essential in systems biology and proteomics. This is also an extremely difficult and challenging problem due to its complexity. To address this problem, a novel approach was developed that can be used to predict query pathways among the following six functional categories: (i) “Metabolism”, (ii) “Genetic Information Processing”, (iii) “Environmental Information Processing”, (iv) “Cellular Processes”, (v) “Organismal Systems”, and (vi) “Human Diseases”. The prediction method was established trough the following procedures: (i) according to the general form of pseudo amino acid composition (PseAAC), each of the pathways concerned is formulated as a 5570-D (dimensional) vector; (ii) each of components in the 5570-D vector was derived by a series of feature extractions from the pathway system according to its graphic property, biochemical and physicochemical property, as well as functional property; (iii) the minimum redundancy maximum relevance (mRMR) method was adopted to operate the prediction. A cross-validation by the jackknife test on a benchmark dataset consisting of 146 regulatory pathways indicated that an overall success rate of 78.8% was achieved by our method in identifying query pathways among the above six classes, indicating the outcome is quite promising and encouraging. To the best of our knowledge, the current study represents the first effort in attempting to identity the type of a pathway system or its biological function. It is anticipated that our report may stimulate a series of follow-up investigations in this new and challenging area. PMID:21980418

Laser Communication Demonstration System (LCDS) and future mobile satellite services

NASA Technical Reports Server (NTRS)

Chen, Chien-Chung; Wilhelm, Michael D.; Lesh, James R.

1995-01-01

The Laser Communications Demonstration System (LCDS) is a proposed in-orbit demonstration of high data rate laser communications technology conceived jointly by NASA and U.S. industry. The program objectives are to stimulate industry development and to demonstrate the readiness of high data rate optical communications in Earth orbit. For future global satellite communication systems using intersatellite links, laser communications technology can offer reduced mass and power requirements and higher channel bandwidths without regulatory constraints. As currently envisioned, LCDS will consist of one or two orbiting laser communications terminals capable of demonstrating high data rate (greater than 750Mbps) transmission in a dynamic space environment. Two study teams led by Motorola and Ball Aerospace are currently in the process of conducting a Phase A/B mission definition study of LCDS under contracts with JPL/NASA. The studies consist of future application survey, concept and requirements definition, and a point design of the laser communications flight demonstration. It is planned that a single demonstration system will be developed based on the study results. The Phase A/B study is expected to be completed by the coming June, and the current results of the study are presented in this paper.

Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

PubMed

Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

2017-10-01

The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

76 FR 32878 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-07

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

Bottom-up GGM algorithm for constructing multiple layered hierarchical gene regulatory networks

USDA-ARS?s Scientific Manuscript database

Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. A bottom-up graphic Gaus...

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...

21 CFR 26.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... regulatory systems means that the systems are sufficiently comparable to assure that the process of... require that the respective regulatory systems have identical procedures. (c) Good Manufacturing Practices...

Rationale for Selection of Pesticides, Herbicides, and Related Compounds from the Hanford SST/DST Waste Considered for Analysis in Support of the Regulatory DQO (Privatization)

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

Wiemers, K.D.; Daling, P.; Meier, K.

1999-01-04

Regulated pesticides, herbicides, miticides, and fungicides were evaluated for their potential past and current use at the Hanford Site. The starting list of these compounds is based on regulatory analyte input lists discussed in the Regulatory DQO. Twelve pesticide, herbicide, miticide, and fungicide compounds are identified for analysis in the Hanford SST and DST waste in support of the Regulatory DQO. The compounds considered for additional analyses are non-detected, considered stable in the tank waste matrix, and of higher toxicity/carcinogenicity.

RCRA, superfund and EPCRA hotline training module. Introduction to: RCRA corrective action updated July 1996

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

NONE

1996-07-01

The module discusses the regulatory and statutory requirements and authorities governing the Resource Conservation and Recovery Act (RCRA) corrective action process. There are minimal regulatory requirements at present, but the Agency has issued a proposed rule (55 FR 30798; July 27, 1990) that would establish a comprehensive regulatory framework for implementing the corrective action program. This proposed rule and other guidance developed pursuant to statutory authorities are used to structure corrective action requirements in facility permits and orders. This module describes the current statutory and regulatory structure and discusses the future of the proposed rule.

Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

PubMed

Zetterqvist, Anna V; Mulinari, Shai

2013-01-01

The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self-regulatory settings, and if appropriate measures are not taken to amend shortcomings, many countries may want to reconsider the current balance between self-regulation, and legislative control with government oversight.

Fifty years of the European medicines regulatory network: reflections for strengthening intra-regional cooperation in the Region of the Americas.

PubMed

Allchurch, Martin Harvey; Barbano, Dirceu Brás Aparecido; Pinheiro, Marie-Hélène; Lazdin-Helds, Janis

2016-05-01

This report considers how the experience of the European regulatory system might be applied to help strengthen the regulatory systems for medicines in the Region of the Americas. The work of the European Medicines Agencies (EMA) is carried out through its scientific committees, composed of members from European Economic Area countries. A robust legal framework allows EMA to coordinate resources from Member States' competent authorities, including, for example, assisting candidate countries as they prepare to join the European Union (EU). Capacity-building programs help countries adjust their regulatory systems ahead of full participation in the European medicines regulatory network. These programs facilitate adoption of common technical requirements, identify areas where action might be needed to ensure the smooth transposition of EU pharmaceutical law into national legislation, and prepare candidate countries for participation in EMA committees and the European regulatory network. The methodology of these programs could be of potential interest to the Pan American Health Organization (PAHO), the Regional Office of the World Health Organization for the Americas. Given resolutions adopted by the World Health Assembly and the PAHO Directing Council, there is a strong indication that the countries of the Region of the Americas wish to assemble a system that uses the existing regulatory capacity of some countries to strengthen local regulatory capacities in others.

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks

PubMed Central

Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P.; Gerstein, Mark

2010-01-01

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers’ continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems. PMID:20439753

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

PubMed

Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P; Gerstein, Mark

2010-05-18

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

Thermal pollution impacts on rivers and power supply in the Mississippi River watershed

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

Miara, Ariel; Vorosmarty, Charles J.; Macknick, Jordan E.

Thermal pollution from power plants degrades riverine ecosystems with ramifications beyond the natural environment as it affects power supply. The transport of thermal effluents along river reaches may lead to plant-to-plant interferences by elevating condenser inlet temperatures at downstream locations, which lower thermal efficiencies and trigger regulatory-forced power curtailments. We evaluate thermal pollution impacts on rivers and power supply across 128 plants with once-through cooling technologies in the Mississippi River watershed. By leveraging river network topologies with higher resolutions (0.05 degrees) than previous studies, we reveal the need to address the issue in a more spatially resolved manner, capable ofmore » uncovering diverse impacts across individual plants, river reaches and sub-basins. Results show that the use of coarse river network resolutions may lead to substantial overestimations in magnitude and length of impaired river reaches. Overall, there is a modest limitation on power production due to thermal pollution, given existing infrastructure, regulatory and climate conditions. However, tradeoffs between thermal pollution and electricity generation show important implications for the role of alternative cooling technologies and environmental regulation under current and future climates. Recirculating cooling technologies may nearly eliminate thermal pollution and improve power system reliability under stressed climate-water conditions. Regulatory limits also reduce thermal pollution, but at the expense of significant reductions in electricity generation capacity. However, results show several instances when power production capacity rises at individual plants when regulatory limits reduce upstream thermal pollution. Furthermore, these dynamics across energy-water systems highlight the need for high-resolution simulations and the value of coherent planning and optimization across infrastructure with mutual dependencies on natural resources to overcome climate-water constraints on productivity and bring to fruition energy and environmental win-win opportunities.« less

Thermal pollution impacts on rivers and power supply in the Mississippi River watershed

DOE PAGES

Miara, Ariel; Vorosmarty, Charles J.; Macknick, Jordan E.; ...

2018-03-08

Thermal pollution from power plants degrades riverine ecosystems with ramifications beyond the natural environment as it affects power supply. The transport of thermal effluents along river reaches may lead to plant-to-plant interferences by elevating condenser inlet temperatures at downstream locations, which lower thermal efficiencies and trigger regulatory-forced power curtailments. We evaluate thermal pollution impacts on rivers and power supply across 128 plants with once-through cooling technologies in the Mississippi River watershed. By leveraging river network topologies with higher resolutions (0.05 degrees) than previous studies, we reveal the need to address the issue in a more spatially resolved manner, capable ofmore » uncovering diverse impacts across individual plants, river reaches and sub-basins. Results show that the use of coarse river network resolutions may lead to substantial overestimations in magnitude and length of impaired river reaches. Overall, there is a modest limitation on power production due to thermal pollution, given existing infrastructure, regulatory and climate conditions. However, tradeoffs between thermal pollution and electricity generation show important implications for the role of alternative cooling technologies and environmental regulation under current and future climates. Recirculating cooling technologies may nearly eliminate thermal pollution and improve power system reliability under stressed climate-water conditions. Regulatory limits also reduce thermal pollution, but at the expense of significant reductions in electricity generation capacity. However, results show several instances when power production capacity rises at individual plants when regulatory limits reduce upstream thermal pollution. Furthermore, these dynamics across energy-water systems highlight the need for high-resolution simulations and the value of coherent planning and optimization across infrastructure with mutual dependencies on natural resources to overcome climate-water constraints on productivity and bring to fruition energy and environmental win-win opportunities.« less

Thermal pollution impacts on rivers and power supply in the Mississippi River watershed

NASA Astrophysics Data System (ADS)

Miara, Ariel; Vörösmarty, Charles J.; Macknick, Jordan E.; Tidwell, Vincent C.; Fekete, Balazs; Corsi, Fabio; Newmark, Robin

2018-03-01

Thermal pollution from power plants degrades riverine ecosystems with ramifications beyond the natural environment as it affects power supply. The transport of thermal effluents along river reaches may lead to plant-to-plant interferences by elevating condenser inlet temperatures at downstream locations, which lower thermal efficiencies and trigger regulatory-forced power curtailments. We evaluate thermal pollution impacts on rivers and power supply across 128 plants with once-through cooling technologies in the Mississippi River watershed. By leveraging river network topologies with higher resolutions (0.05°) than previous studies, we reveal the need to address the issue in a more spatially resolved manner, capable of uncovering diverse impacts across individual plants, river reaches and sub-basins. Results show that the use of coarse river network resolutions may lead to substantial overestimations in magnitude and length of impaired river reaches. Overall, there is a modest limitation on power production due to thermal pollution, given existing infrastructure, regulatory and climate conditions. However, tradeoffs between thermal pollution and electricity generation show important implications for the role of alternative cooling technologies and environmental regulation under current and future climates. Recirculating cooling technologies may nearly eliminate thermal pollution and improve power system reliability under stressed climate-water conditions. Regulatory limits also reduce thermal pollution, but at the expense of significant reductions in electricity generation capacity. However, results show several instances when power production capacity rises at individual plants when regulatory limits reduce upstream thermal pollution. These dynamics across energy-water systems highlight the need for high-resolution simulations and the value of coherent planning and optimization across infrastructure with mutual dependencies on natural resources to overcome climate-water constraints on productivity and bring to fruition energy and environmental win-win opportunities.

E3Net: a system for exploring E3-mediated regulatory networks of cellular functions.

PubMed

Han, Youngwoong; Lee, Hodong; Park, Jong C; Yi, Gwan-Su

2012-04-01

Ubiquitin-protein ligase (E3) is a key enzyme targeting specific substrates in diverse cellular processes for ubiquitination and degradation. The existing findings of substrate specificity of E3 are, however, scattered over a number of resources, making it difficult to study them together with an integrative view. Here we present E3Net, a web-based system that provides a comprehensive collection of available E3-substrate specificities and a systematic framework for the analysis of E3-mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms and 1671 E3-substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3-specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3-substrate networks and their correlated functions with graphical illustrations and summarized descriptions. As a result, E3Net provides a comprehensive resource of E3s, substrates, and their functional implications summarized from the regulatory network structures of E3-specific substrate groups and their correlated functions. This resource will facilitate further in-depth investigation of ubiquitination-dependent regulatory mechanisms. E3Net is freely available online at http://pnet.kaist.ac.kr/e3net.

The ascendance of microphysiological systems to solve the drug testing dilemma

PubMed Central

Dehne, Eva-Maria; Hasenberg, Tobias; Marx, Uwe

2017-01-01

The development of drugs is a process obstructed with manifold security and efficacy concerns. Although animal models are still widely used to meet the diligence required, they are regarded as outdated tools with limited predictability. Novel microphysiological systems intend to create systemic models of human biology. Their ability to host 3D organoid constructs in a controlled microenvironment with mechanical and electrophysiological stimuli enables them to create and maintain homeostasis. These platforms are, thus, envisioned to be superior tools for testing and developing substances such as drugs, cosmetics and chemicals. We will present reasons why microphysiological systems are required for the emerging demands, highlight current technological and regulatory obstacles, and depict possible solutions from state-of-the-art platforms from major contributors. PMID:28670475

The ascendance of microphysiological systems to solve the drug testing dilemma.

PubMed

Dehne, Eva-Maria; Hasenberg, Tobias; Marx, Uwe

2017-06-01

The development of drugs is a process obstructed with manifold security and efficacy concerns. Although animal models are still widely used to meet the diligence required, they are regarded as outdated tools with limited predictability. Novel microphysiological systems intend to create systemic models of human biology. Their ability to host 3D organoid constructs in a controlled microenvironment with mechanical and electrophysiological stimuli enables them to create and maintain homeostasis. These platforms are, thus, envisioned to be superior tools for testing and developing substances such as drugs, cosmetics and chemicals. We will present reasons why microphysiological systems are required for the emerging demands, highlight current technological and regulatory obstacles, and depict possible solutions from state-of-the-art platforms from major contributors.

Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities.

PubMed

Tan, Karin Y M; van der Beek, Eline M; Chan, M Y; Zhao, Xuejun; Stevenson, Leo

2015-09-01

The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The regulatory battleground: A briefing for commanders

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

Wirick, D.

1995-12-31

This imperfect analogy likens the history and current status of public utility regulation to a military campaign. Clearly, the relationship between regulators and utilities has not always been combative, but intermittent conflict has necessarily characterized the relationship. Nonetheless, this military analogy describes some of the elements of the history of regulation and may have implications for regulatory policy in the near term. The scene is a battlefield headquarters not far from the heat of the conflict. The commanders of regulatory units are gathered. In the distance, the low rumble of troop movements can be heard. Ladies and gentlemen, please takemore » your seats. As you are aware, recent developments have placed regulatory forces in extreme jeopardy. Our forces are under stress, and though they continue to fight, the confusion of the current situation is beginning to take its toll. In most cases, reinforcements have been denied and our lines of logistical support have been weakened. Without effective and rapid action on our part, the regulatory battle will be lost and we will be driven from the field. Until consumers are well-enough armed to protect themselves, a process that is certainly suspect and potentially time-consuming, they will be powerless and undoubtedly victimized.« less

Trajectories of regulatory behaviors in early infancy: Determinants of infant self-distraction and self-comforting.

PubMed

Planalp, Elizabeth M; Braungart-Rieker, Julia M

2015-03-01

The ability to effectively regulate emotions is an important marker for early socioemotional development. The uses of self-comforting behaviors and self-distraction have been empirically supported as effective regulatory strategies for infants, though research on determinants of such behaviors is scarce. Thus, a more thorough examination of the development of regulatory behaviors is needed. For the current study, 135 mothers, fathers, and their infants participated in laboratory visits at 3-, 5-, and 7-months of age where parent sensitivity and infant regulatory strategies were coded from the Still Face Paradigm. Parents also filled out questionnaires about infant temperament and parental involvement. Using multi-level modeling to examine levels and trajectories of self-comforting and self-distraction, the current study found: 1) infants higher in temperamental surgency used more self-distraction and self-comforting, 2) infants lower in surgency with highly involved parents increased in self-distraction at a faster rate, particularly with highly involved fathers, and 3) infants used self-comforting more than average with fathers when the infant was also lower in temperamental regulation. In addition, we examined trajectories of parent involvement and temperament in relation to infant regulatory strategy.

Section 210 of PURPA and solar-thermal-energy development: the current regulatory environment and suggestions for future action. Task III report

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

Not Available

Section 210 of the Public Utility Regulatory Policies Act of 1978 (PURPA) (16 U.S.C. Section 824a-3) (Attachment 1) was enacted to overcome certain institutional barriers and to provide a favorable, non-discriminatory regulatory environment for the integration of electricity-producing solar thermal and other qualifying technologies into the electric utility network. PURPA Section 210 is designed to reduce these institutional barriers for qualifying cogeneration and small power production facilities (QF's) - terminology which includes solar thermal facilities producing electricity for sale, if other prerequisites are met - by exempting certain QF's from economically burdensome legal requirements applicable to electric utilities, and bymore » requiring utilities to offer to purchase electricity from, and sell electricity to, QF's at reasonable and non-discriminatory rates. The present and future PURPA Section 210 regulatory implications for solar thermal QF's are explored. The current PURPA Section 210 regulatory environment and its consequences for solar thermal energy development are outlined. Legislation pending before Congress to amend PURPA Section 210 is described. Possible amendments to PURPA Section 210 that might further stimulate construction and operation of economically sound solar thermal facilities are explored.« less

Environmental impacts and regulatory policy implications of spray disposal of dredged material in Louisiana wetlands

USGS Publications Warehouse

Cahoon, D.R.; Cowan, J.H.

1988-01-01

The capabilities of a new wetland dredging technology were assessed along with associated newly developed state and federal regulatory policies to determine if policy expectations realistically match the technological achievement. Current regulatory practices require amelioration of spoil bank impacts upon abandonment of an oil/gas well, but this may not occur for many years or decades, if at all. Recently, a dreding method (high-pressure spray spoil disposal) was developed that does not create a spoil bank in the traditional sense. Its potential for reducing environmental impacts was recognized immediately by regulatory agencies for whom minimizing spoil bank impacts is a major concern. The use of high-pressure spray disposal as a suitable alternative to traditional dreding technology has been adopted as policy even though its value as a management tool has never been tested or verified. A qualitative evaluation at two spoil disposal sites in saline marsh indicates that high-pressure spray disposal may indeed have great potential to minimize impacts, but most of this potential remains unverified. Also, some aspects of current regulatory policy may be based on unrealistic expectations as to the ability of this new technology to minimize or eliminate spoil bank impacts.

Integrating novel data streams to support biosurveillance in commercial livestock production systems in developed countries: challenges and opportunities.

PubMed

Gates, M Carolyn; Holmstrom, Lindsey K; Biggers, Keith E; Beckham, Tammy R

2015-01-01

Reducing the burden of emerging and endemic infectious diseases on commercial livestock production systems will require the development of innovative technology platforms that enable information from diverse animal health resources to be collected, analyzed, and communicated in near real-time. In this paper, we review recent initiatives to leverage data routinely observed by farmers, production managers, veterinary practitioners, diagnostic laboratories, regulatory officials, and slaughterhouse inspectors for disease surveillance purposes. The most commonly identified challenges were (1) the lack of standardized systems for recording essential data elements within and between surveillance data streams, (2) the additional time required to collect data elements that are not routinely recorded by participants, (3) the concern over the sharing and use of business sensitive information with regulatory authorities and other data analysts, (4) the difficulty in developing sustainable incentives to maintain long-term program participation, and (5) the limitations in current methods for analyzing and reporting animal health information in a manner that facilitates actionable response. With the significant recent advances in information science, there are many opportunities to develop more sophisticated systems that meet national disease surveillance objectives, while still providing participants with valuable tools and feedback to manage routine animal health concerns.

In Vitro Exposure Systems and Dosimetry Assessment Tools ...

EPA Pesticide Factsheets

In 2009, the passing of The Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP) and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed “modified risk”. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference titled “In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products” to bring together stakeholders representing regulatory agencies, academia, and industry to address the research priorities articulated by the FDA CTP. Specific topics were covered to assess the status of current in vitro smoke and aerosol/vapor exposure systems, as well as the various approaches and challenges to quantifying the complex exposures, in in vitro pulmonary models developed for evaluating adverse pulmonary events resulting from tobacco product exposures. The four core topics covered were, 1) Tobacco Smoke And E-Cigarette Aerosols, 2) Air-Liquid Interface-In Vitro Exposure Systems, 3) Dosimetry Approaches For Particles And Vapors; In Vitro Dosimetry Determinations and 4) Exposure Microenvironment/Physiology Of Cells. The two and a half day workshop included presentations from 20 expert speakers, poster sessions, networking discussions, and breakout sessions which identified key findings and provided recommendations to advance these technologies. Here, we will re

Integrating Novel Data Streams to Support Biosurveillance in Commercial Livestock Production Systems in Developed Countries: Challenges and Opportunities

PubMed Central

Gates, M. Carolyn; Holmstrom, Lindsey K.; Biggers, Keith E.; Beckham, Tammy R.

2015-01-01

Reducing the burden of emerging and endemic infectious diseases on commercial livestock production systems will require the development of innovative technology platforms that enable information from diverse animal health resources to be collected, analyzed, and communicated in near real-time. In this paper, we review recent initiatives to leverage data routinely observed by farmers, production managers, veterinary practitioners, diagnostic laboratories, regulatory officials, and slaughterhouse inspectors for disease surveillance purposes. The most commonly identified challenges were (1) the lack of standardized systems for recording essential data elements within and between surveillance data streams, (2) the additional time required to collect data elements that are not routinely recorded by participants, (3) the concern over the sharing and use of business sensitive information with regulatory authorities and other data analysts, (4) the difficulty in developing sustainable incentives to maintain long-term program participation, and (5) the limitations in current methods for analyzing and reporting animal health information in a manner that facilitates actionable response. With the significant recent advances in information science, there are many opportunities to develop more sophisticated systems that meet national disease surveillance objectives, while still providing participants with valuable tools and feedback to manage routine animal health concerns. PMID:25973416

77 FR 56244 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

...-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of Proposed Amendments to the Real-Time Transaction Reporting System Information System and Subscription Service September 6.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the...

Single-Pass, Closed-System Rapid Expansion of Lymphocyte Cultures for Adoptive Cell Therapy

PubMed Central

Klapper, Jacob A.; Thomasian, Armen A.; Smith, Douglas M.; Gorgas, Gayle C.; Wunderlich, John R.; Smith, Franz O.; Hampson, Brian S.; Rosenberg, Steven A.; Dudley, Mark E.

2009-01-01

Adoptive cell therapy (ACT) for metastatic melanoma involves the ex vivo expansion and re-infusion of tumor infiltrating lymphocytes (TIL) obtained from resected specimens. With an overall objective response rate of fifty-six percent, this T-cell immunotherapy provides an appealing alternative to other therapies, including conventional therapies with lower response rates. However, there are significant regulatory and logistical concerns associated with the ex vivo activation and large scale expansion of these cells. The best current practice uses a rapid expansion protocol (REP) consisting of an ex vivo process that occurs in tissue culture flasks (T-flasks) and gas-permeable bags, utilizes OKT3 (anti-CD3 monoclonal antibody), recombinant human interleukin-2, and irradiated peripheral blood mononuclear cells to initiate rapid lymphocyte growth. A major limitation to the widespread delivery of therapy to large numbers of melanoma patients is the open system in which a REP is initiated. To address this problem, we have investigated the initiation, expansion and harvest at clinical scale of TIL in a closed-system continuous perfusion bioreactor. Each cell product met all safety criteria for patient treatment and by head-to-head comparison had a similar potency and phenotype as cells grown in control T-flasks and gas-permeable bags. However, the currently available bioreactor cassettes were limited in the total cell numbers that could be generated. This bioreactor may simplify the process of the rapid expansion of TIL under stringent regulatory conditions thereby enabling other institutions to pursue this form of ACT. PMID:19389403

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation.

PubMed

Pietrobon, Ricardo; Shah, Anand; Kuo, Paul; Harker, Matthew; McCready, Mariana; Butler, Christeen; Martins, Henrique; Moorman, C T; Jacobs, Danny O

2006-07-27

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process. The main objective of DSRC is to streamline regulatory research processes. The application was built using a combination of paper prototyping for system requirements and Java as the primary language for the application, in conjunction with the Model-View-Controller design model. The researcher interface was designed for simplicity so that it could be used by individuals with different computer literacy levels. Analogously, the administrator interface was designed with functionality as its primary goal. DSRC facilitates the exchange of regulatory documents between researchers and research administrators, allowing for tasks to be tracked and documents to be stored in a Web environment accessible from an Intranet. Usability was evaluated using formal usability tests and field observations. Formal usability results demonstrated that DSRC presented good speed, was easy to learn and use, had a functionality that was easily understandable, and a navigation that was intuitive. Additional features implemented upon request by initial users included: extensive variable categorization (in contrast with data capture using free text), searching capabilities to improve how research administrators could search an extensive number of researcher names, warning messages before critical tasks were performed (such as deleting a task), and confirmatory e-mails for critical tasks (such as completing a regulatory task). The current version of DSRC was shown to have excellent overall usability properties in handling research regulatory issues. It is hoped that its release as an open-source application will promote improved and streamlined regulatory processes for individual academic centers as well as larger research networks.

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

PubMed Central

Pietrobon, Ricardo; Shah, Anand; Kuo, Paul; Harker, Matthew; McCready, Mariana; Butler, Christeen; Martins, Henrique; Moorman, CT; Jacobs, Danny O

2006-01-01

Background Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process. Results The main objective of DSRC is to streamline regulatory research processes. The application was built using a combination of paper prototyping for system requirements and Java as the primary language for the application, in conjunction with the Model-View-Controller design model. The researcher interface was designed for simplicity so that it could be used by individuals with different computer literacy levels. Analogously, the administrator interface was designed with functionality as its primary goal. DSRC facilitates the exchange of regulatory documents between researchers and research administrators, allowing for tasks to be tracked and documents to be stored in a Web environment accessible from an Intranet. Usability was evaluated using formal usability tests and field observations. Formal usability results demonstrated that DSRC presented good speed, was easy to learn and use, had a functionality that was easily understandable, and a navigation that was intuitive. Additional features implemented upon request by initial users included: extensive variable categorization (in contrast with data capture using free text), searching capabilities to improve how research administrators could search an extensive number of researcher names, warning messages before critical tasks were performed (such as deleting a task), and confirmatory e-mails for critical tasks (such as completing a regulatory task). Conclusion The current version of DSRC was shown to have excellent overall usability properties in handling research regulatory issues. It is hoped that its release as an open-source application will promote improved and streamlined regulatory processes for individual academic centers as well as larger research networks. PMID:16872540

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

Selkirk, J.K.

The National Toxicology Program (NTP) was organized to support national public health programs by initiating research designed to understand the physiological, metabolic, and genetic basis for chemical toxicity. The primary mandated responsibilities of NTP were in vivo and vitro toxicity testing of potentially hazardous chemicals; broadening the spectrum of toxicological information on known hazardous chemicals; validating current toxicological assay systems as well as developing new and innovative toxicity testing technology; and rapidly communicating test results to government agencies with regulatory responsibilities and to the medical and scientific communities. 2 figs.

Structural and legal implications of e-health.

PubMed

Terry, N P

2000-01-01

Web and attendant e-Commerce phenomena are irretrievably at odds with the traditional structure and hence legal regulation of health delivery. E-Health delivers healthcare information, diagnosis, treatment, care, and prescribing of drugs in a nonlinear, nonhierarchical manner that encourages patients to "enter" the system at an infinite number of points, thus defying current regulatory constructs. Similarly, e-Commerce fundamentals such as disintermediation and disaggregation result in medical information being delivered through unfamiliar channels, creating immensely difficult questions for health lawyers.

MONOMIALS AND BASIN CYLINDERS FOR NETWORK DYNAMICS.

PubMed

Austin, Daniel; Dinwoodie, Ian H

We describe methods to identify cylinder sets inside a basin of attraction for Boolean dynamics of biological networks. Such sets are used for designing regulatory interventions that make the system evolve towards a chosen attractor, for example initiating apoptosis in a cancer cell. We describe two algebraic methods for identifying cylinders inside a basin of attraction, one based on the Groebner fan that finds monomials that define cylinders and the other on primary decomposition. Both methods are applied to current examples of gene networks.

MONOMIALS AND BASIN CYLINDERS FOR NETWORK DYNAMICS

PubMed Central

AUSTIN, DANIEL; DINWOODIE, IAN H

2014-01-01

We describe methods to identify cylinder sets inside a basin of attraction for Boolean dynamics of biological networks. Such sets are used for designing regulatory interventions that make the system evolve towards a chosen attractor, for example initiating apoptosis in a cancer cell. We describe two algebraic methods for identifying cylinders inside a basin of attraction, one based on the Groebner fan that finds monomials that define cylinders and the other on primary decomposition. Both methods are applied to current examples of gene networks. PMID:25620893

Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective.

PubMed

Tucker, Geoffrey; DeSilva, Binodh; Dressman, Jennifer; Ito, Michiho; Kumamoto, Takuya; Mager, Don; Mahler, Hanns-Christian; Maitland-van der Zee, Anke H; Pauletti, Giovanni M; Sasaki, Hitoshi; Shah, Vinod; Tang, Daniel; Ward, Michael

2016-09-01

The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science. Copyright © 2016. Published by Elsevier Inc.

Better Tests, Better Care: Improved Diagnostics for Infectious Diseases

PubMed Central

Caliendo, Angela M.; Gilbert, David N.; Ginocchio, Christine C.; Hanson, Kimberly E.; May, Larissa; Quinn, Thomas C.; Tenover, Fred C.; Alland, David; Blaschke, Anne J.; Bonomo, Robert A.; Carroll, Karen C.; Ferraro, Mary Jane; Hirschhorn, Lisa R.; Joseph, W. Patrick; Karchmer, Tobi; MacIntyre, Ann T.; Reller, L. Barth; Jackson, Audrey F.

2013-01-01

In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians. PMID:24200831

Mobile satellite regulation in the United States

NASA Technical Reports Server (NTRS)

Levin, Lon C.; Sonnenfeldt, Walter H.

1990-01-01

During the last decade, the U.S. FCC has developed the regulatory structure for the provision of mobile services via satellite. In May 1989, the FCC awarded American Mobile Satellite Corporation (AMSC) a license to provide the full range of domestic mobile satellite services in the U.S. At that time, the FCC reaffirmed the U.S. mobile satellite industry structure and spectrum allocations that had been adopted previously. Also in May 1989, the FCC authorized the Communications Satellite Corporation (COMSAT), the U.S. Signatory to Inmarsat, to provide international aeronautical satellite service via the Inmarsat system. Earlier in 1989, the FCC permitted the use of Ku-band satellites to provide messaging and tracking services. In the mid-1980's, the FCC established the Radiodetermination Satellite Service and awarded licenses. Among the mobile satellite matters currently facing the FCC are whether additional spectrum should be allocated for domestic 'generic' mobile satellite services, the regulatory structure for the provision of mobile satellite service on an interim basis before AMSC launches its dedicated satellites, and whether to authorize a low earth orbit satellite system to provide mobile data service.

Geographic variations in anthropogenic drivers that influence the vulnerability and resilience of social-ecological systems.

PubMed

Forbes, Bruce C; Fresco, Nancy; Shvidenko, Anatoly; Danell, Kjell; Chapin, F Stuart

2004-08-01

Across the circumpolar North large disparities in the distribution of renewable and nonrenewable resources, human population density, capital investments, and basic residential and transportation infrastructure combine to create recognizable hotspots of recent and foreseeable change. Northern Fennoscandia exemplifies a relatively benign situation due to its current economic and political stability. Northern Russia is experiencing rapid, mostly negative changes reflecting the general state of crisis since the collapse of the Soviet Union. North America enjoys a relatively stable regulatory structure to mitigate environmental degradation associated with industry, but is on the verge of approving massive new development schemes that would significantly expand the spatial extent of potentially affected social-ecological systems. Institutional or regulatory context influences the extent to which ecosystem services are buffered against environmental change. With or without a warming climate, certain geographic areas appear especially vulnerable to damages that may threaten their ability to supply goods and services in the near future. Climate change may exacerbate this situation in some places but may offer opportunities to enhance resilience in the long term.

Monitoring substrate enables real-time regulation of a protein localization pathway.

PubMed

Ito, Koreaki; Mori, Hiroyuki; Chiba, Shinobu

2018-06-01

Protein localization machinery supports cell survival and physiology, suggesting the potential importance of its expression regulation. Here, we summarize a remarkable scheme of regulation, which allows real-time feedback regulation of the machinery expression. A class of regulatory nascent polypeptides, called monitoring substrates, undergoes force-sensitive translation arrest. The resulting ribosome stalling on the mRNA then affects mRNA folding to expose the ribosome-binding site of the downstream target gene and upregulate its translation. The target gene encodes a component of the localization machinery, whose physical action against the monitoring substrate leads to arrest cancellation. Thus, this scheme of feedback loop allows the cell to adjust the amount of the machinery to correlate inversely with the effectiveness of the process at a given moment. The system appears to have emerged late in evolution, in which a narrow range of organisms selected a distinct monitoring substrate-machinery combination. Currently, regulatory systems of SecM-SecA, VemP-SecDF2 and MifM-YidC2 are known to occur in different bacterial species.

CO2Explorer: Conducting Greenhouse-Gas Measurements of Landfills using a Small Fixed-wing UAV

NASA Astrophysics Data System (ADS)

Hollingsworth, Peter; Allen, Grant; Kabbabe, Khristopher; Pitt, Joseph

2017-04-01

Quantifying inventories of Greenhouse gas emissions, primarily Methane and Carbon Dioxide, from distributed sources such as a landfill has historically been undertaken using one of several ground based measurement techniques. These methods are either time and/or resource intensive. As a result regulatory agencies have started looking at the potential of using small-unmanned aircraft to supplement or supplant the current methods. The challenge of using a UAV to perform these tasks is the trade-off between accuracy, operational flexibility and operational productivity. This is driven by the state-of-the-art in measurement instruments, the operating environment at landfills and the regulatory/safety environment surrounding UAV operations. This work describes the development of the operational concept, and associated UAV measurement platform for the CO2Explorer. It looks at the scientific, engineering and possible policy trades and compares the use of small rotary and fixed-wing UAVs from both an operational and measurement perspective. This work also makes recommendations on system development and operation for users lacking in both systems engineering and operational experience.

Treatment of Depression From a Self-Regulation Perspective: Basic Concepts and Applied Strategies in Self-System Therapy.

PubMed

Strauman, Timothy J; Eddington, Kari M

2017-02-01

Self-regulation models of psychopathology provide a theory-based, empirically supported framework for developing psychotherapeutic interventions that complement and extend current cognitive-behavioral models. However, many clinicians are only minimally familiar with the psychology of self-regulation. The aim of the present manuscript is twofold. First, we provide an overview of self-regulation as a motivational process essential to well-being and introduce two related theories of self-regulation which have been applied to depression. Second, we describe how self-regulatory concepts and processes from those two theories have been translated into psychosocial interventions, focusing specifically on self-system therapy (SST), a brief structured treatment for depression that targets personal goal pursuit. Two randomized controlled trials have shown that SST is superior to cognitive therapy for depressed clients with specific self-regulatory deficits, and both studies found evidence that SST works in part by restoring adaptive self-regulation. Self-regulation-based psychotherapeutic approaches to depression hold significant promise for enhancing treatment efficacy and ultimately may provide an individualizable framework for treatment planning.

Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Nebraska. Preliminary background report

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

Feurer, D A; Weaver, C L; Gallagher, K C

1980-01-01

The state agency with principal authority to regulate electric public utilities is the Power Review Board (Board). However, the Board in fact, exercised little regulatory authority over heat and power utilities because all electrical power in Nebraska is currently supplied by public authorities and is not subject to regulation by the Board. Gas and water utilities are also subject to general supervision by municipalities. The Board is compised of five members - an attorney, an engineer, one accountant, two lay - persons appointed by the governor and confirmed by the legislature. All members are appointed to overlapping four-year terms, andmore » none may serve more than two consecutive terms. Decisions by the Board require the approval of a majority of its members. The Public Service Commission of Nebraska is a constitutionally created body. Its powers and duties include the regulation of rates, service, and general control of common carriers as the legislature may provide by law. Other state agencies also possess limited regulatory jurisdiction which may be relevant to an energy facility. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.« less

Low-income minority fathers' control strategies and children's regulatory skills

PubMed Central

Malin, Jenessa L.; Cabrera, Natasha J.; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith

2015-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24-months and children's regulatory skills at pre-kindergarten (pre-K). Using a sample of low-income minority families with 2-year-olds from the Early Head Start Evaluation Research Program (n = 71) we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24-months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at pre-kindergarten. There were three main findings. First, fathers' overwhelmingly use commands (e.g., do that) to promote compliance in their 24-month old children. Second, children's vocabulary skills predict fathers' regulatory behaviors during a father-child interaction, whereas children's gender predicts fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24-months predict children's sustained attention at pre-kindergarten whereas fathers' regulatory language at 24-months predicts children's emotion regulation at pre-kindergarten. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. PMID:25798496

Low-income, minority fathers' control strategies and their children's regulatory skills.

PubMed

Malin, Jenessa L; Cabrera, Natasha J; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith L

2014-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24 months, and children's regulatory skills at prekindergarten (pre-K). Using a sample of low-income, minority families with 2-year-olds from the Early Head Start Research and Evaluation Project (n = 71), we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24 months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at prekindergarten. There were three main findings. First, fathers overwhelmingly used commands (e.g., "Do that.") to promote compliance in their 24-month-old children. Second, children's vocabulary skills predicted fathers' regulatory behaviors during a father-child interaction whereas children's gender predicted fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24 months predicted children's sustained attention at pre-K whereas fathers' regulatory language at 24 months predicted children's emotion regulation at pre-K. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. © 2014 Michigan Association for Infant Mental Health.

COUNCIL FOR REGULATORY ENVIRONMENTAL MODELING (CREM) PILOT WATER QUALITY MODEL SELECTION TOOL

EPA Science Inventory

EPA's Council for Regulatory Environmental Modeling (CREM) is currently supporting the development of a pilot model selection tool that is intended to help the states and the regions implement the total maximum daily load (TMDL) program. This tool will be implemented within the ...

77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... year, FDA speakers provide updates on current efforts affecting the development of global regulatory strategies, while industry professionals from some of today's leading pharmaceutical companies present case... hear directly from FDA experts and representatives of global regulatory authorities on best practices...

Issues in mass spectrometry between bench chemists and regulatory laboratory managers

USDA-ARS?s Scientific Manuscript database

At the 123rd AOAC Annual Meeting in Philadelphia, 45 residue chemists gathered for a roundtable discussion of mass spectrometry (MS) for regulatory purposes involving chemical residues analysis. The session was conceived to address current technical and communication issues about MS between “bench ...

Resolving the problem of compliance with the ever increasing and changing regulations

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

Leigh, H.

1991-06-01

The most common problem identified at several US Department of Energy (DOE) sites is regulatory compliance. Simply, the project viability depends on identifying regulatory requirements at the beginning of a specific project to avoid possible delays and cost overruns. The Radioisotope Power Systems Facility (RFSP) is using the Regulatory Compliance System (RCS) to deal with the problem that well over 1000 regulatory documents had to be reviewed for possible compliance requirements applicable to the facility. This overwhelming number of possible documents is not atypical of all DOE facilities thus far reviewed using the RCS system. The RCS was developed tomore » provide a control and tracking of all the regulatory and institutional requirements on a given project. WASTREN, Inc., developed the RCS through various DOE contracts and continues to enhance and update the system for existing and new contracts. The RCS provides the information to allow the technical expert to assimilate and manage accurate resource information, compile the checklists, and document that the project or facility fulfills all of the appropriate regulatory requirements. The RCS provides on-line information, including status throughput the project life, thereby allowing more intelligent and proactive decision making. Also, consistency and traceability are provided for regulatory compliance documentation. 1 ref., 1 fig.« less

[Current situation of and the political measures for drug abuse/dependence].

PubMed

Wada, Kiyoshi; Ozaki, Shigeru; Kondo, Ayumi

2008-04-01

More than 10 years has passed since 1995 when the third epidemic of methamphetamine abuse started in Japan. We are now still in the third epidemic of methamphetamine abuse, thought the current situation of drug abuse/dependence has obviously changed from previously. Considering several kinds of nationwide surveys and censuses, the authors summarized the change as follows: a) obvious decrease in solvent abuse/dependence, b) stabilization of methamphetamine abuse/dependence, c) increase in abuse of such drugs as cannabis or MDMA which don't have high potential to cause drug-induced psychosis, and d) emergence of non-regulatory drugs represented by designer drugs. These imply the change a) from "hard drugs" to "soft drugs", b) from Japanese unique situation which is symbolized by solvent abuse to Western situation which is symbolized by cannabis abuse, and c) from "illicit drugs" to "non-regulatory drugs". These characteristics reveal that there is the limitation to the Japanese Government policy which has tried to control the drug issue mainly as criminal cases for many years and that it is time now to change its policy. The authors stress the necessities of development of medical treatment targeting drug dependence and of its social support system.

"Smart pharmacy" master blends integrated supply chains with patient care to uphold regulatory compliances.

PubMed

Bhinder, Prabhjot; Oberoi, Mandeep Singh

2009-01-01

Hospitals require better information connectivity because timing and content of the information to be traded is critical. The imperative success in the past has generated renewed thrust on the expectations and credibility of the current enterprise resource planning (ERP) applications in health care. The desire to bring improved connectivity and to match it with critical timing remains the penultimate dream. Currently, majority of ERP system integrators are not able to match these requirements of the healthcare industry. It is perceived that the concept of ERP has made the process of segregating bills and patient records much easier. Hence the industry is able to save more lives, but at the cost of an individual's privacy as it enables to access the database of patients and medical histories through the common database shared by hospitals though at a quicker rate. Businesses such as health care providers, pharmaceutical manufacturers, and distributors have already implemented rapid ERPs. The new concept "Smart Pharmacies" will link the process all the way from drug delivery, patient care, demand management, drug repository, and pharmaceutical manufacturers while maintaining Regulatory Compliances and make the vital connections where these Businesses will talk to each other electronically.

The potential of the second sight system bionic eye implant for partial sight restoration.

PubMed

Luo, Yvonne Hsu-Lin; Fukushige, Eka; Da Cruz, Lyndon

2016-07-01

Second Sight System bionic eye implant, a commercially available visual prosthesis developed by Second Sight Medical Products, has been implanted in over 125 patients with outer retinal dystrophies such as retinitis pigmentosa. The system has gained regulatory approval in both the USA and Europe, and aims to restore vision by electrical stimulation of the nerve cells of the inner retina. In this review, we present the safety profile of this implant from the international clinical trial and discuss the nature and levels of improvement in visual function achieved by patients implanted with the system. Expert commentary: Future developments for the system will be explored following the discussion of the current usefulness of the device, its limitation as and the areas in which further development is necessary.

[Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison].

PubMed

Kuhlmann-Gottke, Johanna; Duchow, Karin

2015-11-01

At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.

Transdermal patches: history, development and pharmacology.

PubMed

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-05-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. © 2015 The British Pharmacological Society.

US definitions, current use, and FDA stance on use of platelet-rich plasma in sports medicine.

PubMed

Beitzel, Knut; Allen, Donald; Apostolakos, John; Russell, Ryan P; McCarthy, Mary Beth; Gallo, Gregory J; Cote, Mark P; Mazzocca, Augustus D

2015-02-01

With increased utilization of platelet-rich plasma (PRP), it is important for clinicians to understand the United States, the Food and Drug Administration (FDA) regulatory role and stance on PRP. Blood products such as PRP fall under the prevue of FDA's Center for Biologics Evaluation and Research (CBER). CBER is responsible for regulating human cells, tissues, and cellular and tissue-based products. The regulatory process for these products is described in the FDA's 21 CFR 1271 of the Code of Regulations. Under these regulations, certain products including blood products such as PRP are exempt and therefore do not follow the FDA's traditional regulatory pathway that includes animal studies and clinical trials. The 510(k) application is the pathway used to bring PRP preparation systems to the market. The 510(k) application allows devices that are "substantially equivalent" to a currently marketed device to come to the market. There are numerous PRP preparation systems on the market today with FDA clearance; however, nearly all of these systems have 510(k) clearance for producing platelet-rich preparations intended to be used to mix with bone graft materials to enhance bone graft handling properties in orthopedic practices. The use of PRP outside this setting, for example, an office injection, would be considered "off label." Clinicians are free to use a product off-label as long as certain responsibilities are met. Per CBER, when the intent is the practice of medicine, clinicians "have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product's use and effects." Finally, despite PRP being exempted, the language in 21 CFR 1271 has caused some recent concern over activated PRP; however to date, the FDA has not attempted to regulate activated PRP. Clinicians using activated PRP should be mindful of these concerns and continued to stay informed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges.

PubMed

Jossen, Valentin; van den Bos, Christian; Eibl, Regine; Eibl, Dieter

2018-05-01

Human mesenchymal stem cell (hMSC)-based therapies are of increasing interest in the field of regenerative medicine. As economic considerations have shown, allogeneic therapy seems to be the most cost-effective method. Standardized procedures based on instrumented single-use bioreactors have been shown to provide billion of cells with consistent product quality and to be superior to traditional expansions in planar cultivation systems. Furthermore, under consideration of the complex nature and requirements of allogeneic hMSC-therapeutics, a new equipment for downstream processing (DSP) was successfully evaluated. This mini-review summarizes both the current state of the hMSC production process and the challenges which have to be taken into account when efficiently producing hMSCs for the clinical scale. Special emphasis is placed on the upstream processing (USP) and DSP operations which cover expansion, harvesting, detachment, separation, washing and concentration steps, and the regulatory demands.

Vaccines in Argentina: a regulatory view.

PubMed

Pérez, A C; Diez, R A

2003-07-28

In Argentina, vaccines for immuno-preventable diseases are regulated by the national regulatory agency, the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (the National Administration of Drugs, Food and Medical Devices, or ANMAT) created in 1992 to ensure efficacy and safety of drugs, food and medical devices available in the country, according to Law 16,463 and Decree 150/92. ANMAT has licensed 84 out of 157 vaccines registered in Argentina. Since 1994, ANMAT evaluated, approved and inspected 20 clinical trials with vaccines (1.8% of the 1062 trials approved by the agency since that time). The National System of Pharmaco-vigilance has received 318 communications of eventual adverse post-vaccination events (0.3% of the total). In addition, ANMAT provides support to the National Immunisation Programme. The current procedure is to follow international guidelines in the field, to be prepared for new, rapidly changing scenarios.

Risk Analysis as Regulatory Science: Toward The Establishment of Standards

PubMed Central

Murakami, Michio

2016-01-01

Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional ‘Standard I’, which has a paternalistic orientation, and ‘Standard II’, established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being. PMID:27475751

Nuclear Forensic Science: Analysis of Nuclear Material Out of Regulatory Control

DOE PAGES

Kristo, Michael J.; Gaffney, Amy M.; Marks, Naomi; ...

2016-05-11

Nuclear forensic science seeks to identify the origin of nuclear materials found outside regulatory control. It is increasingly recognized as an integral part of a robust nuclear security program. Our review highlights areas of active, evolving research in nuclear forensics, with a focus on analytical techniques commonly employed in Earth and planetary sciences. Applications of nuclear forensics to uranium ore concentrates (UOCs) are discussed first. UOCs have become an attractive target for nuclear forensic researchers because of the richness in impurities compared to materials produced later in the fuel cycle. Furthermore, the development of chronometric methods for age dating nuclearmore » materials is then discussed, with an emphasis on improvements in accuracy that have been gained from measurements of multiple radioisotopic systems. Finally, papers that report on casework are reviewed, to provide a window into current scientific practice.« less

Risk Analysis as Regulatory Science: Toward The Establishment of Standards.

PubMed

Murakami, Michio

2016-09-01

Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional 'Standard I', which has a paternalistic orientation, and 'Standard II', established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being. © The Author 2016. Published by Oxford University Press.

A PerR-like protein involved in response to oxidative stress in the extreme bacterium Deinococcus radiodurans

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

Liu, Chengzhi; Wang, Liangyan; Li, Tao

2014-07-18

Highlights: • We report a novel PerR-like protein of Fur family in D. radiodurans that is not annotated in the current database. • drperR responses to H{sub 2}O{sub 2} and functions as a negative regulator of katE and dps. • We provided implications on how to utilize sequenced genome data and the importance of genome data mining. • This study adds knowledge to complicated regulatory network that responds to ROS stress in D. radiodurans. - Abstract: Response and defense systems against reactive oxygen species (ROS) contribute to the remarkable resistance of Deinococcus radiodurans to oxidative stress induced by oxidants ormore » radiation. However, mechanisms involved in ROS response and defense systems of D. radiodurans are not well understood. Fur family proteins are important in ROS response. Only a single Fur homolog is predicted by sequence similarity in the current D. radiodurans genome database. Our bioinformatics analysis demonstrated an additional guanine nucleotide in the genome of D. radiodurans that is not in the database, leading to the discovery of another Fur homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to hydrogen peroxide (H{sub 2}O{sub 2}) and increased catalase activity in cell extracts. Real-time PCR results indicated that DrPerR functions as a repressor of the catalase gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved cells) gene under H{sub 2}O{sub 2} stress by DrPerR point to its regulatory role in metal ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is involved in ROS response and defense. These results help clarify the complicated regulatory network that responds to ROS stress in D. radiodurans.« less

78 FR 803 - Revisions to Electric Reliability Organization Definition of Bulk Electric System and Rules of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

...In this Final Rule, pursuant to section 215 of the Federal Power Act, the Federal Energy Regulatory Commission (Commission) approves modifications to the currently-effective definition of ``bulk electric system'' developed by the North American Electric Reliability Corporation (NERC), the Commission-certified Electric Reliability Organization. The Commission finds that the modified definition of ``bulk electric system'' removes language allowing for regional discretion in the currently-effective bulk electric system definition and establishes a bright-line threshold that includes all facilities operated at or above 100 kV. The modified definition also identifies specific categories of facilities and configurations as inclusions and exclusions to provide clarity in the definition of ``bulk electric system.'' In this Final Rule, the Commission also approves: NERC's revisions to its Rules of Procedure, which create an exception process to add elements to, or remove elements from, the definition of ``bulk electric system'' on a case-by-case basis; NERC's form entitled ``Detailed Information To Support an Exception Request'' that entities will use to support requests for exception from the ``bulk electric system'' definition; and NERC's implementation plan for the revised ``bulk electric system'' definition.

48 CFR 2001.301 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 2001.301 Section 2001.301 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Agency Acquisition Regulations 2001.301 Policy. Policy...

48 CFR 2001.301 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 2001.301 Section 2001.301 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Agency Acquisition Regulations 2001.301 Policy. Policy...

48 CFR 2001.301 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. 2001.301 Section 2001.301 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Agency Acquisition Regulations 2001.301 Policy. Policy...

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces.

PubMed

Lu, Fengjuan; Hou, Yanyan; Zhang, Heming; Chu, Yiwen; Xia, Haiyang; Tian, Yongqiang

2017-08-01

The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators. The study of regulatory genes that influence antibiotic biosynthesis in Streptomyces spp. not only provides a theoretical basis for antibiotic biosynthesis in Streptomyces but also helps to increase the yield of antibiotics via molecular manipulation of these regulatory genes. Currently, more and more emphasis is being placed on the regulatory genes of antibiotic biosynthetic gene clusters in Streptomyces spp., and many studies on these genes have been performed to improve the yield of antibiotics in Streptomyces. This paper lists many antibiotic biosynthesis regulatory genes in Streptomyces spp. and focuses on frequently investigated regulatory genes that are involved in pathway-specific regulation and pleiotropic regulation and their applications in genetic engineering.

77 FR 7613 - Dow Chemical Company; Dow Chemical TRIGA Research Reactor; Facility Operating License No. R-108

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-264; NRC-2012-0026] Dow Chemical Company; Dow Chemical TRIGA Research Reactor; Facility Operating License No. R-108 AGENCY: Nuclear Regulatory Commission... Facility Operating License No. R-108 (``Application''), which currently authorizes the Dow Chemical Company...

78 FR 49563 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... futures on all of the volatility indexes that underlie volatility index options trading on CBOE. Currently, volatility index (security) futures expirations correspond to each volatility index options expiration months...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed Rule To Amend Rule...

76 FR 30605 - Assessment and Collection of Regulatory Fees For Fiscal Year 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... the Wireless Telecommunications Bureau's Numbering Resource Utilization Forecast and Annual CMRS... compute their fee payment using the standard methodology \\32\\ that is currently in place for CMRS Wireless... Commission, Regulatory Fees Fact Sheet: What You Owe--Commercial Wireless Services for FY 2010 at 1 (released...

75 FR 39603 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

..., Commission, from Liz Heese, Managing Director, Issuer Services, Pink OTC Markets, Inc. (``Pink OTC''), dated January 20, 2010 (``Pink OTC Letter''), and Letter to Elizabeth M. Murphy, Secretary, Commission, from...'') market. FINRA currently operates the OTC Bulletin Board (``OTCBB''), which provides a mechanism for FINRA...

75 FR 41262 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... striking and ranking the arbitrators on the lists. Currently, FINRA sends the parties lists of available... arbitrators from the parties' ranking lists. However, after each side exercises its strikes, typically only... arbitrators during the ranking and striking stage of the arbitrator appointment process. In instances where...

76 FR 50741 - 2011 Parenteral Drug Association/Food and Drug Administration Joint Public Conference; Quality...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-16

... Compliance in Today's Regulatory Enforcement Environment AGENCY: Food and Drug Administration, HHS. ACTION... Regulatory Enforcement Environment.'' The conference will span 2\\1/2\\ days and cover current issues affecting... facilitate the development and continuous improvement of safe and effective medical products. The conference...

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…

76 FR 31271 - Public Meeting: Preliminary Regulatory Determinations for the Third Contaminant Candidate List...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... Regulatory Determinations for the Third Contaminant Candidate List (CCL 3) AGENCY: Environmental Protection... require the EPA to determine every five years, whether to regulate at least five contaminants from the current Contaminant Candidate List (CCL) with a national primary drinking water regulation. The process of...

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 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

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.

[Research on problem of exogenous pollution of Chinese medicine resources from perspective of circular economy].

PubMed

Yang, Yi; Tian, Kan; Tian, Hong

2016-08-01

Based on the in-depth analysis of the current situation of the exogenous pollution of Chinese medicine resources, this research mainly discusses the intrinsic link and practical significance between the development of circular economy in Chinese medicine resources and the control of the problem of the exogenous pollution from the perspective of circular economy, and proposes some suggestions to develop the recycling economy of Chinese medicine resources from the establishment of legal system, mechanism of development, production norms, industry standards and regulatory system of the recycling of Chinese medicine resources. Copyright© by the Chinese Pharmaceutical Association.

76 FR 38119 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

.../ Regulatory Information Number (RIN) and title, by any of the following methods: * Federal Rulemaking Portal... System Name: Human Research Protection Program (HRPP) Records (September 11, 2008, 73 FR 52838). Changes: * * * * * System Name: Delete entry and replace with ``Research Regulatory Oversight Records.'' System location...

Perspective for the development of companion diagnostics and regulatory landscape to encourage personalized medicine in Japan.

PubMed

Tazawa, Yoshiaki

2016-01-01

On July 1st, 2013, the Ministry of Health, Labor and Welfare (MHLW) issued an official notification regarding the co-development of companion diagnostics (CDx) with a drug which requires any exclusive diagnostic test or medical device to predict efficacy or adverse reactions to the drug. The main frame and contents in the MHLW's notification are quite similar to the summaries in the final guidance issued by the US Food and Drug Administration (FDA) on August 6th, 2014 Guidance for Industry and Food and Drug Administration Staff (In Vitro Companion Diagnostic Devices, [2014] ), and these recommend industries to develop, study and submit CDx and the corresponding drug contemporaneously as much as possible. Following the MHLW's notification, the Pharmaceutical and Medical Device Agency (PMDA) notified on December 26th, 2013, "the technical guidance for co-development of CDx and the drug" that mentioned the regulatory requirements for clinical trial of the drug and CDx as well as analytical validity of CDx required for the trials. These official notifications from the Ministry and the Agency may be useful for pharmaceutical and diagnostics makers to understand how they should co-develop and validate CDx for clinical trials and regulatory submission. However, since the most anticipated technologies such as the next generation sequencer (NGS) are more complex and its medical risks could be high level, the existing regulatory system focusing on only diagnostics reagents and devices that are developed and manufactured by in vitro diagnostics (IVD) makers may be no longer suitable for the characteristics of CDx for the future.As an increase of clinical needs for multiple biomarkers assay by DNA sequencer, on November 19th, 2013, the FDA cleared 510 K for NGS and its universal kit. On October 3rd, 2014, moreover, the agency notified two drafts of guidance (Anticipated Details of the Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratory in Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), [2014]; Anticipated Details of the Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratory in FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDT), [2014]) for oversight of laboratory developed tests (LDTs) with medium or high medical risks. These FDA's strategic decisions and new regulatory frameworks may allow the clinical laboratories to develop and perform more easily NGS-based CDx under the certification of Clinical Laboratory Improvement Amendments (CLIA). However, neither law nor regulated quality management system similar to the CLIA exists in Japan. To effectively validate LDTs and NGS for medical practice, Japan should learn more the current regulatory changes and initiatives in the US, as well as to reform the regulatory frameworks and create any regulated quality management system for clinical laboratory testing to be reimbursed.

Bite the apple, get driven out of the garden: A risky story telling at the ASME town meeting

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

Majumdar, K.C.

1994-11-01

Risk, the all-encompassing four-letter word became a widely used household cliche and an institutional mantra in the nineties. Risk analysis models from the Garden of Eden to the Capitol Hill lawn have made a number of sharp paradigm shifts to evolve itself as a decision-making tool from individual risk perception to societal risk-based regulatory media. Risk always coexists with benefit and is arbitrated by costs. Risk-benefit analysis has been in use in business and industry in economic ventures for a long time. Only recently risk management in its current state of development, evolved as a regulatory tool for controlling largemore » technological systems that have potential impacts on the health and safety of the public and on the sustainability of the ecology and the environment. This paper summarizes the evolution of the risk management concepts and models in industry and the regulatory agencies in the US over the last three decades. It also discusses the benefits and limitations of this evolving discipline as it is applied to high-risk technologies from the nuclear power plant and petrochemical industry, etc. to nuclear weapons technology.« less

The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network.

PubMed

Radeck, Jara; Fritz, Georg; Mascher, Thorsten

2017-02-01

The cell envelope stress response (CESR) encompasses all regulatory events that enable a cell to protect the integrity of its envelope, an essential structure of any bacterial cell. The underlying signaling network is particularly well understood in the Gram-positive model organism Bacillus subtilis. It consists of a number of two-component systems (2CS) and extracytoplasmic function σ factors that together regulate the production of both specific resistance determinants and general mechanisms to protect the envelope against antimicrobial peptides targeting the biogenesis of the cell wall. Here, we summarize the current picture of the B. subtilis CESR network, from the initial identification of the corresponding signaling devices to unraveling their interdependence and the underlying regulatory hierarchy within the network. In the course of detailed mechanistic studies, a number of novel signaling features could be described for the 2CSs involved in mediating CESR. This includes a novel class of so-called intramembrane-sensing histidine kinases (IM-HKs), which-instead of acting as stress sensors themselves-are activated via interprotein signal transfer. Some of these IM-HKs are involved in sensing the flux of antibiotic resistance transporters, a unique mechanism of responding to extracellular antibiotic challenge.

21 CFR 26.6 - Equivalence assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS... draft programs for assessing the equivalence of the respective regulatory systems in terms of quality... inspection reports), joint training, and joint inspections for the purpose of assessing regulatory systems...

Heterogeneous but “Standard” Coding Systems for Adverse Events: Issues in Achieving Interoperability between Apples and Oranges

PubMed Central

Richesson, Rachel L.; Fung, Kin Wah; Krischer, Jeffrey P.

2008-01-01

Monitoring adverse events (AEs) is an important part of clinical research and a crucial target for data standards. The representation of adverse events themselves requires the use of controlled vocabularies with thousands of needed clinical concepts. Several data standards for adverse events currently exist, each with a strong user base. The structure and features of these current adverse event data standards (including terminologies and classifications) are different, so comparisons and evaluations are not straightforward, nor are strategies for their harmonization. Three different data standards - the Medical Dictionary for Regulatory Activities (MedDRA) and the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) terminologies, and Common Terminology Criteria for Adverse Events (CTCAE) classification - are explored as candidate representations for AEs. This paper describes the structural features of each coding system, their content and relationship to the Unified Medical Language System (UMLS), and unsettled issues for future interoperability of these standards. PMID:18406213

Current challenges in bioequivalence, quality, and novel assessment technologies for topical products.

PubMed

Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D; Benfeldt, Eva; Davit, Barbara; Ganes, Derek; Ghosh, Tapash; Kanfer, Isadore; Kasting, Gerald B; Katz, Lindsey; Lionberger, Robert; Lu, Guang Wei; Maibach, Howard I; Pershing, Lynn K; Rackley, Russell J; Raw, Andre; Shukla, Chinmay G; Thakker, Kailas; Wagner, Nathalie; Zovko, Elizabeta; Lane, Majella E

2014-04-01

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed. The outcome of the workshop emphasized both a need for greater attention to quality, possibly, via a Quality-By-Design (QBD) approach and a need to develop a "whole toolkit" approach towards the problem of determination of rate and extent in the assessment of topical bioavailability. The discussion on the BE and clinical equivalence of topical products revealed considerable concerns about the variability present in the current methodologies utilized by the industry and regulatory agencies. It was proposed that academicians, researchers, the pharmaceutical industry and regulators work together to evaluate and validate alternative methods that are based on both the underlying science and are adapted to the drug product itself instead of single "universal" method.

48 CFR 41.402 - Rate changes and regulatory intervention.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regulatory intervention. 41.402 Section 41.402 Federal Acquisition Regulations System FEDERAL ACQUISITION... changes and regulatory intervention. (a) When a change is proposed to rates or terms and conditions of... that may be of interest to other Federal agencies, and intervention before a regulatory body is...

48 CFR 41.402 - Rate changes and regulatory intervention.

Code of Federal Regulations, 2010 CFR

2010-10-01

... regulatory intervention. 41.402 Section 41.402 Federal Acquisition Regulations System FEDERAL ACQUISITION... changes and regulatory intervention. (a) When a change is proposed to rates or terms and conditions of... that may be of interest to other Federal agencies, and intervention before a regulatory body is...

48 CFR 41.402 - Rate changes and regulatory intervention.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regulatory intervention. 41.402 Section 41.402 Federal Acquisition Regulations System FEDERAL ACQUISITION... changes and regulatory intervention. (a) When a change is proposed to rates or terms and conditions of... that may be of interest to other Federal agencies, and intervention before a regulatory body is...

48 CFR 41.402 - Rate changes and regulatory intervention.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regulatory intervention. 41.402 Section 41.402 Federal Acquisition Regulations System FEDERAL ACQUISITION... changes and regulatory intervention. (a) When a change is proposed to rates or terms and conditions of... that may be of interest to other Federal agencies, and intervention before a regulatory body is...

48 CFR 41.402 - Rate changes and regulatory intervention.

Code of Federal Regulations, 2011 CFR

2011-10-01

... regulatory intervention. 41.402 Section 41.402 Federal Acquisition Regulations System FEDERAL ACQUISITION... changes and regulatory intervention. (a) When a change is proposed to rates or terms and conditions of... that may be of interest to other Federal agencies, and intervention before a regulatory body is...

Pharmaceutical company perspectives on current safety risk communications in Japan.

PubMed

Urushihara, Hisashi; Kobashi, Gen; Masuda, Hideaki; Taneichi, Setsuko; Yamamoto, Michiko; Nakayama, Takeo; Kawakami, Koji; Matsuda, Tsutomu; Ohta, Kaori; Sugimori, Hiroki

2014-01-01

In 1987, a group infection of hepatitis in patients receiving a contaminated fibrinogen product was first reported to the Japanese regulatory agency. Eventually, this serious drug incident involved more than 10,000 cases of infection. In response, the Government of Japan established a responding inspection committee in 2008 to make recommendations for the restructuring of drug regulatory administration. The final report was issued in 2010. One agenda item of this restructuring was the improvement of drug-related safety risk communications. Our research group on drug safety risk communications, which is funded by the Government of Japan, surveyed pharmaceutical companies regarding their perspective on current risk communications. The survey was conducted using an anonymous questionnaire developed for this study which included the three operational domains of targets, contents, and measures of drug risk communication. Fifty-two of the 74 member companies of the Post-marketing Surveillance Subcommittee of the Japan Pharmaceutical Manufacturer's Association participated, and this response rate of more than 70% was considered sufficient to ensure the external validity of the survey results. Results showed that the most highly prioritized aspect of risk messaging was the strength of evidence, and that outcome evaluation of risk communication gained recognition. Further, while physicians and pharmacists were the most prioritized communication targets, pharmacovigilance departments devoted the most resources to regulators, at more than 30%. The Internet was recognized as a useful public source of risk information, whereas Drug Guides for Patients delivered on the web were considered under-recognized. Further discussion of these results with the aim of enhancing the restructuring of the Japanese drug regulatory administration system are warranted.

Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

PubMed

Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

2015-01-01

At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.

PubMed

Verbeken, Gilbert; Pirnay, Jean-Paul; De Vos, Daniel; Jennes, Serge; Zizi, Martin; Lavigne, Rob; Casteels, Minne; Huys, Isabelle

2012-06-01

For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

Management of solid waste

NASA Astrophysics Data System (ADS)

Thompson, W. T.; Stinton, L. H.

1980-04-01

Compliance with the latest regulatory requirements addressing disposal of radioactive, hazardous, and sanitary solid waste criteria in the selection, design, and operation of solid waste management facilities. Due to the state of flux of these regulatory requirements from EPA and NRC, several waste management options were of solid waste. The current regulatory constraints and the design and operational requirements for construction of both storage and disposal facilities for use in management of DOE-ORO solid waste are highlighted. Capital operational costs are included for both disposal and storage options.

Changes in glycolytic enzyme activities in aging erythrocytes fractionated by counter-current distribution in aqueous polymer two-phase systems.

PubMed Central

Jimeno, P; Garcia-Perez, A I; Luque, J; Pinilla, M

1991-01-01

Human and rat erythrocytes were fractionated by counter-current distribution in charge-sensitive dextran/poly(ethylene glycol) two-phase systems. The specific activities of the key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase) declined along the distribution profiles, although the relative positions of the activity profiles were reversed in the two species. These enzymes maintained their normal response to specific regulatory effectors in all cell fractions. No variations were observed for phosphoglycerate kinase and bisphosphoglycerate mutase activities. Some correlations between enzyme activities (pyruvate kinase/hexokinase, pyruvate kinase/phosphofructokinase, pyruvate kinase/pyruvate kinase plus phosphoglycerate kinase, pyruvate kinase/bisphosphoglycerate mutase and phosphoglycerate kinase/bisphosphoglycerate mutase ratios) were studied in whole erythrocyte populations as well as in cell fractions. These results strongly support the fractionation of human erythrocytes according to cell age, as occurs with rat erythrocytes. PMID:1656939

Quality management for the international transport of laboratory animals.

PubMed

Leary, Steven L

2008-01-01

Increased collaboration between investigators at different institutions has increased the number of laboratory animals being transported. The current system of laws and regulations governing animal shipments is inconsistent and government agencies often have areas of overlapping regulatory management. Furthermore, the lack of industry-wide shipping standards and good practices contributes to confusion among those responsible for shipment. One answer to these quality control issues would be the establishment of independent, industry-regulated 'good practices' for animal transport, similar to those used in laboratories for experimental design. These good practices could be based on the existing International Air Transport Association Live Animals Regulations, with contributions from representatives of the specialties involved. Additionally, quality control under the current system of patchwork regulations could be improved if each institution, both academic and commercial, would designate a single point of contact to follow each shipment from start to finish.

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.

An update of the federal drinking water regs

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

Pontius, F.W.

1995-02-01

Previous reviews have summarized the regulations promulgated for volatile organic chemicals (VOCs), fluoride, surface water treatment, total coliform bacteria, lead and copper, and Phase 2 and Phase 5 synthetic organic contaminants (SOCs) and inorganic contaminants (IOCs). Current developments related to these rules and anticipated new rules are reviewed in this article. Current numerical drinking water standards and best available technology (BAT) are summarized. The status of all current, proposed, and anticipated regulations is also summarized. Dates for anticipated agency actions are based on the US Environmental Protection Agency's (USEPA's) published regulatory agenda and on information released by the agency throughmore » December 1994; these dates can change as the agency reconsiders its regulatory policies.« less

Health and safety implications of occupational exposure to engineered nanomaterials.

PubMed

Stebounova, Larissa V; Morgan, Hallie; Grassian, Vicki H; Brenner, Sara

2012-01-01

The rapid growth and commercialization of nanotechnology are currently outpacing health and safety recommendations for engineered nanomaterials. As the production and use of nanomaterials increase, so does the possibility that there will be exposure of workers and the public to these materials. This review provides a summary of current research and regulatory efforts related to occupational exposure and medical surveillance for the nanotechnology workforce, focusing on the most prevalent industrial nanomaterials currently moving through the research, development, and manufacturing pipelines. Their applications and usage precedes a discussion of occupational health and safety efforts, including exposure assessment, occupational health surveillance, and regulatory considerations for these nanomaterials. Copyright © 2011 Wiley Periodicals, Inc.

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.

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 mission of public health protection has remained a constant feature over the years; and (iii) since the 1970s other factors such as public health promotion, international harmonization, innovation, and agency modernization are playing more important role in regulatory agency thinking and actions.

Combined heat and power systems: economic and policy barriers to growth.

PubMed

Kalam, Adil; King, Abigail; Moret, Ellen; Weerasinghe, Upekha

2012-04-23

Combined Heat and Power (CHP) systems can provide a range of benefits to users with regards to efficiency, reliability, costs and environmental impact. Furthermore, increasing the amount of electricity generated by CHP systems in the United States has been identified as having significant potential for impressive economic and environmental outcomes on a national scale. Given the benefits from increasing the adoption of CHP technologies, there is value in improving our understanding of how desired increases in CHP adoption can be best achieved. These obstacles are currently understood to stem from regulatory as well as economic and technological barriers. In our research, we answer the following questions: Given the current policy and economic environment facing the CHP industry, what changes need to take place in this space in order for CHP systems to be competitive in the energy market? We focus our analysis primarily on Combined Heat and Power Systems that use natural gas turbines. Our analysis takes a two-pronged approach. We first conduct a statistical analysis of the impact of state policies on increases in electricity generated from CHP system. Second, we conduct a Cost-Benefit analysis to determine in which circumstances funding incentives are necessary to make CHP technologies cost-competitive. Our policy analysis shows that regulatory improvements do not explain the growth in adoption of CHP technologies but hold the potential to encourage increases in electricity generated from CHP system in small-scale applications. Our Cost-Benefit analysis shows that CHP systems are only cost competitive in large-scale applications and that funding incentives would be necessary to make CHP technology cost-competitive in small-scale applications. From the synthesis of these analyses we conclude that because large-scale applications of natural gas turbines are already cost-competitive, policy initiatives aimed at a CHP market dominated primarily by large-scale (and therefore already cost-competitive) systems have not been effectively directed. Our recommendation is that for CHP technologies using natural gas turbines, policy focuses should be on increasing CHP growth in small-scale systems. This result can be best achieved through redirection of state and federal incentives, research and development, adoption of smart grid technology, and outreach and education.

Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

PubMed

Gazestani, Vahid H; Salavati, Reza

2015-01-01

Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

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

Current approaches and future role of high content imaging in safety sciences and drug discovery.

PubMed

van Vliet, Erwin; Daneshian, Mardas; Beilmann, Mario; Davies, Anthony; Fava, Eugenio; Fleck, Roland; Julé, Yvon; Kansy, Manfred; Kustermann, Stefan; Macko, Peter; Mundy, William R; Roth, Adrian; Shah, Imran; Uteng, Marianne; van de Water, Bob; Hartung, Thomas; Leist, Marcel

2014-01-01

High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore, high content imaging is considered a promising technology to address the challenges for the "Toxicity testing in the 21st century" approach. Currently, high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging in academia, pharmaceutical industry and regulatory bodies with the objective to compile the state-of-the-art of the technology in the different institutions. Together they defined technical and methodological gaps, proposed quality control measures and performance standards, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.

48 CFR 2001.402 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. 2001.402 Section 2001.402 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.402 Policy. (a...

48 CFR 2001.402 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 2001.402 Section 2001.402 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.402 Policy. (a...

48 CFR 2001.402 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 2001.402 Section 2001.402 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.402 Policy. (a...

75 FR 27768 - Current Connection, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

..., Motions To Intervene, and Competing Applications May 11, 2010. On March 30, 2010, Current Connection, LLC.... Applicant Contact: Timothy D. Smith, CEO, Current Connection, LLC, 1300 Rankin Drive, Troy, MI 48083; phone... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13694-000] Current...

Scientific misconduct, the pharmaceutical industry, and the tragedy of institutions.

PubMed

Cohen-Kohler, Jillian Clare; Esmail, Laura C

2007-09-01

This paper examines how current legislative and regulatory models do not adequately govern the pharmaceutical industry towards ethical scientific conduct. In the context of a highly profit-driven industry, governments need to ensure ethical and legal standards are not only in place for companies but that they are enforceable. We demonstrate with examples from both industrialized and developing countries how without sufficient controls, there is a risk that corporate behaviour will transgress ethical boundaries. We submit that there is a critical need for urgent drug regulatory reform. There must be robust regulatory structures in place which enforce corporate governance mechanisms to ensure that pharmaceutical companies maintain ethical standards in drug research and development and the marketing of pharmaceuticals. What is also needed is for the pharmaceutical industry to adopt authentic "corporate social responsibility" policies as current policies and practices are insufficient.

77 FR 21557 - System Energy Resources, Inc.; Notice of Petition for Declaratory Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-52-000] System Energy Resources, Inc.; Notice of Petition for Declaratory Order Take notice that on March 28, 2012, System Energy Resources, Inc. (System Energy Resources), submitted a petition requesting the Federal Energy Regulatory...

Innovations in Technology for the Treatment of Diabetes: Clinical Development of the Artificial Pancreas (an Autonomous System)

PubMed Central

Klonoff, David C; Zimliki, Charles L; Stevens, LCDR Alan; Beaston, Patricia; Pinkos, Arleen; Choe, Sally Y; Arreaza-Rubín, Guillermo; Heetderks, William

2011-01-01

The Food and Drug Administration in collaboration with the National Institutes of Health presented a public workshop to facilitate medical device innovation in the development of the artificial pancreas (or autonomous system) for the treatment of diabetes mellitus on November 10, 2010 in Gaithersburg, Maryland. The purpose of the workshop was to discuss four aspects of artificial pancreas research and development, including: (1) the current state of device systems for autonomous systems for the treatment of diabetes mellitus; (2) challenges in developing this expert device system using existing technology; (3) clinical expectations for these systems; and (4) development plans for the transition of this device system toward an outpatient setting. The patients discussed how clinical science, system components, and regulatory policies will all need to harmonize in order to achieve the goal of seeing an AP product brought forward to the marketplace for patients to use. PMID:21722597