Regulatory Compliance in Multi-Tier Supplier Networks

NASA Technical Reports Server (NTRS)

Goossen, Emray R.; Buster, Duke A.

2014-01-01

Over the years, avionics systems have increased in complexity to the point where 1st tier suppliers to an aircraft OEM find it financially beneficial to outsource designs of subsystems to 2nd tier and at times to 3rd tier suppliers. Combined with challenging schedule and budgetary pressures, the environment in which safety-critical systems are being developed introduces new hurdles for regulatory agencies and industry. This new environment of both complex systems and tiered development has raised concerns in the ability of the designers to ensure safety considerations are fully addressed throughout the tier levels. This has also raised questions about the sufficiency of current regulatory guidance to ensure: proper flow down of safety awareness, avionics application understanding at the lower tiers, OEM and 1st tier oversight practices, and capabilities of lower tier suppliers. Therefore, NASA established a research project to address Regulatory Compliance in a Multi-tier Supplier Network. This research was divided into three major study efforts: 1. Describe Modern Multi-tier Avionics Development 2. Identify Current Issues in Achieving Safety and Regulatory Compliance 3. Short-term/Long-term Recommendations Toward Higher Assurance Confidence This report presents our findings of the risks, weaknesses, and our recommendations. It also includes a collection of industry-identified risks, an assessment of guideline weaknesses related to multi-tier development of complex avionics systems, and a postulation of potential modifications to guidelines to close the identified risks and weaknesses.

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.

On the Path to SunShot. Utility Regulatory and Business Model Reforms for Addressing the Financial Impacts of Distributed Solar on Utilities

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

Barbose, Galen; Miller, John; Sigrin, Ben

Net-energy metering (NEM) has helped drive the rapid growth of distributed PV (DPV) but has raised concerns about electricity cost shifts, utility financial losses, and inefficient resource allocation. These concerns have motivated real and proposed reforms to utility regulatory and business models. This report explores the challenges and opportunities associated with such reforms in the context of the U.S. Department of Energy's SunShot Initiative. Most of the reforms to date address NEM concerns by reducing the benefits provided to DPV customers and thus constraining DPV deployment. Eliminating NEM nationwide, by compensating exports of PV electricity at wholesale rather than retailmore » rates, could cut cumulative DPV deployment by 20% in 2050 compared with a continuation of current policies. This would slow the PV cost reductions that arise from larger scale and market certainty. It could also thwart achievement of the SunShot deployment goals even if the initiative's cost targets are achieved. This undesirable prospect is stimulating the development of alternative reform strategies that address concerns about distributed PV compensation without inordinately harming PV economics and growth. These alternatives fall into the categories of facilitating higher-value DPV deployment, broadening customer access to solar, and aligning utility profits and earnings with DPV. Specific strategies include utility ownership and financing of DPV, community solar, distribution network operators, services-driven utilities, performance-based incentives, enhanced utility system planning, pricing structures that incentivize high-value DPV configurations, and decoupling and other ratemaking reforms that reduce regulatory lag. These approaches represent near- and long-term solutions for preserving the legacy of the SunShot Initiative.« less

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.

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.

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.

A global regulatory science agenda for vaccines.

PubMed

Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

2013-04-18

The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

Addressing unwarranted clinical variation: A rapid review of current evidence.

PubMed

Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

2018-05-15

Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and

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.

On the Path to SunShot - Utility Regulatory Business Model Reforms forAddressing the Financial Impacts of Distributed Solar on Utilities

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

None, None

Net-energy metering (NEM) with volumetric retail electricity pricing has enabled rapid proliferation of distributed photovoltaics (DPV) in the United States. However, this transformation is raising concerns about the potential for higher electricity rates and cost-shifting to non-solar customers, reduced utility shareholder profitability, reduced utility earnings opportunities, and inefficient resource allocation. Although DPV deployment in most utility territories remains too low to produce significant impacts, these concerns have motivated real and proposed reforms to utility regulatory and business models, with profound implications for future DPV deployment. This report explores the challenges and opportunities associated with such reforms in the context ofmore » the U.S. Department of Energy’s SunShot Initiative. As such, the report focuses on a subset of a broader range of reforms underway in the electric utility sector. Drawing on original analysis and existing literature, we analyze the significance of DPV’s financial impacts on utilities and non-solar ratepayers under current NEM rules and rate designs, the projected effects of proposed NEM and rate reforms on DPV deployment, and alternative reforms that could address utility and ratepayer concerns while supporting continued DPV growth. We categorize reforms into one or more of four conceptual strategies. Understanding how specific reforms map onto these general strategies can help decision makers identify and prioritize options for addressing specific DPV concerns that balance stakeholder interests.« less

17 CFR 3.30 - Current address for purpose of delivery of communications from the Commission or the National...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Current address for purpose of... Current address for purpose of delivery of communications from the Commission or the National Futures Association. (a) The address of each registrant, applicant for registration and principal, as submitted on the...

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 ...

In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market

PubMed Central

Geris, L.; Guyot, Y.; Schrooten, J.; Papantoniou, I.

2016-01-01

The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design. PMID:27051516

In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market.

PubMed

Geris, L; Guyot, Y; Schrooten, J; Papantoniou, I

2016-04-06

The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design.

An electronic regulatory document management system for a clinical trial network.

PubMed

Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko

2010-01-01

A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.

18 CFR 376.203 - Mailing address of Commission during emergency conditions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REVISED GENERAL RULES ORGANIZATION, MISSION... § 376.203 Mailing address of Commission during emergency conditions. The Chairman may direct that during... Commission shall be addressed to the Federal Energy Regulatory Commission, Official Mail and Messenger...

Nanomedicines: addressing the scientific and regulatory gap.

PubMed

Tinkle, Sally; McNeil, Scott E; Mühlebach, Stefan; Bawa, Raj; Borchard, Gerrit; Barenholz, Yechezkel Chezy; Tamarkin, Lawrence; Desai, Neil

2014-04-01

Nanomedicine is the application of nanotechnology to the discipline of medicine: the use of nanoscale materials for the diagnosis, monitoring, control, prevention, and treatment of disease. Nanomedicine holds tremendous promise to revolutionize medicine across disciplines and specialties, but this promise has yet to be fully realized. Beyond the typical complications associated with drug development, the fundamentally different and novel physical and chemical properties of some nanomaterials compared to materials on a larger scale (i.e., their bulk counterparts) can create a unique set of opportunities as well as safety concerns, which have only begun to be explored. As the research community continues to investigate nanomedicines, their efficacy, and the associated safety issues, it is critical to work to close the scientific and regulatory gaps to assure that nanomedicine drives the next generation of biomedical innovation. © 2014 New York Academy of Sciences.

Current status of herbal product: Regulatory overview

PubMed Central

Sharma, Sanjay

2015-01-01

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

Current status of herbal product: Regulatory overview.

PubMed

Sharma, Sanjay

2015-01-01

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

A Regulatory Framework for Nanotechnology

DTIC Science & Technology

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

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...

Genomics in the land of regulatory science.

PubMed

Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

2015-06-01

Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making. Published by Elsevier Inc.

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.

Preclinical assessment of abuse liability of biologics: In defense of current regulatory control policies.

PubMed

Gauvin, David V; Zimmermann, Zachary J; Baird, Theodore J

2015-10-01

Current regulatory policies of both the US Food and Drug Administration and Drug Enforcement Administration do not delineate automatic exceptions for biologics with respect to preclinical assessments for abuse liability of all new entities. As defined in current guidance documents and drug control policies, an exception may be given upon thorough review of available data, therapeutic target and in consultation with the Controlled Substances Staff within the Center for Drug Evaluation and Research of the FDA, but a blanket exception for all biological entities is not currently available. We review the abuse liability testing of four known biologics with definitive positive abuse liability signals in the three core abuse liability assays, self-administration, drug discrimination, and dependence potential described in the FDA draft guidance document. Interestingly, while all four examplars have positive abuse liability signals in all three assays, two of these biologics are controlled under the Comprehensive Drug Abuse and Control Act (CSA, 1970) and the other two are not currently controlled. Admittedly, these four biologics are small molecule entities. However, there is no reference to "molecular size" in the legally-binding statutory definition of biologics under the FD&C act or in the Controlled Substances Act. Neither of these drug control policy mandates have a bifurcated control status in which to make exceptions based solely on molecular size. With the current pharmaceutical focus on new technologies, such as "Trojan Horses", targeting the active transport of large molecule entities directly into the CNS, an argument to automatically exempt new molecular entities solely on molecular size is untenable. We argue that for the safety and health of general public the current regulatory control status be maintained until definitive criteria for exceptions can be identified and amended to both the FD&CA and CSA, if warranted. Copyright © 2015 Elsevier Inc. All

Air Emissions Damages from Municipal Drinking Water Treatment Under Current and Proposed Regulatory Standards.

PubMed

Gingerich, Daniel B; Mauter, Meagan S

2017-09-19

Water treatment processes present intersectoral and cross-media risk trade-offs that are not presently considered in Safe Drinking Water Act regulatory analyses. This paper develops a method for assessing the air emission implications of common municipal water treatment processes used to comply with recently promulgated and proposed regulatory standards, including concentration limits for, lead and copper, disinfection byproducts, chromium(VI), strontium, and PFOA/PFOS. Life-cycle models of electricity and chemical consumption for individual drinking water unit processes are used to estimate embedded NO x , SO 2 , PM 2.5 , and CO 2 emissions on a cubic meter basis. We estimate air emission damages from currently installed treatment processes at U.S. drinking water facilities to be on the order of $500 million USD annually. Fully complying with six promulgated and proposed rules would increase baseline air emission damages by approximately 50%, with three-quarters of these damages originating from chemical manufacturing. Despite the magnitude of these air emission damages, the net benefit of currently implemented rules remains positive. For some proposed rules, however, the promise of net benefits remains contingent on technology choice.

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.

Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

PubMed

Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

2018-02-17

Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism." © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

10 CFR 590.104 - Address for filing documents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Address for filing documents. 590.104 Section 590.104 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS General Provisions § 590.104 Address for...

10 CFR 590.104 - Address for filing documents.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Address for filing documents. 590.104 Section 590.104 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS General Provisions § 590.104 Address for...

47 CFR 101.1309 - Regulatory status.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Regulatory status. 101.1309 Section 101.1309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1309 Regulatory status. (a) The Commission will...

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

Nanomaterials in Food - Current and Future Applications and Regulatory Aspects

NASA Astrophysics Data System (ADS)

Aschberger, K.; Gottardo, S.; Amenta, V.; Arena, M.; Botelho Moniz, F.; Bouwmeester, H.; Brandhoff, P.; Mech, A.; Quiros Pesudo, L.; Rauscher, H.; Schoonjans, R.; Vittoria Vettori, M.; Peters, R.

2015-05-01

Nanotechnology can contribute to the development of innovative applications in the agriculture, food and feed sector by e.g. enabling improved delivery of nutrients or increased efficacy of agrichemicals. It is expected that applications will increase in the near future and may therefore become a relevant source of human exposure to nanomaterials (NM). To gain more up-to date information, RIKILT and the Joint Research Centre (JRC) were commissioned by the European Food Safety Authority (EFSA) to prepare an inventory of currently used and reasonably foreseen applications of NM in agriculture and food/feed production and carried out a review of regulatory aspects concerning NM in both EU and non-EU countries. An analysis of the information records in the inventory shows that nano-encapsulates, silver and titanium dioxide are the most frequent type of NM listed and that food additives and food contact materials are the most frequent types of application. A comparison between marketed applications and those in development indicates a trend from inorganic materials (e.g. silver) towards organic materials (nano-encapsulates, nanocomposites). Applications in novel food, feed additives, biocides and pesticides are currently mostly at a developmental stage. The review of EU and non-EU legislation shows that currently a few EU legal acts incorporate a definition of a nanomaterial and specific provisions for NM, whereas in many non-EU countries a broader approach is applied, which mainly builds on guidance for industry.

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.

Research on Current Water Systems and Regulatory Support

EPA Science Inventory

This project will supply research results to support federal regulations and guidance. It will also provide strategies to regions, states, and communities for improved regulatory compliance and rapid and effective emergency response where appropriate (e.g. harmful algal bloom out...

Select Biosolids Regulatory Processes

EPA Pesticide Factsheets

Historical Regulatory Development and activities EPA has undertaken to respond to statutory obligations, respond to the National Academy of Sciences, understand pollutants that may occur in sewage sludge, and address dioxins in sewage sludge.

A prior-based integrative framework for functional transcriptional regulatory network inference

PubMed Central

Siahpirani, Alireza F.

2017-01-01

Abstract Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization. PMID:27794550

Behavioral Economic Laboratory Research in Tobacco Regulatory Science.

PubMed

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

2016-10-01

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

Therapeutic gene editing: delivery and regulatory perspectives.

PubMed

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-06-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues.

Therapeutic gene editing: delivery and regulatory perspectives

PubMed Central

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-01-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues. PMID:28392568

Rationales for regulatory activity

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

Perhac, R.M.

1997-02-01

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

Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology

PubMed Central

Chappell, James; Jensen, Kirsten; Freemont, Paul S.

2013-01-01

A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology. PMID:23371936

77 FR 8072 - Semiannual Regulatory Flexibility Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... six months. ADDRESSES: Comments should be addressed to Jennifer J. Johnson, Secretary of the Board... Regulatory and Deregulatory Actions, which is coordinated by the Office of Management and Budget under... pledged; and certain other elements including a strategic analysis of the company's plans for maintaining...

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

PubMed Central

Nakayama, Yoshikazu; Aruga, Atsushi

2015-01-01

Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

Unique Regulatory Approach for Licensing the Port Hope Remediation Project in Canada - 13315

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

Kostova, M.; Howard, D.; Elder, P.

2013-07-01

The Port Hope remediation project is a part of a larger initiative of the Canadian Federal Government the Port Hope Area Initiative (PHAI) which is based upon a community proposal. The Government of Canada, through Natural Resources Canada (NRCan) is investing $1.28 billion over 10 years to clean up historic low-level radioactive waste in the Port Hope Area and to provide long-term safe management of the low-level radioactive wastes in the Port Hope Area. These wastes arose from the activities of a former Federal Crown Corporation (Eldorado Nuclear) and its private sector predecessors. In Canada, historic waste are defined asmore » low-level radioactive waste that was managed in a manner no longer considered acceptable, but for which the original producer cannot reasonably be held responsible or no longer exists and for which the Federal Government has accepted responsibility. In Canada, under the current regulatory framework, the environmental remediation is not considered as a distinct phase of the nuclear cycle. The regulatory approach for dealing with existing sites contaminated with radioactive residues is defined on the basis of risk and application of existing regulations. A unique regulatory approach was taken by the Canadian Nuclear Safety Commission (CNSC) to address the various licensing issues and to set out the requirements for licensing of the Port Hope Project within the current regulatory framework. (authors)« less

Water Systems Project 1: Current Systems and Regulatory Support

EPA Science Inventory

Water Systems Project 1 objectives: 1) Supply research results to support federal regulations and guidance; 2) provide strategies to regions, states, and communities for improved regulatory compliance, and 3) provide rapid and effective emergency response where appropriate (e.g. ...

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...

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

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

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

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

Addressing the unequal geographic distribution of specialist doctors in indonesia: the role of the private sector and effectiveness of current regulations.

PubMed

Meliala, Andreasta; Hort, Krishna; Trisnantoro, Laksono

2013-04-01

As in many countries, the geographic distribution of the health workforce in Indonesia is unequal, with a concentration in urban and more developed areas, and a scarcity in rural and remote areas. There is less information on the distribution of specialist doctors, yet inequalities in their distribution could compromise efforts to achieve universal coverage by 2014. This paper uses data from 2007 and 2008 to describe the geographic distribution of specialist doctors in Indonesia, and to examine two key factors that influence the distribution and are targets of current policies: sources of income for specialist doctors, and specialist doctor engagement in private practice. The data demonstrates large differences in the ratio of specialist doctors to population among the provinces of Indonesia, with higher ratios on the provinces of the islands of Java, and much lower ratios on the more remote provinces in eastern Indonesia. Between 65% and 80% of specialist doctors' income derives from private practice in non-state hospitals or private clinics. Despite regulations limiting practice locations to three, most specialists studied in a provincial capital city were working in more than three locations, with some working in up to 7 locations, and spending only a few hours per week in their government hospital practice. Our study demonstrates that the current regulatory policies and financial incentives have not been effective in addressing the maldistribution of specialist doctors in a context of a growing private sector and predominance of doctors' income from private sources. A broader and more integrated policy approach, including more innovative service delivery strategies for rural and remote areas, is recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

PubMed

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

Computational architecture of the yeast regulatory network

NASA Astrophysics Data System (ADS)

Maslov, Sergei; Sneppen, Kim

2005-12-01

The topology of regulatory networks contains clues to their overall design principles and evolutionary history. We find that while in- and out-degrees of a given protein in the regulatory network are not correlated with each other, there exists a strong negative correlation between the out-degree of a regulatory protein and in-degrees of its targets. Such correlation positions large regulatory modules on the periphery of the network and makes them rather well separated from each other. We also address the question of relative importance of different classes of proteins quantified by the lethality of null-mutants lacking one of them as well as by the level of their evolutionary conservation. It was found that in the yeast regulatory network highly connected proteins are in fact less important than their low-connected counterparts.

Functional Evolution of a cis-Regulatory Module

PubMed Central

Palsson, Arnar; Alekseeva, Elena; Bergman, Casey M; Nathan, Janaki; Kreitman, Martin

2005-01-01

Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules. PMID:15757364

In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses

PubMed Central

2015-01-01

Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards

In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses.

PubMed

Becerra-Fajardo, Laura; Ivorra, Antoni

2015-01-01

Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards

Sex differences in regulatory cells in experimental stroke.

PubMed

Seifert, Hilary A; Benedek, Gil; Liang, Jian; Nguyen, Ha; Kent, Gail; Vandenbark, Arthur A; Saugstad, Julie A; Offner, Halina

2017-08-01

Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19 + CD5 + CD1d hi B10 cells as well as anti-inflammatory CD11b + CD206 + microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60min middle cerebral artery occlusion followed by 96h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

Methods for Addressing Technology-induced Errors: The Current State.

PubMed

Borycki, E; Dexheimer, J W; Hullin Lucay Cossio, C; Gong, Y; Jensen, S; Kaipio, J; Kennebeck, S; Kirkendall, E; Kushniruk, A W; Kuziemsky, C; Marcilly, R; Röhrig, R; Saranto, K; Senathirajah, Y; Weber, J; Takeda, H

2016-11-10

The objectives of this paper are to review and discuss the methods that are being used internationally to report on, mitigate, and eliminate technology-induced errors. The IMIA Working Group for Health Informatics for Patient Safety worked together to review and synthesize some of the main methods and approaches associated with technology- induced error reporting, reduction, and mitigation. The work involved a review of the evidence-based literature as well as guideline publications specific to health informatics. The paper presents a rich overview of current approaches, issues, and methods associated with: (1) safe HIT design, (2) safe HIT implementation, (3) reporting on technology-induced errors, (4) technology-induced error analysis, and (5) health information technology (HIT) risk management. The work is based on research from around the world. Internationally, researchers have been developing methods that can be used to identify, report on, mitigate, and eliminate technology-induced errors. Although there remain issues and challenges associated with the methodologies, they have been shown to improve the quality and safety of HIT. Since the first publications documenting technology-induced errors in healthcare in 2005, we have seen in a short 10 years researchers develop ways of identifying and addressing these types of errors. We have also seen organizations begin to use these approaches. Knowledge has been translated into practice in a short ten years whereas the norm for other research areas is of 20 years.

Methods for Addressing Technology-Induced Errors: The Current State

PubMed Central

Dexheimer, J. W.; Hullin Lucay Cossio, C.; Gong, Y.; Jensen, S.; Kaipio, J.; Kennebeck, S.; Kirkendall, E.; Kushniruk, A. W.; Kuziemsky, C.; Marcilly, R.; Röhrig, R.; Saranto, K.; Senathirajah, Y.; Weber, J.; Takeda, H.

2016-01-01

Summary Objectives The objectives of this paper are to review and discuss the methods that are being used internationally to report on, mitigate, and eliminate technology-induced errors. Methods The IMIA Working Group for Health Informatics for Patient Safety worked together to review and synthesize some of the main methods and approaches associated with technology-induced error reporting, reduction, and mitigation. The work involved a review of the evidence-based literature as well as guideline publications specific to health informatics. Results The paper presents a rich overview of current approaches, issues, and methods associated with: (1) safe HIT design, (2) safe HIT implementation, (3) reporting on technology-induced errors, (4) technology-induced error analysis, and (5) health information technology (HIT) risk management. The work is based on research from around the world. Conclusions Internationally, researchers have been developing methods that can be used to identify, report on, mitigate, and eliminate technology-induced errors. Although there remain issues and challenges associated with the methodologies, they have been shown to improve the quality and safety of HIT. Since the first publications documenting technology-induced errors in healthcare in 2005, we have seen in a short 10 years researchers develop ways of identifying and addressing these types of errors. We have also seen organizations begin to use these approaches. Knowledge has been translated into practice in a short ten years whereas the norm for other research areas is of 20 years. PMID:27830228

Addressing Circuitous Currents MVDC Power Systems Protection

DTIC Science & Technology

2017-12-31

load . The converter modules are current-controlled buck converters. They are being controlled to provide a no - load voltage of 155V at their outputs...PAGE Form Approved 0MB No . 0704-0188 The public reporting burden for this collection of information is estimated to average 1 hour per response...distribution is unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The work investigates Z-source breakers in multi-zone systems with current to the load through

76 FR 42074 - Consideration of Rulemaking To Address Prompt Remediation of Residual Radioactivity During...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-18

... Address Prompt Remediation of Residual Radioactivity During Operations AGENCY: Nuclear Regulatory... States, and other stakeholders on a potential rulemaking to address prompt remediation of residual... DPR does not have a mandatory requirement for licensees to conduct radiological remediation during...

EPA Leadership on Science, Innovation, and Decision Support Tools for Addressing Current and Future Challenges.

PubMed

Hecht, Alan D; Ferster, Aaron; Summers, Kevin

2017-10-16

When the U.S. Environmental Protection Agency (EPA) was established nearly 50 years ago, the nation faced serious threats to its air, land, and water, which in turn impacted human health. These threats were effectively addressed by the creation of EPA (in 1970) and many subsequent landmark environmental legislations which in turn significantly reduced threats to the Nation's environment and public health. A key element of historic legislation is research aimed at dealing with current and future problems. Today we face national and global challenges that go beyond classic media-specific (air, land, water) environmental legislation and require an integrated paradigm of action and engagement based on (1) innovation based on science and technology, (2) stakeholder engagement and collaboration, and (3) public education and support. This three-pronged approach recognizes that current environmental problems, include social as well as physical and environmental factors, are best addressed through collaborative problem solving, the application of innovation in science and technology, and multiple stakeholder engagement. To achieve that goal, EPA's Office of Research and Development (ORD) is working directly with states and local communities to develop and apply a suite of accessible decision support tools (DST) that aim to improve environmental conditions, protect human health, enhance economic opportunity, and advance a resilient and sustainability society. This paper showcases joint EPA and state actions to develop tools and approaches that not only meet current environmental and public health challenges, but do so in a way that advances sustainable, healthy, and resilient communities well into the future. EPA's future plans should build on current work but aim to effectively respond to growing external pressures. Growing pressures from megatrends are a major challenge for the new Administration and for cities and states across the country. The recent hurricanes hitting

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

Regulatory system reform of occupational health and safety in China.

PubMed

Wu, Fenghong; Chi, Yan

2015-01-01

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

Regulatory Aspects Of Implementing Electrokinetic Remediation

EPA Science Inventory

A better understanding of the environmental impact of hazardous waste management practices has led to new environmental laws and a comprehensive regulatory program. This program is designed to address remediation of past waste management practices and to ensure that the hazardou...

The role of business in addressing the long-term implications of the current food crisis.

PubMed

Yach, Derek

2008-12-05

Before the onset of the current food crisis, the evidence of a severely neglected nutrition crisis was starting to receive attention. Increased food prices are having severe impacts on the nutritional status of populations. Our current food system has evolved over decades in a largely unplanned manner and without consideration for the complexity and implications of linkages between health, nutrition, agricultural, economic, trade and security issues. The underlying causes for the nutrition crisis include the above, as well as decades of neglect with regard to nutrition, and agricultural science (especially in emerging markets); a failure of governance with respect to the major players involved in nutrition, a weak response by government donors and Foundations to invest in basic nutrition (in contrast to growing support for humanitarian aspects of food aid), and a reluctance to develop private-public partnerships. The emergence of new business models that tackle social problems while remaining profitable offers promise that the long term nutrition needs of people can be met. Businesses can have greater impact acting collectively than individually. Food, retail, food service, chemical and pharmaceutical companies have expertise, distribution systems and customers insights, if well harnessed, could leapfrog progress in addressing the food and nutrition crises. While business can do lots more, its combined impact will be minimal if a range of essential government actions and policies are not addressed. Governments need to create innovative and complementary opportunities that include incentives for businesses including: setting clear nutritional guidelines for fortification and for ready-to eat products; offering agreements to endorse approved products and support their distribution to clinics and schools; eliminating duties on imported vitamins and other micronutrients; and providing tax and other incentives for industry to invest with donors in essential nutrition

The role of business in addressing the long-term implications of the current food crisis

PubMed Central

Yach, Derek

2008-01-01

Before the onset of the current food crisis, the evidence of a severely neglected nutrition crisis was starting to receive attention. Increased food prices are having severe impacts on the nutritional status of populations. Our current food system has evolved over decades in a largely unplanned manner and without consideration for the complexity and implications of linkages between health, nutrition, agricultural, economic, trade and security issues. The underlying causes for the nutrition crisis include the above, as well as decades of neglect with regard to nutrition, and agricultural science (especially in emerging markets); a failure of governance with respect to the major players involved in nutrition, a weak response by government donors and Foundations to invest in basic nutrition (in contrast to growing support for humanitarian aspects of food aid), and a reluctance to develop private-public partnerships. The emergence of new business models that tackle social problems while remaining profitable offers promise that the long term nutrition needs of people can be met. Businesses can have greater impact acting collectively than individually. Food, retail, food service, chemical and pharmaceutical companies have expertise, distribution systems and customers insights, if well harnessed, could leapfrog progress in addressing the food and nutrition crises. While business can do lots more, its combined impact will be minimal if a range of essential government actions and policies are not addressed. Governments need to create innovative and complementary opportunities that include incentives for businesses including: setting clear nutritional guidelines for fortification and for ready-to eat products; offering agreements to endorse approved products and support their distribution to clinics and schools; eliminating duties on imported vitamins and other micronutrients; and providing tax and other incentives for industry to invest with donors in essential nutrition

Addressing risks to advance mental health research.

PubMed

Iltis, Ana S; Misra, Sahana; Dunn, Laura B; Brown, Gregory K; Campbell, Amy; Earll, Sarah A; Glowinski, Anne; Hadley, Whitney B; Pies, Ronald; Dubois, James M

2013-12-01

Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards may reject study designs that seem too risky. This can discourage needed research, particularly in higher-risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research. To provide mental health researchers with practical approaches to (1) identify and define various intrinsic research risks, (2) communicate these risks to others (eg, potential participants, regulatory bodies, and society), (3) manage these risks during the course of a study, and (4) justify the risks. As part of a National Institute of Mental Health-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. No institutional review board-review was required because there were no human subjects. Challenges, current data, practical strategies, and topics for future research are addressed for each of 4 key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks. Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain institutional review board-approval.

Participatory Workplace Wellness Programs: Reward, Penalty, and Regulatory Conflict

PubMed Central

Pomeranz, Jennifer L

2015-01-01

Context In keeping with the Patient Protection and Affordable Care Act, Congress revised the law related to workplace wellness programs. In June 2013, the Departments of Treasury, Labor, and Health and Human Services passed the final regulations, updating their 2006 regulatory framework. Participatory programs that reward the completion of a health risk assessment are now the most common type of wellness program in the United States. However, legal and ethical concerns emerge when employers utilize incentives that raise questions about the voluntariness of such programs. At issue is that under the Americans with Disabilities Act (ADA) of 1990, employers cannot require health-related inquiries and exams. Methods To analyze the current interpretation of the ADA, I conducted research on both LexisNexis and federal agency websites. The resulting article evaluates the differences in the language of Congress's enabling legislation and the federal departments’ regulations and how they may conflict with the ADA. It also reviews the federal government's authority to address both the legal conflict and ethical concerns related to nonvoluntary participatory programs. Findings Employers’ practices and the federal departments’ regulations conflict with the current interpretation of the ADA by permitting employers to penalize employees who do not complete a health risk assessment. The departments’ regulations may be interpreted as conflicting with Congress's legislation, which mentions penalties only for health-contingent wellness programs. Furthermore, the regulatory protections for employees applicable to health-contingent wellness programs do not apply to participatory programs. Conclusions Either Congress or the federal agencies should address the conflict among employers’ practices, the wellness regulations, and the ADA and also consider additional protections for employees. Employers can avoid ethical and legal complications by offering voluntary programs with

Regional Seminars to Address Current Nuclear Export Control Issues

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

Killinger, Mark H.

2002-07-01

The control of nuclear-related exports, a critical component of the nonproliferation regime, is facing several opportunities and challenges. As countries sign and ratify the International Atomic Energy Agency's (IAEA) safeguards Additional Protocol (AP), they will begin to report far more export information, including exports of a list of items similar to the Nuclear Supplier Group's Trigger List that existed when the AP was developed in the mid-1990s. This positive development contrasts with challenges such as globalization, transshipments, and tracking of end-uses. Pacific Northwest National Laboratory is proposing that the US Department of Energy (DOE) develop regional seminars that address thesemore » types of issues related to export/import controls. The DOE seminars would be designed to supplement regional seminars sponsored by the IAEA and member states on topics related to the Additional Protocol (referred to as "IAEA seminars"). The topic of nuclear export/import controls is not thoroughly addressed in the IAEA seminars. The proposed DOE seminars would therefore have two objectives: familiarizing countries with the export/import provisions of the Additional Protocol, and addressing challenges such as those noted above. The seminars would be directed particularly at countries that have not ratified the AP, and at regions where export-related problems are particularly prevalent. The intent is to encourage governments to implement more effective nuclear export control systems that meet the challenges of the 21st century.« less

Current regulatory issues in cell and tissue therapy.

PubMed

Burger, S R

2003-01-01

Cell-based therapies have grown dramatically in power and scope in recent years. Once limited to blood and BM transplantation, these therapies now encompass tissue repair and regeneration, metabolic support, gene replacement, and immune effector functions, with established and investigational clinical applications in disorders affecting nearly every tissue and organ system. The complexity and novel applications of human cells, tissues, and cellular and tissue-based products (HCT/Ps), however, present potential risks for adverse events. The US Food and Drug Administration, responding to these concerns, has established a tiered, risk-based regulatory structure, in which more rigorous controls and safeguards are required for products thought to pose increased risk. The proposed good tissue practices (GTP) rule and existing good manufacturing practices (GMP) requirements form the principal elements of this regulatory framework. The proposed GTPs are intended to prevent HCT/P contamination with infectious disease agents, and to ensure that these cells and tissues maintain their integrity and function. GMPs focus on production of safe, pure, and potent products, and entail a higher level of process control and product characterization. All HCT/Ps will be required to comply with GTPs. HCT/Ps considered to present greater risks of adverse events, however, will be subject to both GTPs and GMPs, and must obtain premarket approval using the Investigational New Drug (IND) mechanism established for biologics. Although these requirements will present significant challenges for clinician- investigators and laboratories producing HCT/Ps, the regulations fundamentally support good clinical care by increasing safety and control, and enable good science by improving the quality and reliability of data.

Regulatory system reform of occupational health and safety in China

PubMed Central

WU, Fenghong; CHI, Yan

2015-01-01

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

Environmental Programs: Status of Work and Current Priorities for FY13

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

Jones, Patricia

2012-08-17

Presentation outline is: Mission/overview, Regulatory framework, Current status of cleanup, Shift in priorities to address highest risk, Removal of above-ground waste, Continued focus on protecting water resources, and Priorities for fiscal year 2013. LANL's Environmental Mission is to: (1) Repack and ship legacy transuranic waste containers; (2) Investigate and remediate Cold War (legacy) hazardous and radioactive waste areas; (3) Demolish unused buildings; (4) Disposition solid waste from Laboratory operations; and (5) Lifecycle cost nearly $3 billion.

How health technology assessment agencies address the issue of unpublished data.

PubMed

Kreis, Julia; Panteli, Dimitra; Busse, Reinhard

2014-01-01

Reporting bias potentially threatens the validity of results in health technology assessment (HTA) reports. Our study aimed to explore policies and practices of HTA agencies regarding strategies to include previously unpublished data in their assessments, focusing on requests to industry for unpublished data. We included international HTA agencies with publicly available methods papers as well as HTA reports. From the methods papers and recent reports we extracted information on requests to industry and on searches in trial registries, regulatory authority Web sites and for conference abstracts. Eighteen HTA agencies and seventy-three reports were included. Agencies' methods papers showed variability regarding requests to industry (requests are routinely carried out in seven cases, not mentioned in six, at the discretion of HTA authors in three, and based on manufacturer applications in two), which were reflected in the reports investigated. As reporting of requests was limited, it often remained unclear whether unpublished data had been received. Searches in trial registries, at regulatory authorities or for conference abstracts are described as a routine or optional part of the search strategy in the methods papers of 9, 11, and 8 included agencies, respectively. A total of 52 percent, 39 percent, and 16 percent of reports described searches in trial registries, at regulatory agencies, and hand searching of conference proceedings. International HTA agencies currently differ considerably in their efforts to address the issue of unpublished data. Requests to industry may constitute one strategy to access and include unpublished data, while agencies can learn from each other concerning successful practice.

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

OVERVIEW OF VOLUNTARY STEWARDSHIP EFFORTS TO ADDRESS PHARMACEUTICAL DISPOSAL

EPA Science Inventory

This presentation will provide an overview of current federal regulatory guidance for pharmaceutical disposal, currently funded pilot programs for take-back pilot studies, and state programs. The EPA Office of Water's role is to protect our Nation's watersheds and drinking water ...

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

PubMed

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

2018-02-01

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

48 CFR 401.170 - Electronic access to regulatory information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... access to regulatory information. The USDA Departmental Administration Procurement Homepage provides... guidance in electronic form. The Internet address for the Procurement Homepage is URL http://www.usda.gov...

Department of the Treasury Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

..., money laundering, and other financial crime. The proposed changes are intended to address regulatory... for the use of prepaid access as a means for furthering money laundering, terrorist financing, and...) exempting certain categories of prepaid access products and services posing lower risks of money laundering...

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.

Regulatory Focus Affects Physician Risk Tolerance

PubMed Central

Veazie, Peter J.; McIntosh, Scott; Chapman, Benjamin P.; Dolan, James G.

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention – regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (P=0.01). The Cohen’s d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (P=0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor. PMID:25431799

Participatory workplace wellness programs: reward, penalty, and regulatory conflict.

PubMed

Pomeranz, Jennifer L

2015-06-01

POLICY POINTS: Workplace wellness programs that provide incentives for completing a health risk assessment are a form of participatory programs. There are legal and ethical concerns when employers assess penalties for not completing a health risk assessment, raising questions about the voluntariness of such a program. The Departments of Treasury, Labor, and Health and Human Services' 2013 regulations for participatory programs and employers' current practices conflict with the Equal Employment Opportunity Commission's prevailing interpretation of the Americans with Disabilities Act of 1990. In keeping with the Patient Protection and Affordable Care Act, Congress revised the law related to workplace wellness programs. In June 2013, the Departments of Treasury, Labor, and Health and Human Services passed the final regulations, updating their 2006 regulatory framework. Participatory programs that reward the completion of a health risk assessment are now the most common type of wellness program in the United States. However, legal and ethical concerns emerge when employers utilize incentives that raise questions about the voluntariness of such programs. At issue is that under the Americans with Disabilities Act (ADA) of 1990, employers cannot require health-related inquiries and exams. To analyze the current interpretation of the ADA, I conducted research on both LexisNexis and federal agency websites. The resulting article evaluates the differences in the language of Congress's enabling legislation and the federal departments' regulations and how they may conflict with the ADA. It also reviews the federal government's authority to address both the legal conflict and ethical concerns related to nonvoluntary participatory programs. Employers' practices and the federal departments' regulations conflict with the current interpretation of the ADA by permitting employers to penalize employees who do not complete a health risk assessment. The departments' regulations may be

Jabs and barbs: ways to address misleading vaccination and immunisation information using currently available strategies.

PubMed

Wardle, Jon; Stewart, Cameron; Parker, Malcolm

2013-09-01

Misleading vaccination information undermines confidence in vaccination and may lead to reductions in the effectiveness of vaccination programs. A number of regulatory techniques can be employed to challenge the spread of false information, including health care complaints, therapeutic goods laws, consumer protection laws and professional discipline. This article examines three case studies involving the publication of anti-vaccination information by non-professionally aligned organisations, by non-registered health professionals, and by registered health professionals under the National Law. The article examines the effectiveness of different regulatory responses and makes suggestions for future strategies to deal with the publication of demonstrably false information regarding vaccination.

Mesenchymal Stem Cells as Therapeutics Agents: Quality and Environmental Regulatory Aspects

PubMed Central

Sabata, Roger; Verges, Josep; Zugaza, José L.; Ruiz, Adolfina; Clares, Beatriz

2016-01-01

Mesenchymal stem cells (MSCs) are one of the main stem cells that have been used for advanced therapies and regenerative medicine. To carry out the translational clinical application of MSCs, their manufacturing and administration in human must be controlled; therefore they should be considered as medicine: stem cell-based medicinal products (SCMPs). The development of MSCs as SCMPs represents complicated therapeutics due to their extreme complex nature and rigorous regulatory oversights. The manufacturing process of MSCs needs to be addressed in clean environments in compliance with requirements of Good Manufacturing Practice (GMP). Facilities should maintain these GMP conditions according to international and national medicinal regulatory frameworks that introduce a number of specifications in order to produce MSCs as safe SCMPs. One of these important and complex requirements is the environmental monitoring. Although a number of environmental requirements are clearly defined, some others are provided as recommendations. In this review we aim to outline the current issues with regard to international guidelines which impact environmental monitoring in cleanrooms and clean areas for the manufacturing of MSCs. PMID:27999600

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.

Regulatory Promotion of Emergent CCS Technology

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

Davies, Lincoln; Uchitel, Kirsten; Johnson, David

2014-01-01

Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensivemore » regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.« 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.

Proposed Activities to Address Regulatory Gaps and Challenges for Licensing Advanced Reactors Using Seismic Isolation

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

Coleman, Justin Leigh; Kammerer, Annie M.; Whittaker, Andrew S.

Over the last decade, particularly since implementation of the certified design regulatory approaches outlined in 10 CFR 52, “Licenses, Certifications, and Approvals for Nuclear Power Plants,” interest has been increasing in the use of seismic isolation (SI) technology to support seismic safety in nuclear facilities. In 2009, the United States (U.S.) Nuclear Regulatory Commission (NRC) initiated research activities to develop new guidance targeted at isolated facilities because SI is being considered for nuclear power plants in the U.S. One product of that research, which was developed around a risk-informed regulatory approach, is a draft NRC NUREG series (NUREG/CR) report thatmore » investigates and discusses considerations for use of SI in otherwise traditionally founded large light water reactors (LWRs). A coordinated effort led to new provisions for SI of LWRs in the American Society of Civil Engineers standard ASCE/SEI 4-16, “Seismic Analysis of Safety Related Nuclear Structures.” The risk-informed design philosophy that underpinned development of the technical basis for these documents led to a set of proposed performance objectives and acceptance criteria intended to serve as the foundation for future NRC guidance on the use of SI and related technology. Although the guidance provided in the draft SI NUREG/CR report and ASCE/SEI 4 16 provides a sound basis for further development of nuclear power plant designs incorporating SI, these initial documents were focused on surface-founded or near-surface-founded LWRs and were, necessarily, limited in scope. For example, there is limited information in both the draft NUREG/CR report and ASCE/SEI 4-16 related to nonlinear analysis of soil-structure systems for deeply-embedded reactors, the isolation of components, and the use of vertical isolation systems. Also not included in the draft SI NUREG/CR report are special considerations for licensing of isolated facilities using the certified design approach

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.

Science in the regulatory setting: a challenging but incompatible mix?

PubMed

Yetley, Elizabeth A

2007-01-01

Regulatory decisions informed by sound science have an important role in many regulatory applications involving drugs and foods, including applications related to dietary supplements. However, science is only one of many factors that must be taken into account in the regulatory decision-making process. In many cases, the scientific input to a regulatory decision must compete with other factors (e.g. economics, legal requirements, stakeholder interests) for impact on the resultant policy decision. Therefore, timely and effective articulation of the available science to support a regulatory decision can significantly affect the relative weight given to science. However, the incorporation of science into the regulatory process for dietary supplements is often fraught with challenges. The available scientific evidence has rarely been designed for the purpose of addressing regulatory questions and is often preliminary and of widely varying scientific quality. To add to the confusion, the same scientific evidence may result in what appears to be different regulatory decisions because the context in which the science is used differs. The underlying assumption is that scientists who have a basic understanding of the interface between science and policy decisions can more effectively provide scientific input into these decisions.

Using Patient Avatars to Promote Health Data Sharing Applications: Perspectives and Regulatory Challenges.

PubMed

Dahi, Alan; Forgó, Nikolaus; Jensen, Sarah; Stauch, Marc

2016-04-01

The potential of ICT to address problems in modern healthcare is considerable, and an ICT-driven revolution in healthcare appears imminent. Such developments maybe viewed largely in positive terms. Thus they should result in enhanced treatment and care options, empowering patients--including by permitting greater self-management of illness outside hospital, while offering economic benefits and costs savings over traditional healthcare provision. However, the new possibilities also present manifold risks, such as of data breaches, encroachments on subject autonomy, as well as of other harms. This article considers some of the key regulatory challenges against the background of the progress of the current EU Commission-sponsored 'MyHealthAvatar' project.

The Role of Nutrition-Related Initiatives in Addressing Community Health Needs Assessments

ERIC Educational Resources Information Center

George, Daniel R.; Rovniak, Liza S.; Dillon, Judy; Snyder, Gail

2017-01-01

Academic Health Centers and nonprofit hospitals are exploring strategies to meet Affordable Care Act mandates requiring tax-exempt institutions to address community health needs, which commonly include major chronic illnesses. We explore the implications of this regulatory landscape, describing methods that nonprofit health care institutions are…

Telecommunications Policy Research Conference 1987. Program [and] Keynote Address by Morris Tanenbaum.

ERIC Educational Resources Information Center

Telecommunications Policy Research Conference, Inc., Washington, DC.

Panelists, discussants, and speakers at the 20 sessions of this three-day conference on telecommunications policy research are listed under the appropriate sessions in this conference program, as well luncheon and dinner speakers. Topics addressed by the various sessions include: federal regulatory policies and technical change in…

The Regulatory Framework for Privacy and Security

NASA Astrophysics Data System (ADS)

Hiller, Janine S.

The internet enables the easy collection of massive amounts of personally identifiable information. Unregulated data collection causes distrust and conflicts with widely accepted principles of privacy. The regulatory framework in the United States for ensuring privacy and security in the online environment consists of federal, state, and self-regulatory elements. New laws have been passed to address technological and internet practices that conflict with privacy protecting policies. The United States and the European Union approaches to privacy differ significantly, and the global internet environment will likely cause regulators to face the challenge of balancing privacy interests with data collection for many years to come.

For telehealth to succeed, privacy and security risks must be identified and addressed.

PubMed

Hall, Joseph L; McGraw, Deven

2014-02-01

The success of telehealth could be undermined if serious privacy and security risks are not addressed. For example, sensors that are located in a patient's home or that interface with the patient's body to detect safety issues or medical emergencies may inadvertently transmit sensitive information about household activities. Similarly, routine data transmissions from an app or medical device, such as an insulin pump, may be shared with third-party advertisers. Without adequate security and privacy protections for underlying telehealth data and systems, providers and patients will lack trust in the use of telehealth solutions. Although some federal and state guidelines for telehealth security and privacy have been established, many gaps remain. No federal agency currently has authority to enact privacy and security requirements to cover the telehealth ecosystem. This article examines privacy risks and security threats to telehealth applications and summarizes the extent to which technical controls and federal law adequately address these risks. We argue for a comprehensive federal regulatory framework for telehealth, developed and enforced by a single federal entity, the Federal Trade Commission, to bolster trust and fully realize the benefits of telehealth.

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.

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.

Facing regulatory challenges of on-line hemodiafiltration.

PubMed

Kümmerle, Wolfgang

2011-01-01

On-line hemodiafiltration (on-line HDF) is the result of a vision that triggered multifarious changes in very different areas. Driven by the idea to offer better medical treatment for renal patients, technological innovations were developed and established that also constituted new challenges in the field of regulatory affairs. The existing regulations predominantly addressed the quality and safety of those products needed to perform dialysis treatment which were supplied by industrial manufacturers. However, the complexity of treatment system required for the provision of on-line fluids demanded a holistic approach encompassing all components involved. Hence, focus was placed not only on single products, but much more on their interfacing, and the clinical infrastructure, in particular, had to undergo substantial changes. The overall understanding of the interaction between such factors, quite different in their nature, was crucial to overcome the arising regulatory obstacles. This essay describes the evolution of the on-line HDF procedure from the regulatory point of view. A simplified diagram demonstrates the path taken from the former regulatory understanding to the realization of necessary changes. That achievement was only possible through 'management of preview' and consequent promotion of technical and medical innovations as well as regulatory re-evaluations. Copyright © 2011 S. Karger AG, Basel.

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.

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

ERIC Educational Resources Information Center

American Chemical Society, Washington, DC.

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

Toward a Regulatory Framework for the Waterpipe.

PubMed

Salloum, Ramzi G; Asfar, Taghrid; Maziak, Wasim

2016-10-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion.

Toward a Regulatory Framework for the Waterpipe

PubMed Central

Salloum, Ramzi G.; Asfar, Taghrid

2016-01-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion. PMID:27552262

MicroRNA-mediated regulatory circuits: outlook and perspectives

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

47 CFR 1.1155 - Schedule of regulatory fees and filing locations for cable television services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Schedule of regulatory fees and filing locations for cable television services. 1.1155 Section 1.1155 Telecommunication FEDERAL COMMUNICATIONS... Schedule of regulatory fees and filing locations for cable television services. Fee amount Address 1. Cable...

A proposed definition of microbiota transplantation for regulatory purposes

PubMed Central

Hoffmann, Diane E.; Palumbo, Francis B.; Rowthorn, Virginia; von Rosenvinge, Erik

2017-01-01

ABSTRACT The advent of fecal microbiota transplantation (FMT) and the prospect of other types of microbiota transplants (MT), e.g. vaginal, skin, oral and nasal, are challenging regulatory agencies. Although FDA is regulating FMT (as a biologic), there is currently no widely accepted or agreed upon scientific or legal definition of FMT or MT. The authors report on discussions regarding a definition of MT that took place among a working group of stakeholders convened under a National Institutes for Allergies and Infectious Diseases grant to address the regulation of MT. In arriving at a definition, the group considered the 1) nature of the material being transplanted; 2) degree of manipulation of the transferred materials prior to implantation; 3) ability to characterize the transplanted product using external techniques; and 4) origin of the stool product (single vs multiple donors). PMID:28318396

Regulatory affairs and biotechnology in Europe. I. Introduction into good regulatory practice.

PubMed

Tryzelaar, B

1988-01-01

The high cost and risks associated with the research and development of new drugs demand an alert as well as realistic legislative policy at both national and international levels. Registration of a new drug required before a marketing license is granted, is important for all branches of the pharmaceutical industry but is crucial for success in the innovative biotechnological sector. Innovation as such is no guarantee to be profitable. Increasing government demands have introduced uncertainty on whether new products will secure registration and have led to a disproportionate increase in the economical risks for innovative industry. Preparation and submission of an application for registration should be undertaken seriously and professionally since it has significantly more consequences than simply obtaining a marketing licence. It will influence marketing strategies and results. It is proposed--since dealing with regulatory affairs can be considered as an essential specialism--to apply a Quality Assurance approach. Activities in this context should comply with the same performance standards as developed for GMP, GLP and GCP leading to Good Regulatory Practice (GRP). By acknowledging regulatory affairs as a quality assurance means one can define a set of standard procedures within an organization to ensure that decisions are made on current and future regulations. In such a setup regulatory affairs becomes a marketing tool. This paper illustrates the complex problems found in registration activities. It underlines the necessity of introducing a GRP-approach of performance resulting in substantive evidence of regulatory efficacy.

Uterus transplantation: ethical and regulatory challenges.

PubMed

Arora, Kavita Shah; Blake, Valarie

2014-06-01

Moving forward rapidly in the clinical research phase, uterus transplantation may be a future treatment option for women with uterine factor infertility, which accounts for three per cent of all infertility in women. This new method of treatment would allow women, who currently rely on gestational surrogacy or adoption, to gestate and birth their own genetic offspring. Since uterus transplantation carries significant risk when compared with surrogacy and adoption as well as when compared with other organ transplants, it requires greater justification because its goals are quality of life, not life-saving, in their scope. It is important to address questions regarding the physical, psychosocial and ethical risks and benefits of uterus transplantation for all three parties involved--the patient, the donor and the potential child--as well as discuss the regulatory implications as research on uterus transplantations moves forward. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

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...

Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

PubMed

Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

2015-08-26

The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Radio-ecological characterization and radiological assessment in support of regulatory supervision of legacy sites in northwest Russia.

PubMed

Sneve, M K; Kiselev, M; Shandala, N K

2014-05-01

The Norwegian Radiation Protection Authority has been implementing a regulatory cooperation program in the Russian Federation for over 10 years, as part of the Norwegian government's Plan of Action for enhancing nuclear and radiation safety in northwest Russia. The overall long-term objective has been the enhancement of safety culture and includes a special focus on regulatory supervision of nuclear legacy sites. The initial project outputs included appropriate regulatory threat assessments, to determine the hazardous situations and activities which are most in need of enhanced regulatory supervision. In turn, this has led to the development of new and updated norms and standards, and related regulatory procedures, necessary to address the often abnormal conditions at legacy sites. This paper presents the experience gained within the above program with regard to radio-ecological characterization of Sites of Temporary Storage for spent nuclear fuel and radioactive waste at Andreeva Bay and Gremikha in the Kola Peninsula in northwest Russia. Such characterization is necessary to support assessments of the current radiological situation and to support prospective assessments of its evolution. Both types of assessments contribute to regulatory supervision of the sites. Accordingly, they include assessments to support development of regulatory standards and guidance concerning: control of radiation exposures to workers during remediation operations; emergency preparedness and response; planned radionuclide releases to the environment; development of site restoration plans, and waste treatment and disposal. Examples of characterization work are presented which relate to terrestrial and marine environments at Andreeva Bay. The use of this data in assessments is illustrated by means of the visualization and assessment tool (DATAMAP) developed as part of the regulatory cooperation program, specifically to help control radiation exposure in operations and to support

2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 2 - hybrid LBA/LCMS and input from regulatory agencies).

PubMed

Ackermann, Brad; Neubert, Hendrik; Hughes, Nicola; Garofolo, Fabio; Abberley, Lee; Alley, Stephen C; Brown-Augsburger, Patricia; Bustard, Mark; Chen, Lin-Zhi; Heinrich, Julia; Katori, Noriko; Kaur, Surinder; Kirkovsky, Leo; Laterza, Omar F; Le Blaye, Olivier; Lévesque, Ann; Santos, Gustavo Mendes Lima; Olah, Timothy; Savoie, Natasha; Skelly, Michael; Spitz, Susan; Szapacs, Matthew; Tampal, Nilufer; Wang, Jian; Welink, Jan; Wieling, Jaap; Haidar, Sam; Vinter, Stephen; Whale, Emma; Witte, Bärbel

2015-12-01

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations that emerged from the extensive discussions held during the workshop, and is aimed at providing the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to advance scientific excellence, improve quality and deliver better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 2 covers the recommendations for hybrid LBA/LCMS and regulatory agencies' inputs. Part 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in volume 7 of Bioanalysis, issues 22 and 24, respectively.

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 2 - Hybrid LBA/LCMS and input from regulatory agencies).

PubMed

Song, An; Lee, Anita; Garofolo, Fabio; Kaur, Surinder; Duggan, Jeff; Evans, Christopher; Palandra, Joe; Donato, Lorella Di; Xu, Keyang; Bauer, Ronald; Bustard, Mark; Chen, Linzhi; Cocea, Laurent; Croft, Stephanie; Galliccia, Fabrizio; Haidar, Sam; Hughes, Nicola; Ishii-Watabe, Akiko; Islam, Rafiqul; Jones, Barry; Kadavil, John; Krantz, Carsten; Lima Santos, Gustavo Mendes; Olah, Timothy; Pedras-Vasconcelos, João; Staelens, Ludovicus; Saito, Yoshiro; Savoie, Natasha; Scheibner, Kara; Spitz, Susan; Tampal, Nilufer; Thomas, Eric; Vinter, Stephen; Wakelin-Smith, Jason; Welink, Jan; Zeng, Jianing; Zhou, Shaolian

2016-12-01

The 2016 10th Workshop on Recent Issues in Bioanalysis (10 th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 2) discusses the recommendations for Hybrid LBA/LCMS and regulatory inputs from major global health authorities. Parts 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) have been published in the Bioanalysis journal, issues 22 and 23, respectively.

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions.

PubMed

Tralau, Tewes; Oelgeschläger, Michael; Gürtler, Rainer; Heinemeyer, Gerhard; Herzler, Matthias; Höfer, Thomas; Itter, Heike; Kuhl, Thomas; Lange, Nikola; Lorenz, Nicole; Müller-Graf, Christine; Pabel, Ulrike; Pirow, Ralph; Ritz, Vera; Schafft, Helmut; Schneider, Heiko; Schulz, Thomas; Schumacher, David; Zellmer, Sebastian; Fleur-Böl, Gaby; Greiner, Matthias; Lahrssen-Wiederholt, Monika; Lampen, Alfonso; Luch, Andreas; Schönfelder, Gilbert; Solecki, Roland; Wittkowski, Reiner; Hensel, Andreas

2015-06-01

The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

"Letting myself go forward past wrongs": How regulatory modes affect self-forgiveness

PubMed Central

Giannini, Anna Maria; Higgins, E. Tory; Kruglanski, Arie W.

2018-01-01

The present research addresses the question of whether regulatory-mode orientations affect self-forgiveness. We expected that people with a strong locomotion orientation would be more inclined to self-forgiveness because of their tendencies toward movement and change, which focus them on the future, whereas people with a strong assessment orientation would refrain from self-forgiveness due to their evaluative tendencies which focus them on the past. These hypotheses were supported by the results in four studies that tested the relation between regulatory modes and self-forgiveness by measuring (Studies 1, 3 and 4) and manipulating (Study 2) regulatory-mode-orientations. Finally, in Study 4 we examined more closely our hypothesis that the relation between self-forgiveness and regulatory modes is mediated by past and future temporal foci. The implications of the results for regulatory mode theory are also discussed. PMID:29529065

"Letting myself go forward past wrongs": How regulatory modes affect self-forgiveness.

PubMed

Pierro, Antonio; Pica, Gennaro; Giannini, Anna Maria; Higgins, E Tory; Kruglanski, Arie W

2018-01-01

The present research addresses the question of whether regulatory-mode orientations affect self-forgiveness. We expected that people with a strong locomotion orientation would be more inclined to self-forgiveness because of their tendencies toward movement and change, which focus them on the future, whereas people with a strong assessment orientation would refrain from self-forgiveness due to their evaluative tendencies which focus them on the past. These hypotheses were supported by the results in four studies that tested the relation between regulatory modes and self-forgiveness by measuring (Studies 1, 3 and 4) and manipulating (Study 2) regulatory-mode-orientations. Finally, in Study 4 we examined more closely our hypothesis that the relation between self-forgiveness and regulatory modes is mediated by past and future temporal foci. The implications of the results for regulatory mode theory are also discussed.

Glycoconjugate Vaccines: The Regulatory Framework.

PubMed

Jones, Christopher

2015-01-01

Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

Regulatory forum opinion piece*: supporting the need for international harmonization of safety assessments for food flavoring substances.

PubMed

Konishi, Yoichi; Hayashi, Shim-Mo; Fukushima, Shoji

2014-08-01

The advancement of technology and the growth of international commerce underscore the need for global harmonization of regulatory safety requirements and their assessment pertaining to consumer products such as drugs, medical devices, and food. This need is particularly relevant when safety requirements involve time-intensive and costly animal safety studies. Here we present the current regulatory requirements in Europe, the United States, and Japan for flavoring substances (FSs) used in foods and point out significant differences relevant to the international standardization for safety assessments that in our opinion need to be addressed and overcome. The safety assessments that are carried out for FSs in various countries are influenced by divergent definitions of FS, by the information required and available for regulatory submission, and by different regulatory procedures, including the use of decision tree approaches. The European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) are making efforts to improve and harmonize the safety assessment of FSs. The application of in silico methods such as quantitative structure-activity relationships and read-across strategies relying on expert input are useful as a first-step screening of the assessment. Application of the Threshold of Toxicological Concern (TTC) approach permits conclusions that are compatible with the risk assessment approaches currently used by international advisory committees. The Japanese Regulatory Authority, on the other hand, does not yet consider in silico methods but still requires in vivo and in vitro genotoxicity test data as well as repeat-dose 90-day toxicity data in at least one species, to be submitted as the first step in the safety assessment of FSs. With this article, we echo requests that have

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.

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

Understanding and Addressing Racial Disparities in Health Care

PubMed Central

Williams, David R.; Rucker, Toni D.

2000-01-01

Racial disparities in medical care should be understood within the context of racial inequities in societal institutions. Systematic discrimination is not the aberrant behavior of a few but is often supported by institutional policies and unconscious bias based on negative stereotypes. Effectively addressing disparities in the quality of care requires improved data systems, increased regulatory vigilance, and new initiatives to appropriately train medical professionals and recruit more providers from disadvantaged minority backgrounds. Identifying and implementing effective strategies to eliminate racial inequities in health status and medical care should be made a national priority. PMID:11481746

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.

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

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

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

PubMed

Borodovsky, Jacob T; Budney, Alan J

2018-05-29

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

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.

Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

PubMed

Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

2017-11-01

Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

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

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe

PubMed Central

Spicer, Andrew

2018-01-01

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe. PMID:29509719

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe.

PubMed

Spicer, Andrew; Molnar, Attila

2018-03-06

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe.

A regulatory perspective on the radiological impact of NORM industries: the case of the Spanish phosphate industry.

PubMed

García-Talavera, M; Matarranz, J L M; Salas, R; Ramos, L

2011-01-01

Radioactive and chemical risks coexist in NORM industries although they are usually addressed separately by regulations. The European Union (EU) has developed extensive legislation concerning both matters, which has been diversely reflected in national policies. We consider the case of the Spanish phosphate industry and analyse to which extent regulatory mandates have reduced the historical and ongoing radiological impact on the environment of phosphate facilities. Although no specific radiological constraints on effluent monitoring and release or on waste disposal have yet been imposed on NORM industries in Spain, other environmental regulations have achieved a substantial reduction on the phosphate industry impact. Nevertheless, a more efficient control could be established by eliminating the current conceptual and practical separation of chemical and radioactive risks in NORM industries. We highlight research needs to accomplish so and propose shorter-term measures that require active cooperation among the regulatory bodies involved. Copyright © 2010. Published by Elsevier Ltd.

Addressing Theory and Performance Enhancements for the Independent Sustain and Address AC Plasma Display

NASA Astrophysics Data System (ADS)

Warren, Kevin Wilson

The Independent Sustain and Address (ISA) AC plasma panel is a flat, flicker-free, gas discharge type of display device. This display technology promises to reduce both the cost of manufacturing and operation of AC plasma displays. The ISA technology uses a vastly different mechanism to change the state of the display pixels than the standard AC plasma technology. This addressing mechanism is an exploitation of some of the natural characteristics associated with the plasma that can form during strong gas discharges. This thesis presents detailed data from experiments that were designed to evaluate and test the effectiveness of this mechanism. Through these experiments, the theory that the addressing methodology is based upon is developed and evaluated. These experiments show that the address margin windows for this technology are very large, minimally two to three times larger than the address margins for the standard XY AC plasma addressing techniques. New capabilities are also described, such as global brightness control for the ISA technology and a technique for increasing the addressing rate. These advances were designed into working prototypes and transferred to industry where there are currently commercial products available based upon these advances. A technique for implementing gray scale using some of these advances is also proposed.

2017 White Paper: rise of hybrid LBA/LCMS immunogenicity assays (Part 2: hybrid LBA/LCMS biotherapeutics, biomarkers & immunogenicity assays and regulatory agencies' inputs).

PubMed

Neubert, Hendrik; Song, An; Lee, Anita; Wei, Cong; Duggan, Jeff; Xu, Keyang; Woolf, Eric; Evans, Chris; Palandra, Joe; Laterza, Omar; Amur, Shashi; Berger, Isabella; Bustard, Mark; Cancilla, Mark; Chen, Shang-Chiung; Cho, Seongeun Julia; Ciccimaro, Eugene; Cludts, Isabelle; Cocea, Laurent; D'Arienzo, Celia; Danan-Leon, Lieza; Donato, Lorella Di; Garofolo, Fabio; Haidar, Sam; Ishii-Watabe, Akiko; Jiang, Hao; Kadavil, John; Kassim, Sean; Kurki, Pekka; Blaye, Olivier Le; Liu, Kai; Mathews, Rod; Lima Santos, Gustavo Mendes; Niwa, Makoto; Pedras-Vasconcelos, João; Qian, Mark; Rago, Brian; Saad, Ola; Saito, Yoshiro; Savoie, Natasha; Su, Dian; Szapacs, Matthew; Tampal, Nilufer; Vinter, Stephen; Wang, Jian; Welink, Jan; Whale, Emma; Wilson, Amanda; Xue, Y-J

2017-12-01

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid ligand binding assay (LBA)/LCMS and LBA approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for biotherapeutics, biomarkers and immunogenicity assays using hybrid LBA/LCMS and regulatory agencies' inputs. Part 1 (LCMS for small molecules, peptides and small molecule biomarkers) and Part 3 (LBA: immunogenicity, biomarkers and pharmacokinetic assays) are published in Volume 9 of Bioanalysis, issues 22 and 24 (2017), respectively.

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.

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

PubMed

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

2018-05-16

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

Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs) in Taiwan

PubMed Central

Tsai, Wen-Tien

2010-01-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years. PMID:21139852

Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan.

PubMed

Tsai, Wen-Tien

2010-10-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years.

Regulatory Aspects of Smart Water Networks in the U.S.

EPA Science Inventory

The presentation addresses regulatory aspects of smart water networks in the U.S. It will be presented at the Smart Water Networks Forum (SWAN) annual conference in London, England from April 29-30, 2015. The conference will bring together key voices in the smart water space f...

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

EPA Science Inventory

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 organizatio...

Clostridium difficile infection: current, forgotten and emerging treatment options.

PubMed

Drekonja, Dimitri M

2014-09-01

Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.

Functional analysis of regulatory single-nucleotide polymorphisms.

PubMed

Pampín, Sandra; Rodríguez-Rey, José C

2007-04-01

The identification of regulatory polymorphisms has become a key problem in human genetics. In the past few years there has been a conceptual change in the way in which regulatory single-nucleotide polymorphisms are studied. We revise the new approaches and discuss how gene expression studies can contribute to a better knowledge of the genetics of common diseases. New techniques for the association of single-nucleotide polymorphisms with changes in gene expression have been recently developed. This, together with a more comprehensive use of the old in-vitro methods, has produced a great amount of genetic information. When added to current databases, it will help to design better tools for the detection of regulatory single-nucleotide polymorphisms. The identification of functional regulatory single-nucleotide polymorphisms cannot be done by the simple inspection of DNA sequence. In-vivo techniques, based on primer-extension, and the more recently developed 'haploChIP' allow the association of gene variants to changes in gene expression. Gene expression analysis by conventional in-vitro techniques is the only way to identify the functional consequences of regulatory single-nucleotide polymorphisms. The amount of information produced in the last few years will help to refine the tools for the future analysis of regulatory gene variants.

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

PubMed

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

2014-01-01

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

Addressing current and future challenges for the NHS: the role of good leadership.

PubMed

Elton, Lotte

2016-10-03

Purpose This paper aims to describe and analyse some of the ways in which good leadership can enable those working within the National Health Service (NHS) to weather the changes and difficulties likely to arise in the coming years, and takes the format of an essay written by the prize-winner of the Faculty of Medical Leadership and Management's Student Prize. The Faculty of Medical Leadership and Management ran its inaugural Student Prize in 2015-2016, which aimed at medical students with an interest in medical leadership. In running the Prize, the Faculty hoped to foster an enthusiasm for and understanding of the importance of leadership in medicine. Design/methodology/approach The Faculty asked entrants to discuss the role of good leadership in addressing the current and future challenges faced by the NHS, making reference to the Leadership and Management Standards for Medical Professionals published by the Faculty in 2015. These standards were intended to help guide current and future leaders and were grouped into three categories, namely, self, team and corporate responsibility. Findings This paper highlights the political nature of health care in the UK and the increasing impetus on medical professionals to navigate debates on austerity measures and health-care costs, particularly given the projected deficit in NHS funding. It stresses the importance of building organisational cultures prizing transparency to prevent future breaches in standards of care and the value of patient-centred approaches in improving satisfaction for both patients and staff. Identification of opportunities for collaboration and partnership is emphasised as crucial to assuage the burden that lack of appropriate social care places on clinical services. Originality/value This paper offers a novel perspective - that of a medical student - on the complex issues faced by the NHS over the coming years and utilises a well-regarded set of standards in conceptualising the role that health

Regulatory landscape for cell therapy--EU view.

PubMed

McBlane, James W

2015-09-01

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

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.

Enhancing Tissue Engineering and Regenerative Medicine Product Commercialization: The Role of Science in Regulatory Decision-Making for the TE/RM Product Development.

PubMed

Bertram, Timothy A; Johnson, Peter C; Tawil, Bill J; Van Dyke, Mark; Hellman, Kiki B

2015-10-01

TERMIS-AM Industry Committee (TERMIS-AM/IC), in collaboration with the TERMIS-Europe (EU)/IC, conducted a symposium involving the European Medicines Agency and the U.S. Food and Drug Administration (FDA) toward building an understanding of the rational basis for regulatory decision-making and providing a framework for decisions made during the evaluation of safety and efficacy of TE/RM technologies. This symposium was held in August 2012 during the TERMIS-WC in Vienna, Austria. Emerging from this international initiative by the European Union and the United States, representatives from the respective agencies demonstrated that there are ongoing interagency efforts for developing common national practices toward harmonization of regulatory requirements for the TE/RM products. To extend a broad-based understanding of the role of science in regulatory decision-making, TERMIS-AM/IC, in cooperation with the FDA, organized a symposium at the 2014 TERMIS-AM Annual Meeting, which was held in Washington, DC. This event provided insights from leaders in the FDA and TERMIS on the current status of regulatory approaches for the approved TE/RM products, the use of science in making regulatory decisions, and TE/RM technologies that are in the development pipeline to address unmet medical needs. A far-ranging discussion with FDA representatives, industrialists, physicians, regenerative medicine biologists, and tissue engineers considered the gaps in today's scientific and regulatory understanding of TE/RM technologies. The identified gaps represent significant opportunities to advance TE/RM technologies toward commercialization.

Regulatory aspects of oncology drug safety evaluation: past practice, current issues, and the challenge of new drugs.

PubMed

Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M Stacey; McGuinn, W David; Verbois, S Leigh

2010-03-01

The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

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

A Multi-Systemic School-Based Approach for Addressing Childhood Aggression

ERIC Educational Resources Information Center

Runions, Kevin

2008-01-01

School-based approaches to addressing aggression in the early grades have focused on explicit curriculum addressing social and emotional processes. The current study reviews research on the distinct modes of aggression, the status of current research on social and emotional processing relevant to problems of aggression amongst young children, as…

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.

Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers.

PubMed

Eichler, Hans-Georg; Bloechl-Daum, Brigitte; Abadie, Eric; Barnett, David; König, Franz; Pearson, Steven

2010-04-01

Drug regulatory agencies have traditionally assessed the quality, safety and efficacy of drugs, and the current paradigm dictates that a new drug should be licensed when the benefits outweigh the risks. By contrast, third-party payers base their reimbursement decisions predominantly on the health benefits of the drug relative to existing treatment options (termed relative efficacy; RE). Over the past decade, the role of payers has become more prominent, and time-to-market no longer means time-to-licensing but time-to-reimbursement. Companies now have to satisfy the sometimes divergent needs of both regulators and payers, and to address RE during the pre-marketing stages. This article describes the current political background to the RE debate and presents the scientific and methodological challenges as they relate to RE assessment. In addition, we explain the impact of RE on drug development, and speculate on future developments and actions that are likely to be required from key players.

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

Paving the road to personalized medicine: recommendations on regulatory, intellectual property and reimbursement challenges

PubMed Central

Knowles, Lori; Luth, Westerly; Bubela, Tania

2017-01-01

Abstract Personalized medicine (PM) aims to harness a wave of ‘omics’ discoveries to facilitate research and discovery of targeted diagnostics and therapies and increase the efficiency of healthcare systems by predicting and treating individual predispositions to diseases or conditions. Despite significant investment, limited progress has been made bringing PM to market. We describe the major perceived regulatory, intellectual property, and reimbursement challenges to the development, translation, adoption, and implementation of PM products into clinical care. We conducted a scoping review to identify (i) primary challenges for the development and implementation of PM identified in the academic literature; (ii) solutions proposed in the academic literature to address these challenges; and (iii) gaps that exist in that literature. We identified regulatory barriers to PM development and recommendations in 344 academic papers. Regulatory uncertainty was a cross-cutting theme that appeared in conjunction with other themes including: reimbursement; clinical trial regulation; regulation of co-development; unclear evidentiary requirements; insufficient incentives for research and development; incompatible information systems; and different regulation of different diagnostics. To fully realize the benefits of PM for healthcare systems and patients, regulatory, intellectual property, and reimbursement challenges need to be addressed in lock step with scientific advances. PMID:29868182

78 FR 35072 - Proposed Revision to Strategies and Guidance to Address Loss of Large Areas of the Plant Due to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... Address Loss of Large Areas of the Plant Due to Explosions and Fires AGENCY: Nuclear Regulatory Commission... Standard Review Plan (SRP), Section 19.4 ``Strategies and Guidance to Address Loss of Large Areas of the... review of the subject of loss-of-large areas of the plant due to explosions and fires. DATES: Submit...

Framing of information on the use of public finances, regulatory fit of recipients and tax compliance

PubMed Central

Holler, Marianne; Hoelzl, Erik; Kirchler, Erich; Leder, Susanne; Mannetti, Lucia

2010-01-01

Information campaigns to increase tax compliance could be framed in different ways. They can either highlight the potential gains when tax compliance is high, or the potential losses when compliance is low. According to regulatory focus theory, such framing should be most effective when it is congruent with the promotion or prevention focus of its recipients. Two studies confirmed the hypothesized interaction effects between recipients' regulatory focus and framing of information campaigns, with tax compliance being highest under conditions of regulatory fit. To address taxpayers effectively, information campaigns by tax authorities should consider the positive and negative framing of information, and the moderating effect of recipients' regulatory focus. PMID:20495689

Framing of information on the use of public finances, regulatory fit of recipients and tax compliance.

PubMed

Holler, Marianne; Hoelzl, Erik; Kirchler, Erich; Leder, Susanne; Mannetti, Lucia

2008-08-01

Information campaigns to increase tax compliance could be framed in different ways. They can either highlight the potential gains when tax compliance is high, or the potential losses when compliance is low. According to regulatory focus theory, such framing should be most effective when it is congruent with the promotion or prevention focus of its recipients. Two studies confirmed the hypothesized interaction effects between recipients' regulatory focus and framing of information campaigns, with tax compliance being highest under conditions of regulatory fit. To address taxpayers effectively, information campaigns by tax authorities should consider the positive and negative framing of information, and the moderating effect of recipients' regulatory focus.

Implementation of the 3Rs (refinement, reduction, and replacement): validation and regulatory acceptance considerations for alternative toxicological test methods.

PubMed

Schechtman, Leonard M

2002-01-01

Toxicological testing in the current regulatory environment is steeped in a history of using animals to answer questions about the safety of products to which humans are exposed. That history forms the basis for the testing strategies that have evolved to satisfy the needs of the regulatory bodies that render decisions that affect, for the most part, virtually all phases of premarket product development and evaluation and, to a lesser extent, postmarketing surveillance. Only relatively recently have the levels of awareness of, and responsiveness to, animal welfare issues reached current proportions. That paradigm shift, although sluggish, has nevertheless been progressive. New and alternative toxicological methods for hazard evaluation and risk assessment have now been adopted and are being viewed as a means to address those issues in a manner that considers humane treatment of animals yet maintains scientific credibility and preserves the goal of ensuring human safety. To facilitate this transition, regulatory agencies and regulated industry must work together toward improved approaches. They will need assurance that the methods will be reliable and the results comparable with, or better than, those derived from the current classical methods. That confidence will be a function of the scientific validation and resultant acceptance of any given method. In the United States, to fulfill this need, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its operational center, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), have been constituted as prescribed in federal law. Under this mandate, ICCVAM has developed a process and established criteria for the scientific validation and regulatory acceptance of new and alternative methods. The role of ICCVAM in the validation and acceptance process and the criteria instituted toward that end are described. Also

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

Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora

PubMed Central

Steige, Kim A.; Laenen, Benjamin; Reimegård, Johan; Slotte, Tanja

2017-01-01

Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora. We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species. PMID:28096395

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

Economic analysis requirements in support of orbital debris regulatory policy

NASA Astrophysics Data System (ADS)

Greenberg, Joel S.

1996-10-01

As the number of Earth orbiting objects increases so does the potential for generating orbital debris with the consequent increase in the likelihood of impacting and damaging operating satellites. Various debris remediation approaches are being considered that encompass both in-orbit and return-to-Earth schema and have varying degrees of operations, cost, international competitiveness, and safety implications. Because of the diversity of issues, concerns and long-term impacts, there is a clear need for the setting of government policies that will lead to an orderly abatement of the potential orbital debris hazards. These policies may require the establishment of a supportive regulatory regime. The Department of Transportation is likely to have regulatory responsibilities relating to orbital debris stemming from its charge to protect the public health and safety, safety of property, and national security interests and foreign policy interests of the United States. This paper describes DOT's potential regulatory role relating to orbital debris remediation, the myriad of issues concerning the need for establishing government policies relating to orbital debris remediation and their regulatory implications, the proposed technological solutions and their economic and safety implications. Particular emphasis is placed upon addressing cost-effectiveness and economic analyses as they relate to economic impact analysis in support of regulatory impact analysis.

The Importance of Exposure in Addressing Current and Emerging Air Quality Issues

EPA Science Inventory

The air quality issues that we face today and will face in the future are becoming increasingly more complex and require an improved understanding of human exposure to be effectively addressed. The objectives of this paper are (1) to discuss how concepts of human exposure and ex...

[Collaborative study on regulatory science for facilitating clinical development of gene therapy products for genetic diseases].

PubMed

Uchida, Eriko; Igarashi, Yuka; Sato, Yoji

2014-01-01

Gene therapy products are expected as innovative medicinal products for intractable diseases such as life-threatening genetic diseases and cancer. Recently, clinical developments by pharmaceutical companies are accelerated in Europe and the United States, and the first gene therapy product in advanced countries was approved for marketing authorization by the European Commission in 2012. On the other hand, more than 40 clinical studies for gene therapy have been completed or ongoing in Japan, most of them are conducted as clinical researches by academic institutes, and few clinical trials have been conducted for approval of gene therapy products. In order to promote the development of gene therapy products, revision of the current guideline and/or preparation of concept paper to address the evaluation of the quality and safety of gene therapy products are necessary and desired to clearly show what data should be submitted before First-in-Human clinical trials of novel gene therapy products. We started collaborative study with academia and regulatory agency to promote regulatory science toward clinical development of gene therapy products for genetic diseases based on lentivirus and adeno-associated virus vectors; National Center for Child Health and Development (NCCHD), Nippon Medical School and PMDA have been joined in the task force. At first, we are preparing pre-draft of the revision of the current gene therapy guidelines in this project.

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.

Reading handprinted addresses on IRS tax forms

NASA Astrophysics Data System (ADS)

Ramanaprasad, Vemulapati; Shin, Yong-Chul; Srihari, Sargur N.

1996-03-01

The hand-printed address recognition system described in this paper is a part of the Name and Address Block Reader (NABR) system developed by the Center of Excellence for Document Analysis and Recognition (CEDAR). NABR is currently being used by the IRS to read address blocks (hand-print as well as machine-print) on fifteen different tax forms. Although machine- print address reading was relatively straightforward, hand-print address recognition has posed some special challenges due to demands on processing speed (with an expected throughput of 8450 forms/hour) and recognition accuracy. We discuss various subsystems involved in hand- printed address recognition, including word segmentation, word recognition, digit segmentation, and digit recognition. We also describe control strategies used to make effective use of these subsystems to maximize recognition accuracy. We present system performance on 931 address blocks in recognizing various fields, such as city, state, ZIP Code, street number and name, and personal names.

Four essays on offshore wind power potential, development, regulatory framework, and integration

NASA Astrophysics Data System (ADS)

Dhanju, Amardeep

Offshore wind power is an energy resource whose potential in the US has been recognized only recently. There is now growing interest among the coastal states to harness the resource, particularly in states adjacent to the Mid-Atlantic Bight where the shallow continental shelf allows installation of wind turbines using the existing foundation technology. But the promise of bountiful clean energy from offshore wind could be delayed or forestalled due to policy and regulatory challenges. This dissertation is an effort to identify and address some of the important challenges. Focusing on Delaware as a case study it calculates the extent of the wind resource; considers one means to facilitate resource development---the establishment of statewide and regional public power authorities; analyzes possible regulatory frameworks to manage the resource in state-controlled waters; and assesses the use of distributed storage to manage intermittent output from wind turbines. In order to cover a diversity of topics, this research uses a multi-paper format with four essays forming the body of work. The first essay lays out an accessible methodology to calculate offshore wind resource potential using publicly available data, and uses this methodology to access wind resources off Delaware. The assessment suggests a wind resource approximately four times the average electrical load in Delaware. The second essay examines the potential role of a power authority, a quasi-public institution, in lowering the cost of capital, reducing financial risk of developing and operating a wind farm, and enhancing regional collaboration on resource development and management issues. The analysis suggests that a power authority can lower the cost of offshore wind power by as much as 1/3, thereby preserving the ability to pursue cost-competitive development even if the current federal incentives are removed. The third essay addresses the existing regulatory void in state-controlled waters of Delaware

On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

NASA Astrophysics Data System (ADS)

Tarpine, Ryan; Istrail, Sorin

The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

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.

Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

PubMed Central

Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

2011-01-01

Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

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.

Addressing the regulatory and scientific challenges in multiple sclerosis--a statement from the EU regulators.

PubMed

Balabanov, Pavel; Haas, Manuel; Elferink, Andre; Bakchine, Serge; Broich, Karl

2014-09-01

Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document. © The Author(s) 2014.

Regulatory aspects of total product life cycle.

PubMed

Hausman, Ethan D; Altaie, Sousan S

2004-12-01

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

Addressing Emerging Risks: Scientific and Regulatory Challenges Associated with Environmentally Persistent Free Radicals.

PubMed

Dugas, Tammy R; Lomnicki, Slawomir; Cormier, Stephania A; Dellinger, Barry; Reams, Margaret

2016-06-08

Airborne fine and ultrafine particulate matter (PM) are often generated through widely-used thermal processes such as the combustion of fuels or the thermal decomposition of waste. Residents near Superfund sites are exposed to PM through the inhalation of windblown dust, ingestion of soil and sediments, and inhalation of emissions from the on-site thermal treatment of contaminated soils. Epidemiological evidence supports a link between exposure to airborne PM and an increased risk of cardiovascular and pulmonary diseases. It is well-known that during combustion processes, incomplete combustion can lead to the production of organic pollutants that can adsorb to the surface of PM. Recent studies have demonstrated that their interaction with metal centers can lead to the generation of a surface stabilized metal-radical complex capable of redox cycling to produce ROS. Moreover, these free radicals can persist in the environment, hence their designation as Environmentally Persistent Free Radicals (EPFR). EPFR has been demonstrated in both ambient air PM2.5 (diameter < 2.5 µm) and in PM from a variety of combustion sources. Thus, low-temperature, thermal treatment of soils can potentially increase the concentration of EPFR in areas in and around Superfund sites. In this review, we will outline the evidence to date supporting EPFR formation and its environmental significance. Furthermore, we will address the lack of methodologies for specifically addressing its risk assessment and challenges associated with regulating this new, emerging contaminant.

Addressing Emerging Risks: Scientific and Regulatory Challenges Associated with Environmentally Persistent Free Radicals

PubMed Central

Dugas, Tammy R.; Lomnicki, Slawomir; Cormier, Stephania A.; Dellinger, Barry; Reams, Margaret

2016-01-01

Airborne fine and ultrafine particulate matter (PM) are often generated through widely-used thermal processes such as the combustion of fuels or the thermal decomposition of waste. Residents near Superfund sites are exposed to PM through the inhalation of windblown dust, ingestion of soil and sediments, and inhalation of emissions from the on-site thermal treatment of contaminated soils. Epidemiological evidence supports a link between exposure to airborne PM and an increased risk of cardiovascular and pulmonary diseases. It is well-known that during combustion processes, incomplete combustion can lead to the production of organic pollutants that can adsorb to the surface of PM. Recent studies have demonstrated that their interaction with metal centers can lead to the generation of a surface stabilized metal-radical complex capable of redox cycling to produce ROS. Moreover, these free radicals can persist in the environment, hence their designation as Environmentally Persistent Free Radicals (EPFR). EPFR has been demonstrated in both ambient air PM2.5 (diameter < 2.5 µm) and in PM from a variety of combustion sources. Thus, low-temperature, thermal treatment of soils can potentially increase the concentration of EPFR in areas in and around Superfund sites. In this review, we will outline the evidence to date supporting EPFR formation and its environmental significance. Furthermore, we will address the lack of methodologies for specifically addressing its risk assessment and challenges associated with regulating this new, emerging contaminant. PMID:27338429

The impact of parallel regulatory-health technology assessment scientific advice on clinical development. Assessing the uptake of regulatory and health technology assessment recommendations.

PubMed

Tafuri, Giovanni; Lucas, Inês; Estevão, Steve; Moseley, Jane; d'Andon, Anne; Bruehl, Hannah; Gajraj, Elangovan; Garcia, Sonia; Hedberg, Niklas; Massari, Marco; Molina, Andrea; Obach, Mercè; Osipenko, Leeza; Petavy, Frank; Petschulies, Marco; Pontes, Caridad; Russo, Pierluigi; Schiel, Anja; Van de Casteele, Marc; Zebedin-Brandl, Eva-Maria; Rasi, Guido; Vamvakas, Spiros

2018-05-01

The parallel regulatory-health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought. Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed. The development of all clinical studies for which PSA had been sought was tracked using three different databases. The rate of uptake of the advice provided by regulators and HTA bodies was assessed on two key variables: comparator/s and primary endpoint. In terms of uptake of comparator recommendations at the time of PSA in the actual development, our analysis showed that manufacturers implemented comparators to address both the needs of regulators and of at least one HTA body in 12 of 21 studies. For primary endpoints, in all included studies manufacturers addressed both the needs of the regulators and at least one HTA body. One of the key findings of this analysis is that manufacturers tend to implement changes to the development programme based on both regulatory and HTA advice with regards to the choice of primary endpoint and comparator. It also confirms the challenging choice of the study comparator, for which manufacturers seem to be more inclined to satisfy the regulatory advice. Continuous research efforts in this area are of paramount importance from a public health perspective. © 2018 The British Pharmacological Society.

Regulatory immune cells and functions in autoimmunity and transplantation immunology.

PubMed

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

2017-05-01

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

Strategy for Addressing the Retail Sector under the Resource Conservation and Recovery Act's Regulatory Framework

EPA Pesticide Factsheets

The Retail Strategy lays out a cohesive and effective plan to address the unique challenges the retail sector has with complying with the hazardous waste regulations while reducing burden and protecting human health and the environment.

Terms of Address in the Chinese Business Enterprise

ERIC Educational Resources Information Center

Huang, Xiaoyan; Sultan, Robert

2014-01-01

This study examines terms of address currently used by employees of Chinese business enterprises. The authors find that a speaker's address selections are related significantly to the gender of the speaker, the location of the enterprise in Eastern or Western China, and the ownership type of the enterprise; that is, whether the enterprise is…

Widespread Site-Dependent Buffering of Human Regulatory Polymorphism

PubMed Central

Kutyavin, Tanya; Stamatoyannopoulos, John A.

2012-01-01

The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we comprehensively analyzed heritable genome-wide binding patterns of a major sequence-specific regulator (CTCF) in relation to genetic variability in binding site sequences across a multi-generational pedigree. We localized and quantified CTCF occupancy by ChIP-seq in 12 related and unrelated individuals spanning three generations, followed by comprehensive targeted resequencing of the entire CTCF–binding landscape across all individuals. We identified hundreds of variants with reproducible quantitative effects on CTCF occupancy (both positive and negative). While these effects paralleled protein–DNA recognition energetics when averaged, they were extensively buffered by striking local context dependencies. In the significant majority of cases buffering was complete, resulting in silent variants spanning every position within the DNA recognition interface irrespective of level of binding energy or evolutionary constraint. The prevalence of complex partial or complete buffering effects severely constrained the ability to predict reliably the impact of variation within any given binding site instance. Surprisingly, 40% of variants that increased CTCF occupancy occurred at positions of human–chimp divergence, challenging the expectation that the vast majority of functional regulatory variants should be deleterious. Our results suggest that, even in the presence of “perfect” genetic information afforded by resequencing and parallel studies in multiple related individuals, genomic site-specific prediction of the consequences of individual variation in regulatory DNA will require systematic coupling with empirical functional genomic measurements

Research strategies for addressing uncertainties

USGS Publications Warehouse

Busch, David E.; Brekke, Levi D.; Averyt, Kristen; Jardine, Angela; Welling, Leigh; Garfin, Gregg; Jardine, Angela; Merideth, Robert; Black, Mary; LeRoy, Sarah

2013-01-01

Research Strategies for Addressing Uncertainties builds on descriptions of research needs presented elsewhere in the book; describes current research efforts and the challenges and opportunities to reduce the uncertainties of climate change; explores ways to improve the understanding of changes in climate and hydrology; and emphasizes the use of research to inform decision making.

Reading the Tea Leaves: How Utilities in the West Are Managing Carbon Regulatory Risk in their Resource Plans

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

Barbose, Galen; Wiser, Ryan; Phadke, Amol

2008-02-01

The long economic lifetime and development lead-time of many electric infrastructure investments requires that utility resource planning consider potential costs and risks over a lengthy time horizon. One long-term -- and potentially far-reaching -- risk currently facing the electricity industry is the uncertain cost of future carbon dioxide (CO2) regulations. Recognizing the importance of this issue, many utilities (sometimes spurred by state regulatory requirements) are beginning to actively assess carbon regulatory risk within their resource planning processes, and to evaluate options for mitigating that risk. However, given the relatively recent emergence of this issue and the rapidly changing political landscape,more » methods and assumptions used to analyze carbon regulatory risk, and the impact of this analysis on the selection of a preferred resource portfolio, vary considerably across utilities. In this study, we examine the treatment of carbon regulatory risk in utility resource planning, through a comparison of the most-recent resource plans filed by fifteen investor-owned and publicly-owned utilities in the Western U.S. Together, these utilities account for approximately 60percent of retail electricity sales in the West, and cover nine of eleven Western states. This report has two related elements. First, we compare and assess utilities' approaches to addressing key analytical issues that arise when considering the risk of future carbon regulations. Second, we summarize the composition and carbon intensity of the preferred resource portfolios selected by these fifteen utilities and compare them to potential CO2 emission benchmark levels.« less

A Framework for Organizing Current and Future Electric Utility Regulatory and Business Models

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

Satchwell, Andrew; Cappers, Peter; Schwartz, Lisa

In this report, we will present a descriptive and organizational framework for incremental and fundamental changes to regulatory and utility business models in the context of clean energy public policy goals. We will also discuss the regulated utility's role in providing value-added services that relate to distributed energy resources, identify the "openness" of customer information and utility networks necessary to facilitate change, and discuss the relative risks, and the shifting of risks, for utilities and customers.

Therapeutic nucleic acids: current clinical status

PubMed Central

Sridharan, Kannan

2016-01-01

Abstract Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand‐alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics. Several of these compounds are in clinical development and many have received regulatory approval for human use. This review addresses therapeutic uses of DNA based on antisense oligonucleotides, DNA aptamers and gene therapy; and therapeutic uses of RNA including micro RNAs, short interfering RNAs, ribozymes, RNA decoys and circular RNAs. With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise. However, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off‐target toxicity. Technological developments will hold the key to this and help accelerate drug approvals in the years to come. PMID:27111518

Impact of regulatory science on global public health.

PubMed

Patel, Meghal; Miller, Margaret Ann

2012-07-01

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

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

PubMed Central

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

2014-01-01

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

Key anticipated regulatory issues for clinical use of human induced pluripotent stem cells.

PubMed

Knoepfler, Paul S

2012-09-01

The production of human induced pluripotent stem cells (hiPSCs) has greatly expanded the realm of possible stem cell-based regenerative medicine therapies and has particularly exciting potential for autologous therapies. However, future therapies based on hiPSCs will first have to address not only similar regulatory issues as those facing human embryonic stem cells with the US FDA and international regulatory agencies, but also hiPSCs have raised unique concerns as well. While the first possible clinical use of hiPSCs remains down the road, as a field it would be wise for us to anticipate potential roadblocks and begin formulating solutions. In this article, I discuss the potential regulatory issues facing hiPSCs and propose some potential changes in the direction of the field in response.

Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

PubMed

Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

2018-03-22

Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement

Ensuring accountability through health professional regulatory bodies: the case of conflict of interest.

PubMed

Zelisko, Debra; Baumann, Andrea; Gamble, Brenda; Laporte, Audrey; Deber, Raisa B

2014-09-01

How do self-regulated health professions' regulatory bodies address financial conflict of interest (coi) and ensure accountability to the public? using document analysis, we examined how four ontario regulatory colleges (physicians, nurses, physiotherapists, audiologists/speech-language pathologists) defined coi and the education, guidance and enforcement they provided for coi-related issues. These colleges are upholding the mandates to define, identify and address financial coi by providing regulations or standards and guidelines to their membership; they differed in the amount of educational materials provided to their registrants and in the possible coi scenarios they presented. Although there were few disciplinary hearings pertaining to financial coi, findings for the hearings that did occur were documented and posted on the college public registers (the listing of all registered college members along with all relevant practice information), informing the public of any limitations or restrictions placed on a member as a result of the hearing. Copyright © 2014 Longwoods Publishing.

Hydraulic Fracturing Fluid Analysis for Regulatory Parameters - A Progress Report

EPA Pesticide Factsheets

This presentation is a progress report on the analysis of Hydraulic Fracturing Fluids for regulatory compounds outlined in the various US EPA methodologies. Fracturing fluids vary significantly in consistency and viscosity prior to fracturing. Due to the nature of the fluids the analytical challenges will have to be addressed. This presentation also outlines the sampling issues associated with the collection of dissolved gas samples.

Reverse engineering highlights potential principles of large gene regulatory network design and learning.

PubMed

Carré, Clément; Mas, André; Krouk, Gabriel

2017-01-01

Inferring transcriptional gene regulatory networks from transcriptomic datasets is a key challenge of systems biology, with potential impacts ranging from medicine to agronomy. There are several techniques used presently to experimentally assay transcription factors to target relationships, defining important information about real gene regulatory networks connections. These techniques include classical ChIP-seq, yeast one-hybrid, or more recently, DAP-seq or target technologies. These techniques are usually used to validate algorithm predictions. Here, we developed a reverse engineering approach based on mathematical and computer simulation to evaluate the impact that this prior knowledge on gene regulatory networks may have on training machine learning algorithms. First, we developed a gene regulatory networks-simulating engine called FRANK (Fast Randomizing Algorithm for Network Knowledge) that is able to simulate large gene regulatory networks (containing 10 4 genes) with characteristics of gene regulatory networks observed in vivo. FRANK also generates stable or oscillatory gene expression directly produced by the simulated gene regulatory networks. The development of FRANK leads to important general conclusions concerning the design of large and stable gene regulatory networks harboring scale free properties (built ex nihilo). In combination with supervised (accepting prior knowledge) support vector machine algorithm we (i) address biologically oriented questions concerning our capacity to accurately reconstruct gene regulatory networks and in particular we demonstrate that prior-knowledge structure is crucial for accurate learning, and (ii) draw conclusions to inform experimental design to performed learning able to solve gene regulatory networks in the future. By demonstrating that our predictions concerning the influence of the prior-knowledge structure on support vector machine learning capacity holds true on real data ( Escherichia coli K14 network

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

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

PubMed

Johnston, John D; Feldschreiber, Peter

2014-03-01

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

Computational challenges in modeling gene regulatory events.

PubMed

Pataskar, Abhijeet; Tiwari, Vijay K

2016-10-19

Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

Gene Editing: Regulatory and Translation to Clinic.

PubMed

Ando, Dale; Meyer, Kathleen

2017-10-01

The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34 +  hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Matrix addressable vertical cavity surface emitting laser array

NASA Astrophysics Data System (ADS)

Orenstein, M.; von Lehmen, A. C.; Chang-Hasnain, C.; Stoffel, N. G.; Harbison, J. P.

1991-02-01

The design, fabrication and characterization of 1024-element matrix-addressable vertical-cavity surface-emitting laser (VCSEL) arrays are described. A strained InGaAs quantum-well VCSEL structure was grown by MBE, and an array of 32 x 32 lasers was defined using a proton implantation process. A matrix addressing architecture was employed, which enables the individual addressing of each of the 1024 lasers using only 64 electrical contacts. All the lasers in the array, measured after the laser definition step, were operating with fairly homogeneous characteristics; threshold current of 6.8 mA and output quantum differential efficiency of about 8 percent.

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

78 FR 45910 - Proposed Information Collection; Comment Request; Current Population Survey (CPS) Email Address...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

... associated with the multiple personal visits. The email could also be as simple as a ``Thank You'' with... collecting email addresses and collecting interest in being contacted by email or answering the survey...

Are Some Technologies Beyond Regulatory Regimes?

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

Jones, Wendell B.; Kusnezov, Dimitri

Regulatory frameworks are a common tool in governance to incent and coerce behaviors supporting national or strategic stability. This includes domestic regulations and international agreements. Though regulation is always a challenge, the domain of fast evolving threats, like cyber, are proving much more difficult to control. Many discussions are underway searching for approaches that can provide national security in these domains. We use game theoretic learning models to explore the question of strategic stability with respect to the democratization of certain technologies (such as cyber). We suggest that such many-player games could inherently be chaotic with no corresponding (Nash) equilibria.more » In the absence of such equilibria, traditional approaches, as measures to achieve levels of overall security, may not be suitable approaches to support strategic stability in these domains. Altogether new paradigms may be needed for these issues. At the very least, regulatory regimes that fail to address the basic nature of the technology domains should not be pursued as a default solution, regardless of success in other domains. In addition, the very chaotic nature of these domains may hold the promise of novel approaches to regulation.« less

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…

Advances in Behavioral Laboratory Methods that Inform Tobacco Regulatory Science: A TCORS Working Group Special Issue

PubMed Central

Wright, M. Jerry; Valentine, Gerald

2017-01-01

Objective The 2009 Family Smoking Prevention and Tobacco Control Act (TCA) created unprecented enabling conditions for establishing national regulatory policy that reduces the burden of public health and societal problems associated with tobacco product use. The Center for Tobacco Products (CTP), created by the FDA to implement the TCA, developed a first-of-its-kind FDA/National Institutes of Health (NIH) collaborative program to fund Tobacco Centers of Regulatory Science (TCORS). Methods To assist the TCORS with addressing research priorites, working groups (WGs) comprised of FDA-CTP liasions and TCORS investigators were formed. Under the direction of the Center for Evaluation and Coordination of Trainin and Research (CECTR), the TCORS WGs seek to develop tangible work products in their respective areas of focus. Results The focus of the behavioral pharmacology WG evolved from publishing a narrow paper on behavioral methods in electronic cigarette research to a collection of papers on advances in behavioral laboratory methods that may inform tobacco regulatory science. Conclusion This Special Issue contains articles that address all of the CTP research priorities and demonstrates how advances in behavioral laboratory methods made by TCORS investigators can inform FDA efforst to regulate tobacco products. PMID:29152546

Computational challenges in modeling gene regulatory events

PubMed Central

Pataskar, Abhijeet; Tiwari, Vijay K.

2016-01-01

ABSTRACT Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating “omics” data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology. PMID:27390891

78 FR 1624 - Fall 2012 Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

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

E-learning tools for education: regulatory aspects, current applications in radiology and future prospects.

PubMed

Pinto, A; Selvaggi, S; Sicignano, G; Vollono, E; Iervolino, L; Amato, F; Molinari, A; Grassi, R

2008-02-01

E-learning, an abbreviation of electronic learning, indicates the provision of education and training on the Internet or the World Wide Web. The impact of networks and the Internet on radiology is undoubtedly important, as it is for medicine as a whole. The Internet offers numerous advantages compared with other mass media: it provides access to a large amount of information previously known only to individual specialists; it is flexible, permitting the use of images or video; and it allows linking to Web sites on a specific subject, thus contributing to further expand knowledge. Our purpose is to illustrate the regulatory aspects (including Internet copyright laws), current radiological applications and future prospects of e-learning. Our experience with the installation of an e-learning platform is also presented. We performed a PubMed search on the published literature (without time limits) dealing with e-learning tools and applications in the health sector with specific reference to radiology. The search included all study types in the English language with the following key words: e-learning, education, teaching, online exam, radiology and radiologists. The Fiaso study was referred to for the regulatory aspects of e-learning. The application of e-learning to radiology requires the development of a model that involves selecting and creating e-learning platforms, creating and technologically adapting multimedia teaching modules, creating and managing a unified catalogue of teaching modules, planning training actions, defining training pathways and Continuing Education in Medicine (CME) credits, identifying levels of teaching and technological complexity of support tools, sharing an organisational and methodological model, training the trainers, operators' participation and relational devices, providing training, monitoring progress of the activities, and measuring the effectiveness of training. Since 2004, a platform--LiveLearning--has been used at our

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.

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

PubMed

Bonanno, George A; Burton, Charles L

2013-11-01

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

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

PubMed Central

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

2006-01-01

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

Regulatory considerations for 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.

76 FR 67519 - Self-Regulatory Organizations; Fixed Income Clearing Corporation; Notice of Filing of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

... Expand the Applicability of the Fails Charge to Agency Debt Securities Transactions October 26, 2011... the fails charge to Agency debt securities transactions. II. Self-Regulatory Organization's Statement... Federal Reserve Bank of New York (the ``FRBNY''), has been addressing the persistent settlement fails in...

Regulatory Myeloid Cells in Transplantation

PubMed Central

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

2013-01-01

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

Transatlantic Regulatory Cooperation: Background and Analysis

DTIC Science & Technology

2008-10-22

Damien Geradin, “Regulatory Co - opetition ,” Journal of International Economic Law (2000), 235-255, p. 236. 15 Transatlantic Policy Network (TPN), Completing... co -chairs (ministerial-level appointees with cabinet rank) from each side, as well as a number of EU Commissioners and U.S. Cabinet Members for the...broad ranging policy areas covered in the Framework. Currently, the co -chairs are Daniel Price, Assistant to the President for International Economic

Colloid-facilitated radionuclide transport: a regulatory perspective

NASA Astrophysics Data System (ADS)

Dam, W. L.; Pickett, D. A.; Codell, R. B.; Nicholson, T. J.

2001-12-01

What hydrogeologic-geochemical-microbial conditions and processes affect migration of radionuclides sorbed onto microparticles or native colloid-sized radionuclide particles? The U.S. Nuclear Regulatory Commission (NRC) is responsible for protecting public health, safety, and the environment at numerous nuclear facilities including a potential high-level nuclear waste disposal site. To fulfill these obligations, NRC needs to understand the mechanisms controlling radionuclide release and transport and their importance to performance. The current focus of NRC staff reviews and technical interactions dealing with colloid-facilitated transport relates to the potential nuclear-waste repository at Yucca Mountain, Nevada. NRC staff performed bounding calculations to quantify radionuclide releases available for ground-water transport to potential receptors from a Yucca Mountain repository. Preliminary analyses suggest insignificant doses of plutonium and americium colloids could be derived from spent nuclear fuel. Using surface complexation models, NRC staff found that colloids can potentially lower actinide retardation factors by up to several orders of magnitude. Performance assessment calculations, in which colloidal transport of plutonium and americium was simulated by assuming no sorption or matrix diffusion, indicated no effect of colloids on human dose within the 10,000 year compliance period due largely to long waste-package lifetimes. NRC staff have identified information gaps and developed technical agreements with the U.S. Department of Energy (DOE) to ensure sufficient information will be presented in any potential future Yucca Mountain license application. DOE has agreed to identify which radionuclides could be transported via colloids, incorporate uncertainties in colloid formation, release and transport parameters, and conceptual models, and address the applicability of field data using synthetic microspheres as colloid analogs. NRC is currently

Time for a change: addressing R&D and commercialization challenges for antibacterials

PubMed Central

Payne, David J.; Miller, Linda Federici; Findlay, David; Anderson, James; Marks, Lynn

2015-01-01

The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally. PMID:25918443

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

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

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

PubMed

Mathew, Geetha; Unnikrishnan, M K

2015-10-01

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma

PubMed Central

Sun, Jingchun; Gong, Xue; Purow, Benjamin; Zhao, Zhongming

2012-01-01

Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important

78 FR 79721 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-71182; File No. SR-ISE-2013-71] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To More Specifically Address the Number and Size of Contra- Parties to a Qualified Contingent Cross Order December 24, 2013....

Review of the current state of whole slide imaging in pathology

PubMed Central

Pantanowitz, Liron; Valenstein, Paul N.; Evans, Andrew J.; Kaplan, Keith J.; Pfeifer, John D.; Wilbur, David C.; Collins, Laura C.; Colgan, Terence J.

2011-01-01

Whole slide imaging (WSI), or “virtual” microscopy, involves the scanning (digitization) of glass slides to produce “digital slides”. WSI has been advocated for diagnostic, educational and research purposes. When used for remote frozen section diagnosis, WSI requires a thorough implementation period coupled with trained support personnel. Adoption of WSI for rendering pathologic diagnoses on a routine basis has been shown to be successful in only a few “niche” applications. Wider adoption will most likely require full integration with the laboratory information system, continuous automated scanning, high-bandwidth connectivity, massive storage capacity, and more intuitive user interfaces. Nevertheless, WSI has been reported to enhance specific pathology practices, such as scanning slides received in consultation or of legal cases, of slides to be used for patient care conferences, for quality assurance purposes, to retain records of slides to be sent out or destroyed by ancillary testing, and for performing digital image analysis. In addition to technical issues, regulatory and validation requirements related to WSI have yet to be adequately addressed. Although limited validation studies have been published using WSI there are currently no standard guidelines for validating WSI for diagnostic use in the clinical laboratory. This review addresses the current status of WSI in pathology related to regulation and validation, the provision of remote and routine pathologic diagnoses, educational uses, implementation issues, and the cost-benefit analysis of adopting WSI in routine clinical practice. PMID:21886892

Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework.

PubMed

Maeso, Ignacio; Tena, Juan J

2016-09-01

Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

Actual operation and regulatory activities on steam generator replacement in Japan

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

Saeki, Hitoshi

1997-02-01

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

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.

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 Challenges for Cartilage Repair Technologies.

PubMed

McGowan, Kevin B; Stiegman, Glenn

2013-01-01

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

Regulatory Challenges for Cartilage Repair Technologies

PubMed Central

Stiegman, Glenn

2013-01-01

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

Pronouns of Address in Western Ukrainian: Between Tradition and Modernity

ERIC Educational Resources Information Center

Weissenbock, Maria

2006-01-01

This article examines the current usage of terms of address in the Western Ukrainian variety of the Ukrainian language. It investigates the use of pronominal ("ty"--intimate form; ["Vy"--polite, distant form) and nominal forms of address (such as first name, father's name, surname, title, "pan/pani" (Mr/Mrs), "tovarys" (Comrade) etc.) in Western…

GIS-assisted spatial analysis for urban regulatory detailed planning: designer's dimension in the Chinese code system

NASA Astrophysics Data System (ADS)

Yu, Yang; Zeng, Zheng

2009-10-01

By discussing the causes behind the high amendments ratio in the implementation of urban regulatory detailed plans in China despite its law-ensured status, the study aims to reconcile conflict between the legal authority of regulatory detailed planning and the insufficient scientific support in its decision-making and compilation by introducing into the process spatial analysis based on GIS technology and 3D modeling thus present a more scientific and flexible approach to regulatory detailed planning in China. The study first points out that the current compilation process of urban regulatory detailed plan in China employs mainly an empirical approach which renders it constantly subjected to amendments; the study then discusses the need and current utilization of GIS in the Chinese system and proposes the framework of a GIS-assisted 3D spatial analysis process from the designer's perspective which can be regarded as an alternating processes between the descriptive codes and physical design in the compilation of regulatory detailed planning. With a case study of the processes and results from the application of the framework, the paper concludes that the proposed framework can be an effective instrument which provides more rationality, flexibility and thus more efficiency to the compilation and decision-making process of urban regulatory detailed plan in China.

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

78 FR 16733 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69114; File No. SR-ISE-2013-18] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change To Address Order Handling Under the Options Order Protection and Locked/Crossed Market Plan, the Authority of the Exchange To Cancel Orders When a...

77 FR 70517 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68262; File No. SR-CBOE-2012-108] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed Rule Change To Address Authority To Cancel Orders When a Technical or Systems Issue Occurs and To Describe the Operation of Routing Service Error Accounts November 19...

77 FR 70511 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68265; File No. SR-CBOE-2012-109] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Proposed Rule Change Related to CBSX To Address Authority To Cancel Orders When a Technical or Systems Issue Occurs and To Describe the Operation of Routing Service Error...

Protection of people and environment from radiation risk through good regulatory practice

NASA Astrophysics Data System (ADS)

Jais, Azlina Mohammad; Hassan, Najwa

2017-01-01

The term "good regulatory practice" has seen growing frequency of usage worldwide, especially since the 2011 Fukushima nuclear incident. However, the term appears quite ambiguous as it may mean differently to different people. This leads us to the first important question: what does "good regulatory practice" actually mean? When used in conjunction with the Fukushima incident, do we imply that there is an absence of "good regulatory practice" in the Japanese' Nuclear and Industry Safety Agency (NISA)? This is quite troubling. It is clear that the term should be defined formally so that our understanding of "good regulatory practice" can be standardized. There is still another important question beyond agreeing on what "good regulatory practice" is: is "good regulatory practice" specific to a region, or is it global? And is it applicable only to nuclear regulators, or to all types of regulators per se? This paper aims to deliberate on the above mentioned questions. Specifically, we hope to discuss the "good regulatory practice" for atomic energy activities in order to protect the people and the environment from radiation risk of such activities. By understanding what "good regulatory practice" truly means, a newcomer country such as Malaysia can quickly learn and adopt these practices so as to assure a competent national nuclear regulatory authority who will be responsible in ensuring the safety, security and safeguards of peaceful atomic energy activities in the country including nuclear liability. In understanding this concept, a holistic approach will be taken by looking into example of advanced and newcomer countries of various nuclear regulatory authorities all around the world. Then the paper will focus on the challenges that the current nuclear regulatory authority in Malaysia which is Atomic Energy Licensing Board has, its challenges to follow the concept of "good regulatory practice" and its ways to overcome it. This study explore the initiatives could be

CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

PubMed

Jamieson, Catriona H M; Millan, Maria T; Creasey, Abla A; Lomax, Geoff; Donohoe, Mary E; Walters, Mark C; Abedi, Mehrdad; Bota, Daniela A; Zaia, John A; Adams, John S

2018-06-01

The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges. Copyright © 2018 Elsevier Inc. All rights reserved.

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...

Operationalizing Dynamic Ocean Management (DOM): Understanding the Incentive Structure, Policy and Regulatory Context for DOM in Practice

NASA Astrophysics Data System (ADS)

Lewison, R. L.; Saumweber, W. J.; Erickson, A.; Martone, R. G.

2016-12-01

Dynamic ocean management, or management that uses near real-time data to guide the spatial distribution of commercial activities, is an emerging approach to balance ocean resource use and conservation. Employing a wide range of data types, dynamic ocean management in a fisheries context can be used to meet multiple objectives - managing target quota, bycatch reduction, and reducing interactions with species of conservation concern. There is a growing list of DOM applications currently in practice in fisheries around the world, yet the approach is new enough that both fishers and fisheries managers are unclear how DOM can be applied to their fishery. Here, we use the experience from dynamic ocean management applications that are currently in practice to address the commonly asked question "How can dynamic management approaches be implemented in a traditionally managed fishery?". Combining knowledge from the DOM participants with a review of regulatory frameworks and incentive structures, stakeholder participation, and technological requirements of DOM in practice, we identify ingredients that have supported successful implementation of this new management approach.

Genomic identification of regulatory elements by evolutionary sequence comparison and functional analysis.

PubMed

Loots, Gabriela G

2008-01-01

Despite remarkable recent advances in genomics that have enabled us to identify most of the genes in the human genome, comparable efforts to define transcriptional cis-regulatory elements that control gene expression are lagging behind. The difficulty of this task stems from two equally important problems: our knowledge of how regulatory elements are encoded in genomes remains elementary, and there is a vast genomic search space for regulatory elements, since most of mammalian genomes are noncoding. Comparative genomic approaches are having a remarkable impact on the study of transcriptional regulation in eukaryotes and currently represent the most efficient and reliable methods of predicting noncoding sequences likely to control the patterns of gene expression. By subjecting eukaryotic genomic sequences to computational comparisons and subsequent experimentation, we are inching our way toward a more comprehensive catalog of common regulatory motifs that lie behind fundamental biological processes. We are still far from comprehending how the transcriptional regulatory code is encrypted in the human genome and providing an initial global view of regulatory gene networks, but collectively, the continued development of comparative and experimental approaches will rapidly expand our knowledge of the transcriptional regulome.

75 FR 2170 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... addresses BX Rule 2240 entitled ``Disclosure of Control Relationship with Issuer'' and 2250 entitled... reference to NASD 2240 [sic] entitled ``Disclosure of Control Relationship with Issuer.'' The Commission... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61298; File No. SR-BX-2009-087] Self-Regulatory...

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.

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions.

PubMed

Ogbogu, Ubaka; Burningham, Sarah; Ollenberger, Adam; Calder, Kathryn; Du, Li; El Emam, Khaled; Hyde-Lay, Robyn; Isasi, Rosario; Joly, Yann; Kerr, Ian; Malin, Bradley; McDonald, Michael; Penney, Steven; Piat, Gayle; Roy, Denis-Claude; Sugarman, Jeremy; Vercauteren, Suzanne; Verhenneman, Griet; West, Lori; Caulfield, Timothy

2014-02-03

The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors' clinical information for research and regulatory purposes, and existing practices that limit research participants' ability to control what is done with their genetic data, amplify the privacy concerns. To date, the privacy issues associated with cell-based research and interventions have not received much attention in the academic and policymaking contexts. This paper, arising out of a multi-disciplinary workshop, aims to rectify this by outlining the issues, proposing novel governance strategies and policy recommendations, and identifying areas where further evidence is required to make sound policy decisions. The authors of this paper take the position that existing rules and norms can be reasonably extended to address privacy risks in this context without compromising emerging developments in the research environment, and that exceptions from such rules should be justified using a case-by-case approach. In developing new policies, the broader framework of regulations governing cell-based research and related areas must be taken into account, as well as the views of impacted groups, including scientists, research participants and the general public. This paper outlines deliberations at a policy development workshop focusing on privacy challenges associated with cell-based research and interventions. The paper provides an overview of these challenges, followed by a discussion of key themes and recommendations that emerged from discussions at the workshop. The paper concludes that privacy risks associated with cell

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions

PubMed Central

2014-01-01

Background The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors’ clinical information for research and regulatory purposes, and existing practices that limit research participants’ ability to control what is done with their genetic data, amplify the privacy concerns. Discussion To date, the privacy issues associated with cell-based research and interventions have not received much attention in the academic and policymaking contexts. This paper, arising out of a multi-disciplinary workshop, aims to rectify this by outlining the issues, proposing novel governance strategies and policy recommendations, and identifying areas where further evidence is required to make sound policy decisions. The authors of this paper take the position that existing rules and norms can be reasonably extended to address privacy risks in this context without compromising emerging developments in the research environment, and that exceptions from such rules should be justified using a case-by-case approach. In developing new policies, the broader framework of regulations governing cell-based research and related areas must be taken into account, as well as the views of impacted groups, including scientists, research participants and the general public. Summary This paper outlines deliberations at a policy development workshop focusing on privacy challenges associated with cell-based research and interventions. The paper provides an overview of these challenges, followed by a discussion of key themes and recommendations that emerged from discussions at the workshop. The paper concludes that

Multiscale Modeling in Computational Biomechanics: Determining Computational Priorities and Addressing Current Challenges

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

Tawhai, Merryn; Bischoff, Jeff; Einstein, Daniel R.

2009-05-01

Abstract In this article, we describe some current multiscale modeling issues in computational biomechanics from the perspective of the musculoskeletal and respiratory systems and mechanotransduction. First, we outline the necessity of multiscale simulations in these biological systems. Then we summarize challenges inherent to multiscale biomechanics modeling, regardless of the subdiscipline, followed by computational challenges that are system-specific. We discuss some of the current tools that have been utilized to aid research in multiscale mechanics simulations, and the priorities to further the field of multiscale biomechanics computation.

Assessing the relevance of ecotoxicological studies for regulatory decision making.

PubMed

Rudén, Christina; Adams, Julie; Ågerstrand, Marlene; Brock, Theo Cm; Poulsen, Veronique; Schlekat, Christian E; Wheeler, James R; Henry, Tala R

2017-07-01

Regulatory policies in many parts of the world recognize either the utility of or the mandate that all available studies be considered in environmental or ecological hazard and risk assessment (ERA) of chemicals, including studies from the peer-reviewed literature. Consequently, a vast array of different studies and data types need to be considered. The first steps in the evaluation process involve determining whether the study is relevant to the ERA and sufficiently reliable. Relevance evaluation is typically performed using existing guidance but involves application of "expert judgment" by risk assessors. In the present paper, we review published guidance for relevance evaluation and, on the basis of the practical experience within the group of authors, we identify additional aspects and further develop already proposed aspects that should be considered when conducting a relevance assessment for ecotoxicological studies. From a regulatory point of view, the overarching key aspect of relevance concerns the ability to directly or indirectly use the study in ERA with the purpose of addressing specific protection goals and ultimately regulatory decision making. Because ERA schemes are based on the appropriate linking of exposure and effect estimates, important features of ecotoxicological studies relate to exposure relevance and biological relevance. Exposure relevance addresses the representativeness of the test substance, environmental exposure media, and exposure regime. Biological relevance deals with the environmental significance of the test organism and the endpoints selected, the ecological realism of the test conditions simulated in the study, as well as a mechanistic link of treatment-related effects for endpoints to the protection goal identified in the ERA. In addition, uncertainties associated with relevance should be considered in the assessment. A systematic and transparent assessment of relevance is needed for regulatory decision making. The relevance

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

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

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

PubMed

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

2017-08-01

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

Creating and testing regulatory focus messages to enhance medication adherence.

PubMed

O'Connor, Ashley; Ladebue, Amy; Peterson, Jamie; Davis, Ryan; Jung Grant, Susan; McCreight, Marina; Lambert-Kerzner, Anne

2018-01-01

Objectives Strategies were explored to improve patient adherence to cardioprotective medications by borrowing from a motivational framework used in psychology, regulatory focus theory. The current study is part of a larger randomized control trial and was aimed at understanding what written educational messages, based on patients' regulatory focus tendency, resonated with each individual as a potential reminder to take medications. This study was also aimed at understanding why messages resonated with the patients. Methods Twenty veterans were tested for regulatory fitand presented with messages dependent on focus tendency. In-person semi-structured interviews were conducted to collect feedback of messages. An iterative analysis drawing primarily on matrix and reflexive team analyses was conducted. Result Six promotion and six prevention messages emerged, such as "team up with your provider to create a combination of medications to prevent illness" and "Live your best life - Take your medications". Five themes related to types of health messages that spoke to patients' regulatory fit were discovered: relatability; empowerment and control; philosophy on life; relationship with provider and medications; and vocabulary effect on the impact of messages. Discussion Motivational messages based on regulatory fit may be useful in improving patient medication adherence, leading to improved cardiovascular outcomes.

Current Status of On-Site Wastewater Management

ERIC Educational Resources Information Center

Senn, Charles L.

1978-01-01

Wastewater management is becoming an important environmental issue nationally. This article reports the history and current status of wastewater management. Regulatory programs are discussed with specific state examples. Needs assessment is also included. (MA)

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

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

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

PubMed

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

2014-11-21

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

Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

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

Integrated Communications, Navigation and Surveillance Technologies Keynote Address

NASA Technical Reports Server (NTRS)

Lebacqz, J. Victor

2004-01-01

Slides for the Keynote Address present graphics to enhance the discussion of NASA's vision, the National Space Exploration Initiative, current Mars exploration, and aeronautics exploration. The presentation also focuses on development of an Air Transportation System and transformation from present systems.

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

[Regulatory T cells].

PubMed

Marinić, Igor; Gagro, Alenka; Rabatić, Sabina

2006-12-01

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

Food irradiation—US regulatory considerations

NASA Astrophysics Data System (ADS)

Morehouse, Kim M.

2002-03-01

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

The current status of NORM/TENORM industries and establishment of regulatory framework in Korea.

PubMed

Chang, Byung-Uck; Kim, Yongjae; Oh, Jang-Jin

2011-07-01

During the last several years, a nationwide survey on naturally occurring radioactive material (NORM)/technologically enhanced naturally occurring radioactive materials (TENORM) industries has been conducted. Because of the rapid economic growth in Korea, the huge amount of raw materials, including NORM have been consumed in various industrial areas, and some representative TENORM industries exist in Korea. Recently, the Korean government decided to establish a regulatory framework for natural radiation, including NORM/TENORM and is making efforts to introduce relevant publically consent regulations on the basis of international safety standards.

Memory Compression Techniques for Network Address Management in MPI

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

Guo, Yanfei; Archer, Charles J.; Blocksome, Michael

MPI allows applications to treat processes as a logical collection of integer ranks for each MPI communicator, while internally translating these logical ranks into actual network addresses. In current MPI implementations the management and lookup of such network addresses use memory sizes that are proportional to the number of processes in each communicator. In this paper, we propose a new mechanism, called AV-Rankmap, for managing such translation. AV-Rankmap takes advantage of logical patterns in rank-address mapping that most applications naturally tend to have, and it exploits the fact that some parts of network address structures are naturally more performance criticalmore » than others. It uses this information to compress the memory used for network address management. We demonstrate that AV-Rankmap can achieve performance similar to or better than that of other MPI implementations while using significantly less memory.« less

Trans‐acting translational regulatory RNA binding proteins

PubMed Central

Harvey, Robert F.; Smith, Tom S.; Mulroney, Thomas; Queiroz, Rayner M. L.; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa

2018-01-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans‐acting regulatory RNA‐binding proteins (RBPs) are necessary to provide mRNA‐specific translation, and these interact with 5′ and 3′ untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans‐acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans‐acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans‐acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: 1RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes2Translation > Translation Regulation3Translation > Translation Mechanisms PMID:29341429

Time for a change: addressing R&D and commercialization challenges for antibacterials.

PubMed

Payne, David J; Miller, Linda Federici; Findlay, David; Anderson, James; Marks, Lynn

2015-06-05

The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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.

Influence of Natural American Spirit advertising on current and former smokers' perceptions and intentions.

PubMed

Gratale, Stefanie K; Maloney, Erin K; Sangalang, Angeline; Cappella, Joseph N

2017-10-21

This study sought to demonstrate causal effects of exposure to Natural American Spirit (NAS) advertising content on misinformed beliefs of current and former smokers, and to empirically establish these beliefs as a mechanism driving intentions to use NAS. Our study employed a randomised experimental design with 1128 adult daily, intermittent and former smokers. We compared participants who were exposed to NAS advertisements or claims made in the advertisements with those in a no-message control group to test the effects of NAS advertising content on inaccurate beliefs about NAS and attitudes and intentions towards the product. One-way analysis of variance revealed that exposure to NAS advertisements produced inaccurate beliefs about the composition of NAS cigarettes among current and former smokers (p<0.05). Planned contrasts indicated a compilation of arguments taken directly from NAS advertisements resulted in significantly greater beliefs that NAS cigarettes are healthier/safer than other cigarettes (for former smokers, t(472)=3.63, p<0.001; for current smokers, t(644)=2.86, p=0.004), demonstrating that suggestive claims used in the brand's marketing have effects on beliefs not directly addressed in the advertisements. Regression and mediation analyses showed that health-related beliefs predict attitudes towards NAS for current and former smokers, and mediate intentions to use NAS. The findings of this study provide causal support for the need for further regulatory action to address the potentially harmful ramifications of claims used in NAS advertising. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Emerging regulatory paradigms in glutathione metabolism

PubMed Central

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

2015-01-01

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

Regulatory Scientific Advice on Non-Inferiority Drug Trials

PubMed Central

Knol, Mirjam J.; Klungel, Olaf H.; Gispen-De Wied, Christine C.; de Boer, Antonius; Hoes, Arno W.; Leufkens, Hubert G.; Mantel-Teeuwisse, Aukje K.

2013-01-01

The active-controlled trial with a non-inferiority design has gained popularity in recent years. However, non-inferiority trials present some methodological challenges, especially in determining the non-inferiority margin. Regulatory guidelines provide some general statements on how a non-inferiority trial should be conducted. Moreover, in a scientific advice procedure, regulators give companies the opportunity to discuss critical trial issues prior to the start of the trial. The aim of this study was to identify potential issues that may benefit from more explicit guidance by regulators. To achieve this, we collected and analyzed questions about non-inferiority trials posed by applicants for scientific advice in Europe in 2008 and 2009, as well as the responses given by the European Medicines Agency (EMA). In our analysis we included 156 final letters of advice from 2008 and 2009, addressed to 94 different applicants (manufacturers). Our analysis yielded two major findings: (1) applicants frequently asked questions ‘whether’ and ‘how’ to conduct a non-inferiority trial, 26% and 74%, respectively, and (2) the EMA regulators seem mainly concerned about the choice of the non-inferiority margin in non-inferiority trials (36% of total regulatory answers). In 40% of the answers, the EMA recommended using a stricter margin, and in 10% of the answers regarding non-inferiority margins, the EMA questioned the justification of the proposed non-inferiority margin. We conclude that there are still difficulties in selecting the appropriate methodology for non-inferiority trials. Straightforward and harmonized guidance regarding non-inferiority trials is required, for example on whether it is necessary to conduct such a trial and how the non-inferiority margin is determined. It is unlikely that regulatory guidelines can cover all therapeutic areas; therefore, in some cases regulatory scientific advice may be used as an opportunity for tailored advice. PMID:24040346

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

PubMed

Rhodes, Linda

2018-05-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

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

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

PubMed

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S; Campbell, Iain C; Schmidt, Ulrike

2017-01-01

Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

78 FR 79718 - Self-Regulatory Organizations; Topaz Exchange, LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-71181; File No. SR-Topaz-2013-19] Self-Regulatory Organizations; Topaz Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to More Specifically Address the Number and Size of Contra-parties to a Qualified Contingent Cross Order December 24, 2014. Pursuant to...

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…

MODEL EVALUATION SCIENCE TO MEET TODAY'S QUALITY ASSURANCE REQUIREMENTS FOR REGULATORY USE: ADDRESSING UNCERTAINTY, SENSITIVITY, AND PARAMETERIZATION

EPA Science Inventory

The EPA/ORD National Exposure Research Lab's (NERL) UA/SA/PE research program addresses both tactical and strategic needs in direct support of ORD's client base. The design represents an integrated approach in achieving the highest levels of quality assurance in environmental de...

77 FR 73705 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... Amending Rule 472-- Equities, Which Addresses Communications With the Public, Adopting New Rule Text To... text to conform to the changes adopted by the Financial Industry Regulatory Authority, Inc. (``FINRA... ``JOBS Act'').\\4\\ The text of the proposed rule change is available on the Exchange's Web site at www...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

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

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

PubMed

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

2012-03-01

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

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.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the By- Laws of FINRA Regulation, Inc. With Regard to District Committees April 28, 2011. I. Introduction On February 25, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

Regulatory scientific advice in drug development: does company size make a difference?

PubMed Central

Putzeist, Michelle; Gispen-De Wied, Christine C.; Hoes, Arno W.; Leufkens, Hubert G.

2010-01-01

Purpose To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. Methodology A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006–2008. Definition of company size was based on ranking by total revenues (Scrip’s Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). Results In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). Conclusion The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development. PMID:21049297

Regulatory scientific advice in drug development: does company size make a difference?

PubMed

Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G

2011-02-01

To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006-2008. Definition of company size was based on ranking by total revenues (Scrip's Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development.

75 FR 6422 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Incorporated NYSE Rule 411(a)(ii)(5) as Part of the Process of Developing the Consolidated FINRA Rulebook February 2, 2010. On December 4, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

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.

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas.

PubMed

Sousa, Varley Dias; Ramalho, Pedro I; Silveira, Dâmaris

2016-05-01

Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

Maternal Prenatal Stress and Infant Regulatory Capacity in Mexican Americans

PubMed Central

Lin, Betty; Crnic, Keith A.; Luecken, Linda J.; Gonzales, Nancy A.

2014-01-01

The early postpartum period lays important groundwork for later self-regulation as infants' dispositional traits interact with caregivers' co-regulatory behaviors to produce the earliest forms of self-regulation. Although emerging literature suggests that fetal exposure to maternal stress may be integral in determining child self-regulatory capacity, the complex pathways that characterize these early developmental processes remain unclear. The current study considers these complex, transactional processes in a low income, Mexican American sample. Data were collected from 295 Mexican American infants and their mothers during prenatal, 6- and 12-week postpartum home interviews. Mother reports of stress were obtained prenatally, and mother reports of infant temperament were obtained at 6 weeks. Observer ratings of maternal sensitivity and infant regulatory behaviors were obtained at the 6- and 12-week time points. Study results indicate that prenatal stress predicts higher levels of infant negativity and surgency, both of which directly or interactively predict later engagement in regulatory behaviors. Unexpectedly, prenatal stress also predicted more engagement in orienting, but not self-comforting behaviors. Advancing understandings about the nature of these developmental pathways may have significant implications for targets of early intervention in this high risk population. PMID:25113917

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

PubMed Central

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

2013-01-01

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

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.

Addressing Prediabetes in Childhood Obesity Treatment Programs: Support from Research and Current Practice

PubMed Central

Grow, H. Mollie; Fernandez, Cristina; Lukasiewicz, Gloria J.; Rhodes, Erinn T.; Shaffer, Laura A.; Sweeney, Brooke; Woolford, Susan J.; Estrada, Elizabeth

2014-01-01

Abstract Background: Type 2 diabetes mellitus (T2DM) and prediabetes have increased in prevalence among overweight and obese children, with significant implications for long-term health. There is little published evidence on the best approaches to care of prediabetes among overweight youth or the current practices used across pediatric weight management programs. Methods: This article reviews the literature and summarizes current practices for screening, diagnosis, and treatment of prediabetes at childhood obesity treatment centers. Findings regarding current practice were based on responses to an online survey from 28 pediatric weight management programs at 25 children's hospitals in 2012. Based on the literature reviewed, and empiric data, consensus support statements on prediabetes care and T2DM prevention were developed among representatives of these 25 children's hospitals' obesity clinics. Results: The evidence reviewed demonstrates that current T2DM and prediabetes diagnostic parameters are derived from adult-based studies with little understanding of clinical outcomes among youth. Very limited evidence exists on preventing progression of prediabetes. Some evidence suggests that a significant proportion of obese youth with prediabetes will revert to normoglycemia without pharmacological management. Evidence supports lifestyle modification for children with prediabetes, but further study of specific lifestyle changes and pharmacological treatments is needed. Conclusion: Evidence to guide management of prediabetes in children is limited. Current practice patterns of pediatric weight management programs show areas of variability in practice, reflecting the limited evidence base. More research is needed to guide clinical care for overweight youth with prediabetes. PMID:25055134

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...

12 CFR 562.2 - Regulatory reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

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.

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.

The Chinese health care regulatory institutions in an era of transition.

PubMed

Fang, Jing

2008-02-01

The purpose of this paper is to contribute to a better understanding of Chinese health care regulation in an era of transition. It describes the major health care regulatory institutions operating currently in China and analyzes the underlying factors. The paper argues that in the transition from a planned to a market economy, the Chinese government has been employing a hybrid approach where both old and new institutions have a role in the management of emerging markets, including the health care market. This approach is consistent with the incremental reform strategy adopted by the Party-state. Although a health care regulatory framework has gradually taken shape, the framework is incomplete, with a particular lack of emphasis on professional self-regulation. In addition, its effectiveness is limited despite the existence of many regulatory institutions. In poor rural areas, the effectiveness of the regulatory framework is further undermined or distorted by the extremely difficult financial position that local governments find themselves in. The interpretations of the principle of 'rule of law' by policy makers and officials at different levels and the widespread informal network of relations between known individuals (Guanxi) play an important role in the operation of the regulatory framework. The findings of this paper reveal the complex nature of regulating health care in transitional China.

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.

75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA...) (SEC Approves Consolidated FINRA Rules Governing Financial Responsibility). FINRA announced in...

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…

Regulatory Dendritic Cells.

PubMed

Sato, Katsuaki; Uto, Tomofumi; Fukaya, Tomohiro; Takagi, Hideaki

2017-01-01

Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines. On the other hand, treatment of DCs with certain immunosuppressive drugs and molecules leads to the generation of tolerogenic DCs that show downregulation of both the major histocompatibility complex (MHC) and costimulatory molecules, and not only show defective T-cell activation, but also possess tolerogenic properties including the induction of anergic T-cells and regulatory T (T reg ) cells. To develop an effective strategy for Ag-specific intervention of T-cell-mediated immune disorders, we have previously established the modified DCs with moderately high levels of MHC molecules that are defective in the expression of costimulatory molecules that had a greater immunoregulatory property than classical tolerogenic DCs, which we therefore designated as regulatory DCs (DC reg ). Herein, we integrate the current understanding of the role of DCs in the control of immune responses, and further provide new information of the characteristics of tolerogenic DCs and DC reg , as well as their regulation of immune responses and disorders.

Trans-acting translational regulatory RNA binding proteins.

PubMed

Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

2018-05-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.

A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

PubMed

Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

2018-06-30

In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

The effect of regulatory mode on procrastination: Bi-stable parahippocampus connectivity with dorsal anterior cingulate and anterior prefrontal cortex.

PubMed

Zhang, Chenyan; Ni, Yan; Feng, Tingyong

2017-06-30

Previous research has elucidated that procrastination can be influenced by regulatory mode orientations. However, the neural mechanism of regulatory modes affecting procrastination is not well understood. To address this question, we employed resting-state functional magnetic resonance imaging (RS-fMRI) to test the influence of two regulatory modes (assessment and locomotion) on procrastination. The behavioral results showed that procrastination was positively correlated with assessment orientation but negatively correlated with locomotion orientation. Neuroimaging results indicated that the functional connectivity between parahippocampal cortex (PHC) and dorsal anterior cingulate (dACC) was negatively correlated with assessment scores, while the functional connectivity between anterior prefrontal cortex (aPFC) and parahippocampal cortex (PHC) was negatively correlated with locomotion scores. Critically, mediation analysis showed that the different effects of two distinct regulatory modes on procrastination were mediated by PHC-dACC and aPFC-PHC functional connectivity respectively. These results suggested that people's procrastination could be predicted by regulatory mode orientations, which is mediated by PHC connectivity with dACC and aPFC respectively. The present study extends our knowledge on procrastination and provides neural mechanism for understanding the link between regulatory mode orientations and procrastination. Copyright © 2017. Published by Elsevier B.V.

76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

Detection of Spoofed MAC Addresses in 802.11 Wireless Networks

NASA Astrophysics Data System (ADS)

Tao, Kai; Li, Jing; Sampalli, Srinivas

Medium Access Control (MAC) address spoofing is considered as an important first step in a hacker's attempt to launch a variety of attacks on 802.11 wireless networks. Unfortunately, MAC address spoofing is hard to detect. Most current spoofing detection systems mainly use the sequence number (SN) tracking technique, which has drawbacks. Firstly, it may lead to an increase in the number of false positives. Secondly, such techniques cannot be used in systems with wireless cards that do not follow standard 802.11 sequence number patterns. Thirdly, attackers can forge sequence numbers, thereby causing the attacks to go undetected. We present a new architecture called WISE GUARD (Wireless Security Guard) for detection of MAC address spoofing on 802.11 wireless LANs. It integrates three detection techniques - SN tracking, Operating System (OS) fingerprinting & tracking and Received Signal Strength (RSS) fingerprinting & tracking. It also includes the fingerprinting of Access Point (AP) parameters as an extension to the OS fingerprinting for detection of AP address spoofing. We have implemented WISE GUARD on a test bed using off-the-shelf wireless devices and open source drivers. Experimental results show that the new design enhances the detection effectiveness and reduces the number of false positives in comparison with current approaches.

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

PubMed Central

Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

2006-01-01

Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to

77 FR 57621 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

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2010-02-04

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76 FR 32246 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2011-06-03

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76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2011-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

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

EPA leadership on Science, Innovation, and Decision Support Tools for Addressing Current and Future Challenges

EPA Science Inventory

When the U.S. Environmental Protection Agency (EPA) was established nearly 50 years ago, the nation faced serious threats to its air, land, and water, which in turn impacted human health. These threats were effectively addressed by the creation of EPA (in 1970) and many subsequen...

PURPA: The intersection of competition and regulatory policy

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

Cudahy, R.D.

High on the priority list of matters to be considered by Congress is the reform and possible repeal of section 210 of the Public Utility Regulatory Policies Act of 1978 (PURPA). The values addressed by PURPA are as important today as they were when the legislation was adopted in 1978. This is true even if plans for competition have moved beyond PURPA. No doubt a large part of the generation added in the last fifteen years meets the PURPA objectives. A palusible - but unconvincing - case can therefore be made for reforming PURPA by restricting benefits to alternative energymore » projects, or even foreliminating the PURPA preference entirely. This sort of radical surgery, unless PURPA is supplanted by some equally effective regulatory scheme, will likely result in a major downgrading of PURPA`s primary objectives. However the chips may fall, the essential PURPA objectives - energy conservation and diversification of generating resources - are as worthy today as they were when the statute was enacted. Modifications of PURPA may be in order, and reexamination by the FERC and by Congress may be necessary. This ought not, however, involve abandonment of PURPA`s basic policy objectives.« less

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial

PubMed Central

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S.; Campbell, Iain C.; Schmidt, Ulrike

2017-01-01

Background Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. Objective This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Methods Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. Results AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. Conclusions These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN. PMID:28121991

77 FR 39313 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2012-07-02

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...,\\2\\ notice is hereby given that on June 26, 2012, Financial Industry Regulatory Authority, Inc..., as FINRA shall designate, to file such additional financial or operational schedules or reports as...

77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2012-02-10

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

76 FR 55441 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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2011-09-07

... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory... significant aspects of such statements. A. Self-Regulatory Organization's Statement of the Purpose of, and... professional responsibilities, including key regulatory and control themes, as well as the importance of...

Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.

PubMed

Murray, Heath; Koh, Alan

2014-10-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes.

Establishing a laboratory animal model from a transgenic animal: RasH2 mice as a model for carcinogenicity studies in regulatory science.

PubMed

Urano, K; Tamaoki, N; Nomura, T

2012-01-01

Transgenic animal models have been used in small numbers in gene function studies in vivo for a period of time, but more recently, the use of a single transgenic animal model has been approved as a second species, 6-month alternative (to the routine 2-year, 2-animal model) used in short-term carcinogenicity studies for generating regulatory application data of new drugs. This article addresses many of the issues associated with the creation and use of one of these transgenic models, the rasH2 mouse, for regulatory science. The discussion includes strategies for mass producing mice with the same stable phenotype, including constructing the transgene, choosing a founder mouse, and controlling both the transgene and background genes; strategies for developing the model for regulatory science, including measurements of carcinogen susceptibility, stability of a large-scale production system, and monitoring for uniform carcinogenicity responses; and finally, efficient use of the transgenic animal model on study. Approximately 20% of mouse carcinogenicity studies for new drug applications in the United States currently use transgenic models, typically the rasH2 mouse. The rasH2 mouse could contribute to animal welfare by reducing the numbers of animals used as well as reducing the cost of carcinogenicity studies. A better understanding of the advantages and disadvantages of the transgenic rasH2 mouse will result in greater and more efficient use of this animal model in the future.

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders? 120.463 Section 120.463 Business....463 Regulatory accounting—What are SBA's regulatory accounting requirements for SBA Supervised Lenders...

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2013-10-02

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Approaches to Understanding and Addressing Treatment-Resistant Depression: A Scoping Review

PubMed Central

Jenkins, Emily; Goldner, Elliot M.

2012-01-01

Treatment-resistant depression is associated with significant disability and, due to its high prevalence, results in substantive economic and societal burden at a population level. The objective of this study is to synthesize extant literature on approaches currently being applied to understand and address this condition. It is hoped that the findings can be used to inform practitioners and guide future research. A scoping review of the scientific literature was conducted with findings categorized and charted by underlying research paradigm. Currently, the vast majority of research stems from a biological paradigm (81%). Research on treatment-resistant depression would benefit from a broadened field of study. Given that multiple etiological mechanisms likely contribute to treatment-resistant depression and current efforts at prevention and treatment have substantial room for improvement, an expanded research agenda could more effectively address this significant public health issue. PMID:22570778

IFN-α and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells

PubMed Central

Le Buanec, Hélène; Gougeon, Marie-Lise; Mathian, Alexis; Lebon, Pierre; Dupont, Jean-Michel; Peltre, Gabriel; Hemon, Patrice; Schmid, Michel; Bizzini, Bernard; Künding, Thomas; Burny, Arsène; Bensussan, Armand; Amoura, Zahir; Gallo, Robert C.; Zagury, Daniel

2011-01-01

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10–secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-α. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-α and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti–IFN-α Ab immunotherapy in lupus patients. PMID:22065791

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

PubMed Central

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

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.

Implications for current regulatory waste toxicity characterisation methods from analysing metal and metalloid leaching from photovoltaic modules

NASA Astrophysics Data System (ADS)

Collins, Mary Kayla; Anctil, Annick

2017-07-01

The appropriateness of regulatory methods to characterise the toxicity of photovoltaic (PV) modules was investigated to quantify potential environmental impacts for modules disposed of in landfills. Because solar energy is perceived as a green technology, it is important to ensure that end-of-life issues will not be detrimental to solar energy's success. United States Environmental Protection Agency Method 1311, California waste extraction test, and modified versions of both were performed on a multi-crystalline silicon module and cells and a copper indium gallium diselenide (CIGS) module. Variations in metal leachate concentrations were found with changes in testing parameters. Lead concentrations from the multi-crystalline module ranged from 16.2 to 50.2 mg/L. Cadmium concentrations from the CIGS module ranged from 0.1 to 3.52 mg/L. This raises doubt that regulatory methods can adequately characterise PV modules. The results are useful for developing end-of-life procedures, which is a positive step towards avoiding an e-waste problem and continuing trends of increasing installation and cost reduction in the PV market.

The Regulatory Challenges of Decommissioning Nuclear Power Plants in Korea - 13101

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

Lee, Jungjoon; Ahn, Sangmyeon; Choi, Kyungwoo

As of 2012, 23 units of nuclear power plants are in operation, but there is no experience of permanent shutdown and decommissioning of nuclear power plant in Korea. It is realized that, since late 1990's, improvement of the regulatory framework for decommissioning has been emphasized constantly from the point of view of International Atomic Energy Agency (IAEA)'s safety standards. And it is known that now IAEA prepare the safety requirement on decommissioning of facilities, its title is the Safe Decommissioning of Facilities, General Safety Requirement Part 6. According to the result of IAEA's Integrated Regulatory Review Service (IRRS) mission tomore » Korea in 2011, it was recommended that the regulatory framework for decommissioning should require decommissioning plans for nuclear installations to be constructed and operated and these plans should be updated periodically. In addition, after the Fukushima nuclear disaster in Japan in March of 2011, preparedness for early decommissioning caused by an unexpected severe accident became also important issues and concerns. In this respect, it is acknowledged that the regulatory framework for decommissioning of nuclear facilities in Korea need to be improved. First of all, we identify the current status and relevant issues of regulatory framework for decommissioning of nuclear power plants compared to the IAEA's safety standards in order to achieve our goal. And then the plan is to be established for improvement of regulatory framework for decommissioning of nuclear power plants in Korea. After dealing with it, it is expected that the revised regulatory framework for decommissioning could enhance the safety regime on the decommissioning of nuclear power plants in Korea in light of international standards. (authors)« less

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2012-09-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67836; File No. SR-NYSEArca-2012-100] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend NYSE Arca Options Rule 6.96 by Adding a New Paragraph (c) That Addresses the Authority of the Exchange or Archipelago Securities LLC...

77 FR 65030 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68066; File No. SR-NYSEMKT-2012-52] Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Rule 17-- Equities To Add a New Paragraph (c)(3) Addressing the Authority of the Exchange or Archipelago Securities LLC To Cancel Orders...

77 FR 65040 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68067; File No. SR-NYSE-2012-53] Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE Rule 17 To Add a New Paragraph (c)(3) Addressing the Authority of the Exchange or Archipelago Securities LLC To Cancel...

77 FR 70496 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68260; File No. SR-C2-2012-038] Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Proposed Rule Change To Address Authority To Cancel Orders When a Technical or Systems Issue Occurs and To Describe the Operation of Routing Service Error Accounts November 19, 2012....

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

PubMed Central

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

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.

Addressing Uncertainty in the ISCORS Multimedia Radiological Dose Assessment of Municipal Sewage Sludge and Ash

NASA Astrophysics Data System (ADS)

Chiu, W. A.; Bachmaier, J.; Bastian, R.; Hogan, R.; Lenhart, T.; Schmidt, D.; Wolbarst, A.; Wood, R.; Yu, C.

2002-05-01

Managing municipal wastewater at publicly owned treatment works (POTWs) leads to the production of considerable amounts of residual solid material, which is known as sewage sludge or biosolids. If the wastewater entering a POTW contains radioactive material, then the treatment process may concentrate radionuclides in the sludge, leading to possible exposure of the general public or the POTW workers. The Sewage Sludge Subcommittee of the Interagency Steering Committee on Radiation Standards (ISCORS), which consists of representatives from the Environmental Protection Agency, the Nuclear Regulatory Commission, the Department of Energy, and several other federal, state, and local agencies, is developing guidance for POTWs on the management of sewage sludge that may contain radioactive materials. As part of this effort, they are conducting an assessment of potential radiation exposures using the Department of Energy's RESidual RADioactivity (RESRAD) family of computer codes developed by Argonne National Laboratory. This poster describes several approaches used by the Subcommittee to address the uncertainties associated with their assessment. For instance, uncertainties in the source term are addressed through a combination of analytic and deterministic computer code calculations. Uncertainties in the exposure pathways are addressed through the specification of a number of hypothetical scenarios, some of which can be scaled to address changes in exposure parameters. In addition, the uncertainty in some physical and behavioral parameters are addressed through probabilistic methods.

Regulatory mechanisms link phenotypic plasticity to evolvability

PubMed Central

van Gestel, Jordi; Weissing, Franz J.

2016-01-01

Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question – the optimal timing of bacterial sporulation – we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations. PMID:27087393

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.

78 FR 12405 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the... Approval of Change in Ownership, Control, or Business Operations) to provide for a refund of the...

[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.

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…

ApoHRP-based assay to measure intracellular regulatory heme.

PubMed

Atamna, Hani; Brahmbhatt, Marmik; Atamna, Wafa; Shanower, Gregory A; Dhahbi, Joseph M

2015-02-01

The majority of the heme-binding proteins possess a "heme-pocket" that stably binds to heme. Usually known as housekeeping heme-proteins, they participate in a variety of metabolic reactions (e.g., catalase). Heme also binds with lower affinity to the "Heme-Regulatory Motifs" (HRM) in specific regulatory proteins. This type of heme binding is known as exchangeable or regulatory heme (RH). Heme binding to HRM proteins regulates their function (e.g., Bach1). Although there are well-established methods for assaying total cellular heme (e.g., heme-proteins plus RH), currently there is no method available for measuring RH independent of the total heme (TH). The current study describes and validates a new method to measure intracellular RH. This method is based on the reconstitution of apo-horseradish peroxidase (apoHRP) with heme to form holoHRP. The resulting holoHRP activity is then measured with a colorimetric substrate. The results show that apoHRP specifically binds RH but not with heme from housekeeping heme-proteins. The RH assay detects intracellular RH. Furthermore, using conditions that create positive (hemin) or negative (N-methyl protoporphyrin IX) controls for heme in normal human fibroblasts (IMR90), the RH assay shows that RH is dynamic and independent of TH. We also demonstrated that short-term exposure to subcytotoxic concentrations of lead (Pb), mercury (Hg), or amyloid-β (Aβ) significantly alters intracellular RH with little effect on TH. In conclusion the RH assay is an effective assay to investigate intracellular RH concentration and demonstrates that RH represents ∼6% of total heme in IMR90 cells.

Risk Perceptions of Little Cigar and Cigarillo Smoking Among Adult Current Cigarette Smokers.

PubMed

Sterling, Kymberle L; Majeed, Ban A; Nyman, Amy; Eriksen, Michael

2017-11-01

Few studies have examined the perceptions of risk of little cigar and cigarillo (LCC) smoking among cigarette smokers, which is important for expanding regulatory policies and developing prevention programs. We examined current cigarette smokers' perceived harm of LCC smoking, and determined whether these perceptions were associated with susceptibility and intention to continue smoking LCCs. Data were from the 2014 Tobacco Products and Risk Perceptions Survey of a probability sample of 5717 US adults. Data were analyzed for a subsample of 1191 current cigarette smokers who were stratified into three groups: (1) dual current cigarette smokers who had ever used LCCs, (2) current smokers susceptible to LCC smoking, and (3) current smokers who were not susceptible to LCC smoking. Overall, 47.2% of participants were dual smokers, 12.7% were susceptible to LCC smoking, and 40.1% were not susceptible. Perceptions of risk of LCCs varied across the groups. Dual smokers were more likely to perceive that daily LCC smoking is "very risky" (OR = 1.64, 95% CI = 1.08, 2.41) while occasional LCC smoking is only "somewhat risky" (OR = 1.71, 95% CI = 1.02, 2.87). Of the dual smokers, 20.7% intended to continue smoking LCCs in the future. Perceptions of addiction and risk of daily LCC smoking significantly predicted intention to continue LCC smoking. Addiction perceptions also significantly predicted susceptibility to initiate LCC smoking. Perceptions about harms from and addiction to LCCs could predict future LCC smoking. Health communication campaigns need to address the harms of LCCs. Our data suggest that perceptions of risk about the addictiveness of LCCs and frequency of use are important determinants of the LCC smoking susceptibility among some cigarette smokers and intended continued use among cigarette smokers with a history of LCC use. Health communication campaigns should address misperceptions related to LCCs. © The Author 2016. Published by Oxford University Press on

75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62476; File No. SR-FINRA-2010-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule Change To Amend FINRA Rule 8312 (FINRA BrokerCheck Disclosure) July 8, 2010. I. Introduction On March 30, 2010, the Financial Industry Regulatory...

Strategy in Regulatory Decision-Making for Management of Progressive Multifocal Leukoencephalopathy.

PubMed

Segec, A; Keller-Stanislawski, B; Vermeer, N S; Macchiarulo, C; Straus, S M; Hidalgo-Simon, A; De Bruin, M L

2015-11-01

Progressive multifocal leukoencephalopathy (PML) has been observed after the use of several medicines, including monoclonal antibodies. As these drugs play important roles in the therapeutic armamentarium, it is important to address the challenges that this severe adverse reaction poses to the safe use of medicines. Considering the need for consistent outcomes of regulatory decisions, the European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) used PML as an example to develop a systematic approach to labeling and risk minimization. © 2015 American Society for Clinical Pharmacology and Therapeutics.

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...

Climate Change Education: Preparing Future and Current Business Leaders--A Workshop Summary

ERIC Educational Resources Information Center

Storksdieck, Martin

2014-01-01

Climate change poses challenges as well as opportunities for businesses and, broadly speaking for the entire economy. Businesses will be challenged to provide services or products with less harmful influence on the climate; respond to a changing policy, regulatory, and market environment; and provide new services and products to help address the…

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

PubMed

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

2015-03-31

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

Stress spillover in early marriage: the role of self-regulatory depletion.

PubMed

Buck, April A; Neff, Lisa A

2012-10-01

Stressful experiences external to a marriage (e.g., work stress, finances) are often associated with poor relationship functioning and lowered marital satisfaction, a phenomenon called stress spillover. To date, however, little attention has been devoted to understanding the specific mechanisms through which stress may lead to maladaptive relationship patterns. Drawing from theories of self-regulatory depletion, it was predicted that coping with external stress is an effortful process that consumes spouses' regulatory resources, leaving spouses with less energy to effectively respond to their relationship issues. The current study relied on a sample of newly married couples to examine whether self-regulatory depletion may account for the link between external stress and relationship well-being. Couples were asked to complete a 14-day daily diary that assessed their daily stress, their state of self-regulatory depletion, their marital behaviors, and their daily marital appraisals. Within-person analyses revealed that, on average, couples experienced stress spillover, such that on days when their stress was higher than usual they reported enacting more negative behaviors toward their partner and endorsed less positive appraisals of the relationship. Further analyses confirmed that self-regulatory depletion accounted for a majority of these spillover effects. These findings suggest that even happy couples may find it difficult to engage in adaptive relationship processes under conditions of stress. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Regulatory Considerations in the Design and Manufacturing of Implantable 3D‐Printed Medical Devices

PubMed Central

Morrison, Robert J.; Kashlan, Khaled N.; Flanangan, Colleen L.; Wright, Jeanne K.; Green, Glenn E.; Hollister, Scott J.

2015-01-01

Abstract Three‐dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D‐printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D‐printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Postprinting considerations unique to 3D‐printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group's 3D‐printed bioresorbable implantable device. PMID:26243449

The Environmental Protection Agency in the Early Trump Administration: Prelude to Regulatory Capture.

PubMed

Dillon, Lindsey; Sellers, Christopher; Underhill, Vivian; Shapiro, Nicholas; Ohayon, Jennifer Liss; Sullivan, Marianne; Brown, Phil; Harrison, Jill; Wylie, Sara

2018-04-01

We explore and contextualize changes at the Environmental Protection Agency (EPA) over the first 6 months of the Trump administration, arguing that its pro-business direction is enabling a form of regulatory capture. We draw on news articles, public documents, and a rapid response, multisited interview study of current and retired EPA employees to (1) document changes associated with the new administration, (2) contextualize and compare the current pro-business makeover with previous ones, and (3) publicly convey findings in a timely manner. The lengthy, combined experience of interviewees with previous Republican and Democratic administrations made them valuable analysts for assessing recent shifts at the Scott Pruitt-led EPA and the extent to which these shifts steer the EPA away from its stated mission to "protect human and environmental health." Considering the extent of its pro-business leanings in the absence of mitigating power from the legislative branch, we conclude that its regulatory capture has become likely-more so than at similar moments in the agency's 47-year history. The public and environmental health consequences of regulatory capture of the EPA will probably be severe and far-reaching.

The Environmental Protection Agency in the Early Trump Administration: Prelude to Regulatory Capture

PubMed Central

Sellers, Christopher; Underhill, Vivian; Shapiro, Nicholas; Ohayon, Jennifer Liss; Sullivan, Marianne; Brown, Phil; Harrison, Jill; Wylie, Sara

2018-01-01

We explore and contextualize changes at the Environmental Protection Agency (EPA) over the first 6 months of the Trump administration, arguing that its pro-business direction is enabling a form of regulatory capture. We draw on news articles, public documents, and a rapid response, multisited interview study of current and retired EPA employees to (1) document changes associated with the new administration, (2) contextualize and compare the current pro-business makeover with previous ones, and (3) publicly convey findings in a timely manner. The lengthy, combined experience of interviewees with previous Republican and Democratic administrations made them valuable analysts for assessing recent shifts at the Scott Pruitt–led EPA and the extent to which these shifts steer the EPA away from its stated mission to “protect human and environmental health.” Considering the extent of its pro-business leanings in the absence of mitigating power from the legislative branch, we conclude that its regulatory capture has become likely—more so than at similar moments in the agency’s 47-year history. The public and environmental health consequences of regulatory capture of the EPA will probably be severe and far-reaching. PMID:29698086

Using FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) to isolate active regulatory DNA

PubMed Central

Simon, Jeremy M.; Giresi, Paul G.; Davis, Ian J.; Lieb, Jason D.

2013-01-01

Eviction or destabilization of nucleosomes from chromatin is a hallmark of functional regulatory elements of the eukaryotic genome. Historically identified by nuclease hypersensitivity, these regulatory elements are typically bound by transcription factors or other regulatory proteins. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) is an alternative approach to identify these genomic regions and has proven successful in a multitude of eukaryotic cell and tissue types. Cells or dissociated tissues are crosslinked briefly with formaldehyde, lysed, and sonicated. Sheared chromatin is subjected to phenol-chloroform extraction and the isolated DNA, typically encompassing 1–3% of the human genome, is purified. We provide guidelines for quantitative analysis by PCR, microarrays, or next-generation sequencing. Regulatory elements enriched by FAIRE display high concordance with those identified by nuclease hypersensitivity or ChIP, and the entire procedure can be completed in three days. FAIRE exhibits low technical variability, which allows its use in large-scale studies of chromatin from normal or diseased tissues. PMID:22262007

Legislative and Regulatory Actions Needed to Deal with a Changing Domestic Telecommunications Industry.

DTIC Science & Technology

1981-09-24

procedures? GAO recommends that the Congress address these questions by amending the Communications Act of 1934 to establish the basic framework to create...concerns with rate of return/rate base regulation 198 VII Basic procedures used in establishing rates of return 201 VIII Problems regarding AT&T’s rate...prompted a critical reexamination of the basic communications policy and regulatory methods con- tained in the Communications Act of 1934 (47 U.S.C

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.

Department of Defense Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... Register is mandated for the regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U... the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because... Flexibility Act. Printing of these entries is limited to fields that contain information required by the...

An Investigation of Organizational and Regulatory Discourses of Workplace Bullying.

PubMed

Johnson, Susan L; Boutain, Doris M; Tsai, Jenny H-C; de Castro, Arnold B

2015-10-01

Organizations use policies to set standards for employee behaviors. Although many organizations have policies that address workplace bullying, previous studies have found that these policies affect neither workplace bullying for targets who are seeking assistance in ending the behaviors nor managers who must address incidents of bullying. This article presents the findings of a study that used critical discourse analysis to examine the language used in policies written by health care organizations and regulatory agencies to regulate workplace bullying. The findings suggest that the discussion of workplace bullying overlaps with discussions of disruptive behaviors and harassment. This lack of conceptual clarity can create difficulty for managers in identifying, naming, and disciplining incidents of workplace bullying. The documents also primarily discussed workplace bullying as a patient safety concern. This language is in conflict with organizations attending to worker well-being with regard to workplace bullying. © 2015 The Author(s).

An Investigation of Organizational and Regulatory Discourses of Workplace Bullying

PubMed Central

Johnson, Susan L.; Boutain, Doris M.; Tsai, Jenny H.-C.; de Castro, Arnold B.

2017-01-01

Organizations use policies to set standards for employee behaviors. Although many organizations have policies that address workplace bullying, previous studies have found that these policies affect neither workplace bullying for targets who are seeking assistance in ending the behaviors nor managers who must address incidents of bullying. This article presents the findings of a study that used critical discourse analysis to examine the language used in policies written by health care organizations and regulatory agencies to regulate workplace bullying. The findings suggest that the discussion of workplace bullying overlaps with discussions of disruptive behaviors and harassment. This lack of conceptual clarity can create difficulty for managers in identifying, naming, and disciplining incidents of workplace bullying. The documents also primarily discussed workplace bullying as a patient safety concern. This language is in conflict with organizations attending to worker well-being with regard to workplace bullying. PMID:26223898

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

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

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

The critically endangered forest owlet Heteroglaux blewitti is nested within the currently recognized Athene clade: A century-old debate addressed.

PubMed

Koparde, Pankaj; Mehta, Prachi; Reddy, Sushma; Ramakrishnan, Uma; Mukherjee, Shomita; Robin, V V

2018-01-01

Range-restricted species generally have specific niche requirements and may often have unique evolutionary histories. Unfortunately, many of these species severely lack basic research, resulting in poor conservation strategies. The phylogenetic relationship of the Critically Endangered Forest Owlet Heteroglaux blewitti has been the subject of a century-old debate. The current classifications based on non-phylogenetic comparisons of morphology place the small owls of Asia into three genera, namely, Athene, Glaucidium, and Heteroglaux. Based on morphological and anatomical data, H. blewitti has been alternatively hypothesized to belong within Athene, Glaucidium, or its own monotypic genus Heteroglaux. To test these competing hypotheses, we sequenced six loci (~4300 bp data) and performed phylogenetic analyses of owlets. Mitochondrial and nuclear trees were not congruent in their placement of H. blewitti. However, both mitochondrial and nuclear combined datasets showed strong statistical support with high maximum likelihood bootstrap (>/ = 90) and Bayesian posterior probability values (>/ = 0.98) for H. blewitti being nested in the currently recognized Athene group, but not sister to Indian A. brama. The divergence of H. blewitti from its sister taxa was between 4.3 and 5.7 Ma coinciding with a period of drastic climatic changes in the Indian subcontinent. This study presented the first genetic analysis of H. blewitti, a Critically Endangered species, and addressed the long debate on the relationships of the Athene-Heteroglaux-Glaucidium complex. We recommend further studies with more data and complete taxon sampling to understand the biogeography of Indian Athene species.

The critically endangered forest owlet Heteroglaux blewitti is nested within the currently recognized Athene clade: A century-old debate addressed

PubMed Central

Mehta, Prachi; Reddy, Sushma; Ramakrishnan, Uma

2018-01-01

Range-restricted species generally have specific niche requirements and may often have unique evolutionary histories. Unfortunately, many of these species severely lack basic research, resulting in poor conservation strategies. The phylogenetic relationship of the Critically Endangered Forest Owlet Heteroglaux blewitti has been the subject of a century-old debate. The current classifications based on non-phylogenetic comparisons of morphology place the small owls of Asia into three genera, namely, Athene, Glaucidium, and Heteroglaux. Based on morphological and anatomical data, H. blewitti has been alternatively hypothesized to belong within Athene, Glaucidium, or its own monotypic genus Heteroglaux. To test these competing hypotheses, we sequenced six loci (~4300 bp data) and performed phylogenetic analyses of owlets. Mitochondrial and nuclear trees were not congruent in their placement of H. blewitti. However, both mitochondrial and nuclear combined datasets showed strong statistical support with high maximum likelihood bootstrap (>/ = 90) and Bayesian posterior probability values (>/ = 0.98) for H. blewitti being nested in the currently recognized Athene group, but not sister to Indian A. brama. The divergence of H. blewitti from its sister taxa was between 4.3 and 5.7 Ma coinciding with a period of drastic climatic changes in the Indian subcontinent. This study presented the first genetic analysis of H. blewitti, a Critically Endangered species, and addressed the long debate on the relationships of the Athene-Heteroglaux-Glaucidium complex. We recommend further studies with more data and complete taxon sampling to understand the biogeography of Indian Athene species. PMID:29401484

CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data

PubMed Central

O'Connor, Timothy; Bodén, Mikael

2017-01-01

Abstract Identifying the genomic regions and regulatory factors that control the transcription of genes is an important, unsolved problem. The current method of choice predicts transcription factor (TF) binding sites using chromatin immunoprecipitation followed by sequencing (ChIP-seq), and then links the binding sites to putative target genes solely on the basis of the genomic distance between them. Evidence from chromatin conformation capture experiments shows that this approach is inadequate due to long-distance regulation via chromatin looping. We present CisMapper, which predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues. Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression. CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF. PMID:28204599

Addressing School Violence in the 21st Century

ERIC Educational Resources Information Center

Angkaw, John P.

2006-01-01

The purpose of this report is to address and review school violence and the implications it has on educators and school systems in today's society. It will lead a discussion on the current state faced by North American educators and school systems and the possible solutions that could be implemented to reduce school violence. This report is…

75 FR 52574 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change To Reinstitute Short Exempt Marking for Trade Reporting and OATS August 20, 2010. Pursuant to... is hereby given that on August 6, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA...

76 FR 60567 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change To Create an Exemption From Certain Reporting Obligations Under the Equity Trade Reporting Rules... September 16, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

75 FR 8169 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change To Amend the Codes of Arbitration Procedure To Provide for Attorney Representation of Non-Party... Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers...

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…

Knowledge sharing to facilitate regulatory decision-making in regard to alternatives to animal testing: Report of an EPAA workshop.

PubMed

Ramirez, Tzutzuy; Beken, Sonja; Chlebus, Magda; Ellis, Graham; Griesinger, Claudius; De Jonghe, Sandra; Manou, Irene; Mehling, Annette; Reisinger, Kerstin; Rossi, Laura H; van Benthem, Jan; van der Laan, Jan Willem; Weissenhorn, Renate; Sauer, Ursula G

2015-10-01

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a workshop Knowledge sharing to facilitate regulatory decision-making. Fifty invited participants from the European Commission, national and European agencies and bodies, different industry sectors (chemicals, cosmetics, fragrances, pharmaceuticals, vaccines), and animal protection organizations attended the workshop. Four case studies exemplarily revealed which procedures are in place to obtain regulatory acceptance of new test methods in different sectors. Breakout groups discussed the status quo identifying the following facilitators for regulatory acceptance of alternatives to animal testing: Networking and communication (including cross-sector collaboration, international cooperation and harmonization); involvement of regulatory agencies from the initial stages of test method development on; certainty on prerequisites for test method acceptance including the establishment of specific criteria for regulatory acceptance. Data sharing and intellectual property issues affect many aspects of test method development, validation and regulatory acceptance. In principle, all activities should address replacement, reduction and refinement methods (albeit animal testing is generally prohibited in the cosmetics sector). Provision of financial resources and education support all activities aiming at facilitating the acceptance and use of alternatives to animal testing. Overall, workshop participants recommended building confidence in new methodologies by applying and gaining experience with them. Copyright © 2015 Elsevier Inc. All rights reserved.

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 ...

Department of Defense Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U.S.C. 602), the Department of Defense's printed agenda entries include only: (1) Rules that are in the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because they are likely to have a significant...

The prospect for international regulatory interventions in embryo transfer and reproductive technologies in the next century.

PubMed

Evans, B R

1999-01-01

Historically, international regulatory interventions in the area of animal reproductive technologies have focused on the need for mitigation against the dissemination of diseases with the movement of genetics and germplasm across international borders. The continued globalization of agriculture under the Sanitary/Phytosanitary (SPS) Agreement of the World Trade Organization (WTO) ensures that disease considerations arising from third and fourth generation reproductive technologies such as in vitro fertilized embryos, transgenics and xenotransplantation will continue to give rise to animal health regulatory measures. Furthermore, in the aftermath of the raising of the public consciousness and the ensuing consumer confidence crisis concerning animal husbandry and livestock production practices following the Bovine Spongiform Encephalopathy outbreak, evolving societal values are expected to expand regulatory considerations to address veterinary public health and ethical concerns. Consequently, it is expected that the role of the International Embryo Transfer Society in fostering meaningful dialogue and profiling of the research necessary to provide for appropriate science based regulation development will increase in importance.

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.

76 FR 62128 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change to Amend Certain Trade Reporting and Compliance Rules September 30, 2011. Pursuant to Section 19(b... hereby given that on September 22, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA...

STS-71 crew addresses news media

NASA Technical Reports Server (NTRS)

1995-01-01

Following their arrival at KSC's Shuttle Landing Facility, the STS-71 flight crew takes a moment to address news media gathered to greet them. The journey from Johnson Space Center in Houston brings the flight crew one step closer to an historic spaceflight, the first docking of the U.S. Space Shuttle with the Russian Space Station Mir. The countdown clock already has begun ticking toward liftoff of the Shuttle Atlantis on that flight, currently scheduled for June 23 at 5:08 p.m. EDT.

A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

PubMed

Abraham, John; Davis, Courtney

2005-09-01

By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

Current and new developments in transport and regulatory issues concerning radioisotopes: managing change for minimum business impact

NASA Astrophysics Data System (ADS)

Bennett, Neil; Coppell, David; Rogers, David; Schrader, John

2004-09-01

Changes in the regulatory framework governing the Radiation Processing Industry have the potential to make a real business impact on day-to-day profitability. Many areas of the Radiation Processing Industry are affected by changes in the regulatory framework within which these areas are managed. When planning for such changes the transportation element in the shipment of sealed cobalt radiation sources is an area that is often neglected by some parts of the distribution chain. A balance must be struck between the cobalt supplier and the facility operator/customer that rests upon how much the customer needs to know about the intricacies of cobalt shipment. The objective of this paper is to highlight areas of possible business impact and reassure the users of sealed radiation sources that the global suppliers of these products are used to negotiating local variations in regulations governing the physical transportation of radiation sources, changes in regulations governing the design, manufacture and use of transportation containers and changes in the availability of commercial shippers and shipping routes. The major suppliers of industrial quantities of cobalt-60 are well placed to lead their customers through this complex process as a matter of routine.

77 FR 19401 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change Amending...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66656; File No. SR-NYSEArca-2012-22] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change Amending NYSE Arca Equities Rule 7.45 Adding a New Paragraph (d) That Addresses the Authority of the Exchange or Archipelago Securities LLC To Cancel Orders When a...

Engineering nucleases for gene targeting: safety and regulatory considerations.

PubMed

Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe

2014-01-25

Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.

Factors influencing physicians' choice of workplace: systematic review of drivers of attrition and policy interventions to address them.

PubMed

El Koussa, Maria; Atun, Rifat; Bowser, Diana; Kruk, Margaret E

2016-12-01

The movement of skilled physicians from the public to the private sector is a key constraint to achieving universal health coverage and is currently affecting health systems worldwide. This systematic review aims to assess factors influencing physicians' choice of workplace, and policy interventions for retaining physicians in the public sector. Five literature databases were searched. Studies were included in the review if they focused on at least one of the following criteria: (i) incentives or motivators for retaining physicians in the public sector, (ii) pull factors that encouraged physicians to move to the private sector, (iii) push factors that forced physicians to leave the public sector, (iv) policy interventions or case studies that addressed physician retention in the public sector, and (v) qualitative reviews of policy interventions that were implemented in different health system settings. Nineteen articles met the inclusion criteria. Six major themes that affected physicians' choice of workplace were identified including: financial incentives, career development, infrastructure and staffing, professional work environment, workload and autonomy. The majority of the studies suggested that the use of financial incentives was a motivator in retaining physicians in the public sector. The review also identified policy interventions including: regulatory controls, incentives and management reforms. Regulatory controls and incentives were the two most frequently reported policy interventions. While factors affecting physicians' choice of workplace are country specific, financial incentives and professional development are core factors. Other factors are highly influenced by context, and thus, it would be useful for future cross-country research to use standardized data collection tools, allowing comparison of contextual factors as well as the examination of how context affects physician retention in the public sector.

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

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

Jennings, S.D.

1990-04-01

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

76 FR 70523 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change to Adopt FINRA Rule 4524 (Supplemental FOCUS Information) and Proposed Supplementary Schedule to...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the...

Professional and Regulatory Search

EPA Pesticide Factsheets

Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

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

RSAT: regulatory sequence analysis tools.

PubMed

Thomas-Chollier, Morgane; Sand, Olivier; Turatsinze, Jean-Valéry; Janky, Rekin's; Defrance, Matthieu; Vervisch, Eric; Brohée, Sylvain; van Helden, Jacques

2008-07-01

The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning and feature map drawing. Random controls can be performed with random gene selections or by generating random sequences according to a variety of background models (Bernoulli, Markov). Beyond the original word-based pattern-discovery tools (oligo-analysis and dyad-analysis), we recently added a battery of tools for matrix-based detection of cis-acting elements, with some original features (adaptive background models, Markov-chain estimation of P-values) that do not exist in other matrix-based scanning tools. The web server offers an intuitive interface, where each program can be accessed either separately or connected to the other tools. In addition, the tools are now available as web services, enabling their integration in programmatic workflows. Genomes are regularly updated from various genome repositories (NCBI and EnsEMBL) and 682 organisms are currently supported. Since 1998, the tools have been used by several hundreds of researchers from all over the world. Several predictions made with RSAT were validated experimentally and published.

ReNE: A Cytoscape Plugin for Regulatory Network Enhancement

PubMed Central

Politano, Gianfranco; Benso, Alfredo; Savino, Alessandro; Di Carlo, Stefano

2014-01-01

One of the biggest challenges in the study of biological regulatory mechanisms is the integration, americanmodeling, and analysis of the complex interactions which take place in biological networks. Despite post transcriptional regulatory elements (i.e., miRNAs) are widely investigated in current research, their usage and visualization in biological networks is very limited. Regulatory networks are commonly limited to gene entities. To integrate networks with post transcriptional regulatory data, researchers are therefore forced to manually resort to specific third party databases. In this context, we introduce ReNE, a Cytoscape 3.x plugin designed to automatically enrich a standard gene-based regulatory network with more detailed transcriptional, post transcriptional, and translational data, resulting in an enhanced network that more precisely models the actual biological regulatory mechanisms. ReNE can automatically import a network layout from the Reactome or KEGG repositories, or work with custom pathways described using a standard OWL/XML data format that the Cytoscape import procedure accepts. Moreover, ReNE allows researchers to merge multiple pathways coming from different sources. The merged network structure is normalized to guarantee a consistent and uniform description of the network nodes and edges and to enrich all integrated data with additional annotations retrieved from genome-wide databases like NCBI, thus producing a pathway fully manageable through the Cytoscape environment. The normalized network is then analyzed to include missing transcription factors, miRNAs, and proteins. The resulting enhanced network is still a fully functional Cytoscape network where each regulatory element (transcription factor, miRNA, gene, protein) and regulatory mechanism (up-regulation/down-regulation) is clearly visually identifiable, thus enabling a better visual understanding of its role and the effect in the network behavior. The enhanced network produced by Re

Automated selection of synthetic biology parts for genetic regulatory networks.

PubMed

Yaman, Fusun; Bhatia, Swapnil; Adler, Aaron; Densmore, Douglas; Beal, Jacob

2012-08-17

Raising the level of abstraction for synthetic biology design requires solving several challenging problems, including mapping abstract designs to DNA sequences. In this paper we present the first formalism and algorithms to address this problem. The key steps of this transformation are feature matching, signal matching, and part matching. Feature matching ensures that the mapping satisfies the regulatory relationships in the abstract design. Signal matching ensures that the expression levels of functional units are compatible. Finally, part matching finds a DNA part sequence that can implement the design. Our software tool MatchMaker implements these three steps.

Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 2. Results

NASA Astrophysics Data System (ADS)

Massmann, Joel; Freeze, R. Allan

1987-02-01

The risk-cost-benefit analysis developed in the companion paper (J. Massmann and R. A. Freeze, this issue) is here applied to (1) an assessment of the relative worth of containment-construction activities, site-exploration activities, and monitoring activities as components of a design strategy for the owner/operator of a waste management facility; (2) an assessment of alternative policy options available to a regulatory agency; and (3) a case history. Sensitivity analyses designed to address the first issue show that the allocation of resources by the owner/operator is sensitive to the stochastic parameters used to describe the hydraulic conductivity field at a site. For the cases analyzed, the installation of a dense monitoring network is of less value to the owner/operator than a more conservative containment design. Sensitivity analyses designed to address the second issue suggest that from a regulatory perspective, design standards should be more effective than performance standards in reducing risk, and design specifications on the containment structure should be more effective than those on the monitoring network. Performance bonds posted before construction have a greater potential to influence design than prospective penalties to be imposed at the time of failure. Siting on low-conductivity deposits is a more effective method of risk reduction than any form of regulatory influence. Results of the case history indicate that the methodology can be successfully applied at field sites.

Role of sport medicine professionals in addressing psychosocial aspects of sport-injury rehabilitation: professional athletes' views.

PubMed

Arvinen-Barrow, Monna; Massey, William V; Hemmings, Brian

2014-01-01

Research from the sport medicine professional's (SMP's) perspective indicates that SMPs are often required to address psychosocial aspects of injuries during treatment. However, only a few authors have investigated injured athletes' experiences with these concerns. To explore injured professional athletes' views on the role of SMPs in the psychosocial aspects of sport-injury rehabilitation. Design : Qualitative study. Professional association football and rugby union clubs. Ten professional, male football (n = 4; 40%) and rugby union (n = 6; 60%) players (age = 22.4 ± 3.4 years). Data Collection and Analysis : We collected data using a semistructured interview guide, and the data were then transcribed and analyzed following the interpretative phenomenological analysis guidelines. We peer reviewed and triangulated the established emergent themes to establish trustworthiness. Athletes in our study viewed injuries as "part and parcel" of their sports. Despite normalizing sport injuries, athletes reported frequent feelings of frustration and self-doubt throughout the rehabilitation process. However, athletes' perceived the role of SMPs in injury rehabilitation as addressing physical concerns; any intervention aimed at psychosocial outcomes (eg, motivation, confidence) needed to be subtle and indirect. The SMPs working with injured athletes need to understand the psychosocial principles that underpin athletes' sport-injury processes and the effect psychosocial reactions can have on athletes. Moreover, SMPs must understand the self-regulatory processes that may take place throughout injury rehabilitation and be able to apply psychological principles in natural and subtle ways to aid athletes' self-regulatory abilities.

Cleaning up our Federal energy regulatory mess

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

Kennedy, R.T.

1978-08-01

The new Department of Energy is making much effort to cut back on overlaps of regulations in regard to energy. Several governmental agencies were absorbed into DOE, but many of the previous agencies' policies are still on the books. The Energy Reorganization Act of 1977 did not eliminate the problem of regulatory overlap and confusion, the author says. Also, our future national energy policy will have to rest on this very complex of laws and regulations, he says. The author, being a former deputy administrator of the FEA, uses the nuclear industry to discuss ''the confusion.'' He concludes that eachmore » of us ''has a responsibility to clean up the energy regulation situation. Broad national policy issues must be addressed by Congress and the President. The States must focus hard on ways to simplify and strengthen their processes; and Federal agencies must look to ways to improve their interface with the states and to reduce duplication both with the states and with each other. All regulatory agencies must, mindful of their role in the process, police themselves, and keep a close eye on how that process is working. Finally, each government official and citizen must do his part to bring problems and solutions to the attention of the appropriate officials. For you are the watchdogs in this process, the keystone upon which our system rests.'' (MCW)« less

Data monitoring committees: Promoting best practices to address emerging challenges.

PubMed

Fleming, Thomas R; DeMets, David L; Roe, Matthew T; Wittes, Janet; Calis, Karim A; Vora, Amit N; Meisel, Alan; Bain, Raymond P; Konstam, Marvin A; Pencina, Michael J; Gordon, David J; Mahaffey, Kenneth W; Hennekens, Charles H; Neaton, James D; Pearson, Gail D; Andersson, Tomas Lg; Pfeffer, Marc A; Ellenberg, Susan S

2017-04-01

Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees' independence and effectiveness. An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees. Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee's independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and

Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing.

PubMed

Engisch, William; Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing, primarily due to regulatory uncertainty. This paper aims to help address these concerns by introducing methods for batch definition, raw material traceability, and sensor frequency determination. All of the methods are based on established engineering and mathematical principles, especially the residence time distribution (RTD). This paper introduces a risk-based approach to address content uniformity challenges of continuous manufacturing. All of the detailed methods are discussed using a direct compaction manufacturing line as the main example, but the techniques can easily be applied to other continuous manufacturing methods such as wet and dry granulation, hot melt extrusion, capsule filling, etc.

Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

PubMed Central

Murray, Heath; Koh, Alan

2014-01-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes. PMID:25340815

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

PubMed

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

2015-02-01

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

78 FR 17975 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of a Proposed Rule Change Relating to FINRA Rule 8313 (Release of Disciplinary Complaints, Decisions and Other Information... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's...

76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

Dynamical modeling and analysis of large cellular regulatory networks

NASA Astrophysics Data System (ADS)

Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

2013-06-01

The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

Global Governance Mechanisms to Address Antimicrobial Resistance.

PubMed

Padiyara, Ponnu; Inoue, Hajime; Sprenger, Marc

2018-01-01

Since their discovery, antibiotics, and more broadly, antimicrobials, have been a cornerstone of modern medicine. But the overuse and misuse of these drugs have led to rising rates of antimicrobial resistance, which occurs when bacteria adapt in ways that render antibiotics ineffective. A world without effective antibiotics can have drastic impacts on population health, global development, and the global economy. As a global common good, antibiotic effectiveness is vulnerable to the tragedy of the commons, where a shared limited resource is overused by a community when each individual exploits the finite resource for their own benefit. A borderless threat like antimicrobial resistance requires global governance mechanisms to mitigate its emergence and spread, and it is the responsibility of all countries and relevant multilateral organizations. These mechanisms can be in the form of legally binding global governance mechanisms such as treaties and regulatory standards or nonbinding mechanisms such as political declarations, resolutions, or guidelines. In this article, we argue that while both are effective methods, the strong, swift, and coordinated action needed to address rising rates of antimicrobial resistance will be better served through legally binding governance mechanisms.

The European Safeguards Research and Development Association Addresses Safeguards and Nonproliferation

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

Janssens-Maenhout, Greet; Kusumi, R.; Daures, Pascal A.

2010-06-16

a broad range of subjects, including nuclear material accountancy principles, legal definitions and the regulatory base and inspection tools and techniques. This 60% core part is given by representatives from regulatory bodies (The International Atomic Energy Agency (IAEA), Institute for Radiological Protection and Nuclear Safety, Directorate General for Nuclear Energy and Transport), industry (AREVA, British Nuclear Group), and research (Stockholm University, Hamburg University, Joint Research Centre-Institute of Transuranic Elements, and Joint Research Centre-Institute for the Protection of the Citizen). The remaining part is completed with topical lectures addressed by invited lecturers, such as from Pacific Northwest National Laboratory and the IAEA addressing topics of physical protection, illicit trafficking, the Iraq case study, exercises, including satellite imagery interpretation etc. With this structure of a stable core plus a variable set of invited lectures, the course will remain sustainable and up-to-date. A syllabus provides the students a homogeneous set of information material in nuclear safeguards and nonproliferation matters at the European and international level. In this way, the ESARDA TKMWG aims to contribute to a two-fold scientific-technical and political-juridical education and training.« less

Department of Transportation Agency Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] [Department of Transportation Agency Semiannual Regulatory Agenda ] Part XIII Department of Transportation Semiannual Regulatory Agenda [[Page 79812

The GÉANT network: addressing current and future needs of the HEP community

NASA Astrophysics Data System (ADS)

Capone, Vincenzo; Usman, Mian

2015-12-01

The GÉANT infrastructure is the backbone that serves the scientific communities in Europe for their data movement needs and their access to international research and education networks. Using the extensive fibre footprint and infrastructure in Europe the GÉANT network delivers a portfolio of services aimed to best fit the specific needs of the users, including Authentication and Authorization Infrastructure, end-to-end performance monitoring, advanced network services (dynamic circuits, L2-L3VPN, MD-VPN). This talk will outline the factors that help the GÉANT network to respond to the needs of the High Energy Physics community, both in Europe and worldwide. The Pan-European network provides the connectivity between 40 European national research and education networks. In addition, GÉANT also connects the European NRENs to the R&E networks in other world region and has reach to over 110 NREN worldwide, making GÉANT the best connected Research and Education network, with its multiple intercontinental links to different continents e.g. North and South America, Africa and Asia-Pacific. The High Energy Physics computational needs have always had (and will keep having) a leading role among the scientific user groups of the GÉANT network: the LHCONE overlay network has been built, in collaboration with the other big world REN, specifically to address the peculiar needs of the LHC data movement. Recently, as a result of a series of coordinated efforts, the LHCONE network has been expanded to the Asia-Pacific area, and is going to include some of the main regional R&E network in the area. The LHC community is not the only one that is actively using a distributed computing model (hence the need for a high-performance network); new communities are arising, as BELLE II. GÉANT is deeply involved also with the BELLE II Experiment, to provide full support to their distributed computing model, along with a perfSONAR-based network monitoring system. GÉANT has also

Department of the Interior Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] [Department of the Interior Semiannual Regulatory Agenda] Part X Department of the Interior Semiannual Regulatory Agenda [[Page 79796

76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance..., and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the... in sections A, B, and C below, of the most significant aspects of such statements. A. Self-Regulatory...

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

Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues.

PubMed

Sanders, M E; Huis in't Veld, J

1999-01-01

Properly formulated probiotic-containing foods offer consumers a low risk, low cost dietary component that has the potential to promote health in a variety of ways. Several such products are available commercially, although markets in Japan and Europe are more developed than in the USA. Once healthful attributes of a probiotic product have been identified, there remain microbiological, product, regulatory and labeling issues to be addressed prior to marketing. Microbiological and product issues include safety, effective scale-up for manufacturing, definition of probiotic activity, probiotic stability in the product over the course of product manufacture, shelf-life and consumption, definition of effective dose and target population(s), and development of quality assurance approaches. Examples of probiotic-containing foods are given. Regulatory and labeling issues are complicated because they differ for each country, but are likewise critical because they provide the means for communication of the product benefits to the consumer. The regulatory climate worldwide appears to be one of caution about overstating the benefits of such products but at the same time not preventing corporate commitment to marketing.

[Is it possible to improve the preventive usefulness of workers' health surveillance in the current regulatory framework?

PubMed

Rodríguez Jareño, Mari Cruz; De Montserrat I Nonó, Jaume

In Spain, the limited preventive usefulness of health surveillance is determined by the indiscriminate use of nonspecific "generic" health examinations aimed at producing a "fitness for work list", presumably allowing companies to comply with health and safety regulations. This study aimed to produce a technical interpretation of the Spanish Prevention of Risks at Work Act and propose a new conceptual framework to favour greater preventive usefulness of health surveillance within the current regulatory framework. Using qualitative techniques of content analysis, the text of the Law was studied, the key concepts that impeded the fulfilment of the preventive objectives of health surveillance were identified, and a technical interpretation adjusted to regulations was made in order to propose a new conceptual framework RESULTS: This conceptual framework would include: clearly differentiating health surveillance from health examinations (one of its instruments) and from fitness for work evaluations (an independent concept in itself); restricting mandatory health surveillance to situations in which it is "imperative" to carry it out because of the existence of a substantial risk to workers or third parties, including potentially vulnerable workers; and communicating the results of health surveillance through preventive recommendations to the company, reserving fitness for duty certificates -always based on clear, pre-established and justified criteria in relation to risk- for mandatory surveillance. The proposed new conceptual framework falls within the scope of the Spanish Prevention of Risks at Work Act, and its implementation could contribute to improving the preventive usefulness of health surveillance without the need to reform the legislation. Copyright belongs to the Societat Catalana de Salut Laboral.

Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

PubMed Central

Michailidis, George

2014-01-01

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g., wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network. PMID:24586224

Regulatory T cells in cattle and their potential role in bovine paratuberculosis.

PubMed

Coussens, Paul M; Sipkovsky, Sue; Murphy, Brooke; Roussey, Jon; Colvin, Christopher J

2012-05-01

The intracellular bacterium Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease in wild and domestic ruminants. Johne's disease presents as a chronic enteritis with severe inflammation of intestinal tissues, characterized by widespread infiltration of macrophages, the target cell of MAP. Clinical signs of Johne's disease are typically accompanied by a loss of peripheral CD4+ T cell responses to MAP antigens and an increase in anti-MAP serum IgG levels. Recently, it was proposed that regulatory T cells might develop over the lengthy course of subclinical MAP infection. In the past five years, significant progress in defining bovine regulatory T cells has been made. These studies grew out of observations that IL-10 is produced by PBMCs in response to MAP antigen stimulation and that neutralization of this IL-10 could enhance IFN-γ production from MAP-antigen reactive effector T cells. Depletion studies revealed that MAP responsive cell populations producing IL-10 were largely CD4+ and CD25+, although monocytes have also been shown to produce IL-10 in response to MAP. In addition, evidence for a regulatory population of γδ T cells has also begun to accumulate. We summarize current thinking regarding regulatory T cells in MAP infection and provide data suggesting a potential link between regulatory T cells, bovine leukemia virus, and MAP. Copyright © 2012 Elsevier Ltd. All rights reserved.

Application of in vitro neurotoxicity testing for regulatory purposes: Symposium III summary and research needs.

PubMed

Bal-Price, Anna K; Suñol, Cristina; Weiss, Dieter G; van Vliet, Erwin; Westerink, Remco H S; Costa, Lucio G

2008-05-01

Prediction of neurotoxic effects is a key feature in the toxicological profile of many compounds and therefore is required by regulatory testing schemes. Nowadays neurotoxicity assessment required by the OECD and EC test guidelines is based solely on in vivo testing, evaluating mainly effects on neurobehavior and neuropathology, which is expensive, time consuming and unsuitable for screening large number of chemicals. Additionally, such in vivo tests are not always sensitive enough to predict human neurotoxicity and often do not provide information that facilitates regulatory decision-making processes. Incorporation of alternative tests (in vitro testing, computational modelling, QSARs, grouping, read-across, etc.) in screening strategies would speed up the rate at which compound knowledge and mechanistic data are available and the information obtained could be used in the refinement of future in vivo studies to facilitate predictions of neurotoxicity. On 1st June 2007, the European Commission legislation concerning registration, evaluation and authorisation of chemicals (REACH) has entered into force. REACH addresses one of the key issues for chemicals in Europe, the lack of publicly available safety data sheets. It outlines a plan to test approximately 30,000 existing substances. These chemicals are currently produced in volumes greater than 1ton/year and the essential data on the human health and ecotoxicological effects are lacking. It is estimated that approximately 3.9 million test animals (including 2.6 million vertebrates) (Hartung T, Bremer S, Casati S, Coecke S, Corvi R, Fortnaer S, et al. ECVAM's response to the changing political environment for alternatives: consequences of the European Union chemicals and cosmetics policies. ATLA 2003;31:473-81) would be necessary to fulfill the requirements of REACH if the development and establishment of alternative methods is not accepted by regulatory authorities. In an effort to reduce animal use and testing

Addressing Externalities From Swine Production to Reduce Public Health and Environmental Impacts

PubMed Central

Osterberg, David; Wallinga, David

2004-01-01

Animal agriculture in the United States for the most part has industrialized, with negative consequences for air and water quality and antibiotic use. We consider health and environmental impacts of current US swine production and give an overview of current federal, state, and local strategies being used to address them. PMID:15451736

Whip Rule Breaches in a Major Australian Racing Jurisdiction: Welfare and Regulatory Implications

PubMed Central

Hood, Jennifer; McDonald, Carolyn; Wilson, Bethany; McManus, Phil; McGreevy, Paul

2017-01-01

Simple Summary An evidence-based analysis of whip rule breaches in horse racing is needed to address community expectations that racehorses are treated humanely. The study provides the first peer-reviewed characterisation of whip rule breaches and their regulatory outcomes in horseracing, and considers the relationship between rules affecting racing integrity and the welfare of racehorses in a major Australian racing jurisdiction. Abstract Whip use in horseracing is increasingly being questioned on ethical, animal welfare, social sustainability, and legal grounds. Despite this, there is weak evidence for whip use and its regulation by Stewards in Australia. To help address this, we characterised whip rule breaches recorded by Stewards using Stewards Reports and Race Diaries from 2013 and 2016 in New South Wales (NSW) and the Australian Capital Territory (ACT). There were more recorded breaches at Metropolitan (M) than Country (C) or Provincial (P) locations, and by riders of horses that finished first, second, or third than by riders of horses that finished in other positions. The most commonly recorded breaches were forehand whip use on more than five occasions before the 100-metre (m) mark (44%), and whip use that raises the jockey’s arm above shoulder height (24%). It is recommended that racing compliance data be analysed annually to inform the evidence-base for policy, education, and regulatory change, and ensure the welfare of racehorses and racing integrity. PMID:28275207

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.

Global Summit on Regulatory Science 2013.

PubMed

Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

2014-12-01

Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed. Published by Elsevier Inc.

Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades

NASA Astrophysics Data System (ADS)

Hansen, Sabine; Krishna, Sandeep; Semsey, Szabolcs; Lo Svenningsen, Sine

2015-07-01

Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution.

Can Innovation Save Gifted Education? 2010 NAGC Presidential Address

ERIC Educational Resources Information Center

Robinson, Ann

2012-01-01

Connecting innovation with gifted education is a necessity not only in the current political climate but also because it is a field with deeply held beliefs about the importance of problem solving, creativity, imagination, and invention--all critical components of innovation. In this address, the author focuses on three key ideas. First, she…

Interventions addressing general parenting to prevent or treat childhood obesity.

PubMed

Gerards, Sanne M P L; Sleddens, Ester F C; Dagnelie, Pieter C; de Vries, Nanne K; Kremers, Stef P J

2011-06-01

Observational studies increasingly emphasize the impact of general parenting on the development of childhood overweight and obesity. The aim of the current literature review was to provide an overview of interventions addressing general parenting in order to prevent or treat childhood obesity. Electronic literature databases were systematically searched for relevant studies. Seven studies were eligible for inclusion. The studies described four different general parenting programs, which were supplemented with lifestyle components (i.e., physical activity and nutrition). All studies showed significant small to moderate intervention effects on at least one weight-related outcome measure. The current review shows that despite the emerging observational evidence for the role of parenting in children's weight-related outcomes, few interventions have been developed that address general parenting in the prevention of childhood obesity. These interventions provide evidence that the promotion of authoritative parenting is an effective strategy for the prevention and management of childhood obesity.

An Official American Thoracic Society Research Statement: Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling.

PubMed

Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri, Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B

2017-01-15

Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and development of therapeutics targeting AR and to propose approaches and solutions to these specific problems. This Statement is not intended to provide clinical practice recommendations on any disease in which AR is observed and/or plays a role. An international multidisciplinary group from within academia, industry, and the National Institutes of Health, with expertise in multimodal approaches to the study of airway structure and function, pulmonary research and clinical practice in obstructive lung disease, and drug discovery platforms was invited to participate in one internet-based and one face-to-face meeting to address the above-stated goals. Although the majority of the analysis related to AR was in asthma, AR in other diseases was also discussed and considered in the recommendations. A literature search of PubMed was performed to support conclusions. The search was not a systematic review of the evidence. Multiple conceptual, logistical, economic, and regulatory deterrents were identified that limit the performance of AR research and impede accelerated, intensive development of AR-focused therapeutics. Complementary solutions that leverage expertise of academia and industry were proposed to address them. To date, numerous factors related to the intrinsic difficulty in performing AR research, and economic forces that are disincentives for the pursuit of AR treatments, have thwarted the ability to understand AR pathology and mechanisms and to address it clinically. This ATS Research Statement identifies potential solutions for each of these factors and emphasizes the importance of educating the global research community as to the

Evolution of UCP1 Transcriptional Regulatory Elements Across the Mammalian Phylogeny

PubMed Central

Gaudry, Michael J.; Campbell, Kevin L.

2017-01-01

Uncoupling protein 1 (UCP1) permits non-shivering thermogenesis (NST) when highly expressed in brown adipose tissue (BAT) mitochondria. Exclusive to placental mammals, BAT has commonly been regarded to be advantageous for thermoregulation in hibernators, small-bodied species, and the neonates of larger species. While numerous regulatory control motifs associated with UCP1 transcription have been proposed for murid rodents, it remains unclear whether these are conserved across the eutherian mammal phylogeny and hence essential for UCP1 expression. To address this shortcoming, we conducted a broad comparative survey of putative UCP1 transcriptional regulatory elements in 139 mammals (135 eutherians). We find no evidence for presence of a UCP1 enhancer in monotremes and marsupials, supporting the hypothesis that this control region evolved in a stem eutherian ancestor. We additionally reveal that several putative promoter elements (e.g., CRE-4, CCAAT) identified in murid rodents are not conserved among BAT-expressing eutherians, and together with the putative regulatory region (PRR) and CpG island do not appear to be crucial for UCP1 expression. The specificity and importance of the upTRE, dnTRE, URE1, CRE-2, RARE-2, NBRE, BRE-1, and BRE-2 enhancer elements first described from rats and mice are moreover uncertain as these motifs differ substantially—but generally remain highly conserved—in other BAT-expressing eutherians. Other UCP1 enhancer motifs (CRE-3, PPRE, and RARE-3) as well as the TATA box are also highly conserved in nearly all eutherian lineages with an intact UCP1. While these transcriptional regulatory motifs are generally also maintained in species where this gene is pseudogenized, the loss or degeneration of key basal promoter (e.g., TATA box) and enhancer elements in other UCP1-lacking lineages make it unlikely that the enhancer region is pleiotropic (i.e., co-regulates additional genes). Importantly, differential losses of (or mutations within

Development and use of microbial-based cleaning products (MBCPs): Current issues and knowledge gaps.

PubMed

Arvanitakis, George; Temmerman, Robin; Spök, Armin

2018-06-01

Cleaning products containing microbes as active ingredients are becoming increasingly prevalent as an alternative to chemical-based cleaning products. These microbial-based cleaning products (MBCPs) are being used in domestic and commercial settings (i.e., households and businesses) and institutional settings (e.g., hospitals, schools, etc.), in a variety of cleaning activities (hard surface cleaning, odour control, degreasing, septic tank treatments, etc.). They are typically described as "environmentally friendly" and "non-toxic". Publicly available information sources (scientific literature, patent databases, commercial websites) were searched for information on microbial species contained in MBCPs, their mode of action, cleaning applications in which they are used, and their potential impacts on human health and the environment. Although information was found providing a broad indication of microbial genera/species used, information on specific species/strains and quantities produced and sold is generally lacking. This makes it difficult to conduct a meaningful examination of any risks to human health and the environment from the production and use of MBCPs and to determine how effective current policies and regulatory frameworks are in addressing these issues. These and other challenges were addressed at an international workshop in Ottawa, Canada in June 2013 by a number of stakeholders, including industry, government, academic and non-governmental organizations. Copyright © 2017. Published by Elsevier Ltd.

The regulatory framework for safe decommissioning of nuclear power plants in Korea

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

Sangmyeon Ahn; Jungjoon Lee; Chanwoo Jeong

We are having 23 units of nuclear power plants in operation and 5 units of nuclear power plants under construction in Korea as of September 2012. However, we don't have any experience on shutdown permanently and decommissioning of nuclear power plants. There are only two research reactors being decommissioned since 1997. It is realized that improvement of the regulatory framework for decommissioning of nuclear facilities has been emphasized constantly from the point of view of IAEA's safety standards. It is also known that IAEA will prepare the safety requirement on decommissioning of facilities; its title is the Safe Decommissioning ofmore » Facilities, General Safety Requirement Part 6. According to the result of IAEA's Integrated Regulatory Review Service (IRRS) mission to Korea in 2011, it was recommended that the regulatory framework should require decommissioning plans for nuclear installations to be constructed and operated and these plans should be updated periodically. In addition, after the Fukushima nuclear disaster in Japan in March of 2011, preparedness for early decommissioning caused by an unexpected severe accident became important issues and concerns. In this respect, it is acknowledged that the regulatory framework for decommissioning of nuclear facilities in Korea need to be improved. First of all, we focus on identifying the current status and relevant issues of regulatory framework for decommissioning of nuclear power plants compared to the IAEA's safety standards in order to achieve our goal. And then the plan is established for improvement of regulatory framework for decommissioning of nuclear power plants in Korea. It is expected that if the things will go forward as planned, the revised regulatory framework for decommissioning could enhance the safety regime on the decommissioning of nuclear power plants in Korea in light of international standards. (authors)« less

A cis-regulatory logic simulator.

PubMed

Zeigler, Robert D; Gertz, Jason; Cohen, Barak A

2007-07-27

A major goal of computational studies of gene regulation is to accurately predict the expression of genes based on the cis-regulatory content of their promoters. The development of computational methods to decode the interactions among cis-regulatory elements has been slow, in part, because it is difficult to know, without extensive experimental validation, whether a particular method identifies the correct cis-regulatory interactions that underlie a given set of expression data. There is an urgent need for test expression data in which the interactions among cis-regulatory sites that produce the data are known. The ability to rapidly generate such data sets would facilitate the development and comparison of computational methods that predict gene expression patterns from promoter sequence. We developed a gene expression simulator which generates expression data using user-defined interactions between cis-regulatory sites. The simulator can incorporate additive, cooperative, competitive, and synergistic interactions between regulatory elements. Constraints on the spacing, distance, and orientation of regulatory elements and their interactions may also be defined and Gaussian noise can be added to the expression values. The simulator allows for a data transformation that simulates the sigmoid shape of expression levels from real promoters. We found good agreement between sets of simulated promoters and predicted regulatory modules from real expression data. We present several data sets that may be useful for testing new methodologies for predicting gene expression from promoter sequence. We developed a flexible gene expression simulator that rapidly generates large numbers of simulated promoters and their corresponding transcriptional output based on specified interactions between cis-regulatory sites. When appropriate rule sets are used, the data generated by our simulator faithfully reproduces experimentally derived data sets. We anticipate that using simulated

Life cycle assessment part 2: current impact assessment practice.

PubMed

Pennington, D W; Potting, J; Finnveden, G; Lindeijer, E; Jolliet, O; Rydberg, T; Rebitzer, G

2004-07-01

Providing our society with goods and services contributes to a wide range of environmental impacts. Waste generation, emissions and the consumption of resources occur at many stages in a product's life cycle-from raw material extraction, energy acquisition, production and manufacturing, use, reuse, recycling, through to ultimate disposal. These all contribute to impacts such as climate change, stratospheric ozone depletion, photooxidant formation (smog), eutrophication, acidification, toxicological stress on human health and ecosystems, the depletion of resources and noise-among others. The need exists to address these product-related contributions more holistically and in an integrated manner, providing complimentary insights to those of regulatory/process-oriented methodologies. A previous article (Part 1, Rebitzer et al., 2004) outlined how to define and model a product's life cycle in current practice, as well as the methods and tools that are available for compiling the associated waste, emissions and resource consumption data into a life cycle inventory. This article highlights how practitioners and researchers from many domains have come together to provide indicators for the different impacts attributable to products in the life cycle impact assessment (LCIA) phase of life cycle assessment (LCA).

Deciphering the transcriptional cis-regulatory code.

PubMed

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

2013-01-01

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

Disrupted regulatory T cell homeostasis in inflammatory bowel diseases

PubMed Central

Pedros, Christophe; Duguet, Fanny; Saoudi, Abdelhadi; Chabod, Marianne

2016-01-01

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20th century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population. PMID:26811641

Disrupted regulatory T cell homeostasis in inflammatory bowel diseases.

PubMed

Pedros, Christophe; Duguet, Fanny; Saoudi, Abdelhadi; Chabod, Marianne

2016-01-21

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.

Challenges and Opportunities for Tribal Waters: Addressing Disparities in Safe Public Drinking Water on the Crow Reservation in Montana, USA.

PubMed

Doyle, John T; Kindness, Larry; Realbird, James; Eggers, Margaret J; Camper, Anne K

2018-03-21

Disparities in access to safe public drinking water are increasingly being recognized as contributing to health disparities and environmental injustice for vulnerable communities in the United States. As the Co-Directors of the Apsaálooke Water and Wastewater Authority (AWWWA) for the Crow Tribe, with our academic partners, we present here the multiple and complex challenges we have addressed in improving and maintaining tribal water and wastewater infrastructure, including the identification of diverse funding sources for infrastructure construction, the need for many kinds of specialized expertise and long-term stability of project personnel, ratepayer difficulty in paying for services, an ongoing legacy of inadequate infrastructure planning, and lack of water quality research capacity. As a tribal entity, the AWWWA faces additional challenges, including the complex jurisdictional issues affecting all phases of our work, lack of authority to create water districts, and additional legal and regulatory gaps-especially with regards to environmental protection. Despite these obstacles, the AWWWA and Crow Tribe have successfully upgraded much of the local water and wastewater infrastructure. We find that ensuring safe public drinking water for tribal and other disadvantaged U.S. communities will require comprehensive, community-engaged approaches across a broad range of stakeholders to successfully address these complex legal, regulatory, policy, community capacity, and financial challenges.

Challenges and Opportunities for Tribal Waters: Addressing Disparities in Safe Public Drinking Water on the Crow Reservation in Montana, USA

PubMed Central

Doyle, John T.; Kindness, Larry; Realbird, James; Camper, Anne K.

2018-01-01

Disparities in access to safe public drinking water are increasingly being recognized as contributing to health disparities and environmental injustice for vulnerable communities in the United States. As the Co-Directors of the Apsaálooke Water and Wastewater Authority (AWWWA) for the Crow Tribe, with our academic partners, we present here the multiple and complex challenges we have addressed in improving and maintaining tribal water and wastewater infrastructure, including the identification of diverse funding sources for infrastructure construction, the need for many kinds of specialized expertise and long-term stability of project personnel, ratepayer difficulty in paying for services, an ongoing legacy of inadequate infrastructure planning, and lack of water quality research capacity. As a tribal entity, the AWWWA faces additional challenges, including the complex jurisdictional issues affecting all phases of our work, lack of authority to create water districts, and additional legal and regulatory gaps—especially with regards to environmental protection. Despite these obstacles, the AWWWA and Crow Tribe have successfully upgraded much of the local water and wastewater infrastructure. We find that ensuring safe public drinking water for tribal and other disadvantaged U.S. communities will require comprehensive, community-engaged approaches across a broad range of stakeholders to successfully address these complex legal, regulatory, policy, community capacity, and financial challenges. PMID:29561815

Convocation address.

PubMed

Swaminathan, M S

1998-07-01

This address delivered to the 40th convocation of the International Institute for Population Sciences in India in 1998 opens by noting that a shortage of jobs for youth is India's most urgent problem but that the problems that attend the increasing numbers of elderly also require serious attention. The address then notes that the Earth's population is growing at an unsustainable rate while economic inequities among countries are increasing, so that, while intellectual property is becoming the most important asset in developed countries, nutritional anemia among pregnant women causes their offspring to be unable to achieve their full intellectual potential from birth. Next, the address uses a discussion of the 18th-century work on population of the Marquis de Condorcet and of Thomas Malthus to lead into a consideration of estimated increased needs of countries like India and China to import food grains in the near future. Next, the progress of demographic transition in Indian states is covered and applied to Mahbub ul Haq's measure of human deprivation developed for and applied to the region of the South Asian Association for Regional Cooperation (India, Pakistan, Bangladesh, Nepal, Sri Lanka, Bhutan, and the Maldives). The address continues by reiterating some of the major recommendations forwarded by a government of India committee charged in 1995 with drafting a national population policy. Finally, the address suggests specific actions that could be important components of the Hunger-Free India Programme and concludes that all success rests on the successful implementation of appropriate population policies.

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.

Arabidopsis ensemble reverse-engineered gene regulatory network discloses interconnected transcription factors in oxidative stress.

PubMed

Vermeirssen, Vanessa; De Clercq, Inge; Van Parys, Thomas; Van Breusegem, Frank; Van de Peer, Yves

2014-12-01

The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation. © 2014 American Society of Plant Biologists. All rights reserved.

77 FR 32703 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... organization consents, the Commission shall either approve the proposed rule change, disapprove the proposed...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to Post-Trade Transparency for Agency Pass...

Innovations in vaccine development: can regulatory authorities keep up?

PubMed

Cox, Manon M J; Onraedt, Annelies

2012-10-01

Vaccine Production Summit San Francisco, CA, USA, 4-6 June 2012 IBC's 3rd Vaccine Production Summit featured 28 presentations discussing regulatory challenges in vaccine development, including the use of adjuvants, vaccine manufacturing and technology transfer, process development for vaccines and the role of quality by design, how to address vaccine stability, and how vaccine development timelines can be improved. The conference was run in parallel with the single-use applications for Biopharmaceutical Manufacturing conference. Approximately 250 attendees from large pharmaceutical companies, large and small biotech companies, vendors and a more limited number from academia were allowed to access sessions of either conference, including one shared session. This article summarizes the recurring themes across various presentations.

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...

Modeling positional effects of regulatory sequences with spline transformations increases prediction accuracy of deep neural networks

PubMed Central

Avsec, Žiga; Cheng, Jun; Gagneur, Julien

2018-01-01

Abstract Motivation Regulatory sequences are not solely defined by their nucleic acid sequence but also by their relative distances to genomic landmarks such as transcription start site, exon boundaries or polyadenylation site. Deep learning has become the approach of choice for modeling regulatory sequences because of its strength to learn complex sequence features. However, modeling relative distances to genomic landmarks in deep neural networks has not been addressed. Results Here we developed spline transformation, a neural network module based on splines to flexibly and robustly model distances. Modeling distances to various genomic landmarks with spline transformations significantly increased state-of-the-art prediction accuracy of in vivo RNA-binding protein binding sites for 120 out of 123 proteins. We also developed a deep neural network for human splice branchpoint based on spline transformations that outperformed the current best, already distance-based, machine learning model. Compared to piecewise linear transformation, as obtained by composition of rectified linear units, spline transformation yields higher prediction accuracy as well as faster and more robust training. As spline transformation can be applied to further quantities beyond distances, such as methylation or conservation, we foresee it as a versatile component in the genomics deep learning toolbox. Availability and implementation Spline transformation is implemented as a Keras layer in the CONCISE python package: https://github.com/gagneurlab/concise. Analysis code is available at https://github.com/gagneurlab/Manuscript_Avsec_Bioinformatics_2017. Contact avsec@in.tum.de or gagneur@in.tum.de Supplementary information Supplementary data are available at Bioinformatics online. PMID:29155928

76 FR 40150 - Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... Commission publishes its semiannual regulatory flexibility agenda. In addition, this document includes an...) requires each agency to publish twice each year a regulatory flexibility agenda containing a brief... 12866 requires each agency to publish twice each year a regulatory agenda of regulations under...

77 FR 55519 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

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2012-09-10

...\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to adopt existing NASD Interpretive Material... Policy The proposed rule change would replace several existing provisions in the Front Running Policy...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change...

78 FR 58580 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... proposed rule change, FINRA would no longer require a customer to elect one of the two existing panel...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change...,\\2\\ a proposed rule change amending the Code of Arbitration Procedure for Customer Disputes...

Addressing Passive Smoking in Children

PubMed Central

Hutchinson, Sasha G.; Kuijlaars, Jennifer S.; Mesters, Ilse; Muris, Jean W. M.; van Schayck, Constant P.; Dompeling, Edward; Feron, Frans J. M.

2014-01-01

Background A significant number of parents are unaware or unconvinced of the health consequences of passive smoking (PS) in children. Physicians could increase parental awareness by giving personal advice. Aim To evaluate the current practices of three Dutch health professions (paediatricians, youth health care physicians, and family physicians) regarding parental counselling for passive smoking (PS) in children. Methods All physicians (n = 720) representing the three health professions in Limburg, the Netherlands, received an invitation to complete a self-administered electronic questionnaire including questions on their: sex, work experience, personal smoking habits, counselling practices and education regarding PS in children. Results The response rate was 34%. One tenth (11%) of the responding physicians always addressed PS in children, 32% often, 54% occasionally and 4% reported to never attend to it. The three health professions appeared comparable regarding their frequency of parental counselling for PS in children. Addressing PS was more likely when children had respiratory problems. Lack of time was the most frequently mentioned barrier, being very and somewhat applicable for respectively 14% and 43% of the physicians. One fourth of the responders had received postgraduate education about PS. Additionally, 49% of the responders who did not have any education about PS were interested in receiving it. Conclusions Physicians working in the paediatric field in Limburg, the Netherlands, could more frequently address PS in children with parents. Lack of time appeared to be the most mentioned barrier and physicians were more likely to counsel parents for PS in children with respiratory complaints/diseases. Finally, a need for more education on parental counselling for PS was expressed. PMID:24809443

Regulatory considerations in the clinical development of vaccines indicated for use during pregnancy.

PubMed

Roberts, Jeffrey N; Gruber, Marion F

2015-02-18

Despite supportive public health policies (e.g., ACIP recommendations), the potential for providing clinical benefit through maternal immunization has yet to be fully realized. For vaccines already licensed and approved for use in adults, specific FDA approval for use during pregnancy to prevent disease in the mother and/or infant may have a significant impact on uptake and usage in pregnant women. In addition, for either a licensed vaccine or a novel vaccine, FDA approval for use during pregnancy would result in labeling that would serve as a resource for practitioners and would facilitate the safe and effective use of the vaccine during pregnancy. In the U.S., while many vaccines are approved for use in adults and most are not contraindicated for use in pregnant women, no vaccine is licensed for use specifically during pregnancy. Among the perceived obstacles hindering the clinical development of vaccines for use in pregnancy, regulatory issues are frequently cited. One aim of this article is to address the perceived regulatory obstacles. General concepts and regulatory considerations for clinical safety and effectiveness evaluations for vaccines indicated for use during pregnancy will be discussed. This discussion is not intended to establish data requirements or to articulate agency policy or guidance regarding specific vaccine products. Published by Elsevier Ltd.

An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation.

PubMed

You, Yanan; Cuevas-Diaz Duran, Raquel; Jiang, Lihua; Dong, Xiaomin; Zong, Shan; Snyder, Michael; Wu, Jia Qian

2018-06-12

Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms.

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

PubMed

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

2017-01-01

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

URISA Address Standard

EPA Pesticide Factsheets

The Urban and Regional Information Systems Association (URISA) standard for addresses. The document covers thoroughfare, landmark, and postal addresses within the United States, including its outlying territories and possessions.

Identifying and Addressing Themes of Job Dissatisfaction for Secondary Principals

ERIC Educational Resources Information Center

De Jong, David; Grundmeyer, Trent; Yankey, Julie

2017-01-01

Secondary principals serve in important roles that are complex, high-stress, and include demanding job responsibilities. Key stakeholders such as superintendents, school board members, and legislators must understand the challenges facing secondary principals in order to address the current themes of job dissatisfaction. Using new survey data…

75 FR 3760 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

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

75 FR 20645 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-20

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0158] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory... draft guide in the agency's ``Regulatory Guide'' series. This series was developed to describe and make...

76 FR 189 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

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

3 CFR - Regulatory Compliance

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Regulatory Compliance Presidential Documents Other Presidential Documents Memorandum of January 18, 2011 Regulatory Compliance Memorandum for the Heads of Executive Departments and Agencies My Administration is committed to enhancing effectiveness and efficiency in Government. Pursuant to the...

Emerging principles of regulatory evolution.

PubMed

Prud'homme, Benjamin; Gompel, Nicolas; Carroll, Sean B

2007-05-15

Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.

The limits of regulatory toxicology

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

Carrington, Clark D.; Bolger, P. Michael, E-mail: mike.bolger@fda.hhs.go

2010-03-01

The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standardsmore » are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.« less

Role of Sport Medicine Professionals in Addressing Psychosocial Aspects of Sport-Injury Rehabilitation: Professional Athletes' Views

PubMed Central

Arvinen-Barrow, Monna; Massey, William V.; Hemmings, Brian

2014-01-01

Context: Research from the sport medicine professional's (SMP's) perspective indicates that SMPs are often required to address psychosocial aspects of injuries during treatment. However, only a few authors have investigated injured athletes' experiences with these concerns. Objective: To explore injured professional athletes' views on the role of SMPs in the psychosocial aspects of sport-injury rehabilitation. Design Qualitative study. Setting: Professional association football and rugby union clubs. Patients or Other Participants: Ten professional, male football (n = 4; 40%) and rugby union (n = 6; 60%) players (age = 22.4 ± 3.4 years). Data Collection and Analysis We collected data using a semistructured interview guide, and the data were then transcribed and analyzed following the interpretative phenomenological analysis guidelines. We peer reviewed and triangulated the established emergent themes to establish trustworthiness. Results: Athletes in our study viewed injuries as “part and parcel” of their sports. Despite normalizing sport injuries, athletes reported frequent feelings of frustration and self-doubt throughout the rehabilitation process. However, athletes' perceived the role of SMPs in injury rehabilitation as addressing physical concerns; any intervention aimed at psychosocial outcomes (eg, motivation, confidence) needed to be subtle and indirect. Conclusions: The SMPs working with injured athletes need to understand the psychosocial principles that underpin athletes' sport-injury processes and the effect psychosocial reactions can have on athletes. Moreover, SMPs must understand the self-regulatory processes that may take place throughout injury rehabilitation and be able to apply psychological principles in natural and subtle ways to aid athletes' self-regulatory abilities. PMID:25243737

An address geocoding method for improving rural spatial information infrastructure

NASA Astrophysics Data System (ADS)

Pan, Yuchun; Chen, Baisong; Lu, Zhou; Li, Shuhua; Zhang, Jingbo; Zhou, YanBing

2010-11-01

The transition of rural and agricultural management from divisional to integrated mode has highlighted the importance of data integration and sharing. Current data are mostly collected by specific department to satisfy their own needs and lake of considering on wider potential uses. This led to great difference in data format, semantic, and precision even in same area, which is a significant barrier for constructing an integrated rural spatial information system to support integrated management and decision-making. Considering the rural cadastral management system and postal zones, the paper designs a rural address geocoding method based on rural cadastral parcel. It puts forward a geocoding standard which consists of absolute position code, relative position code and extended code. It designs a rural geocoding database model, and addresses collection and update model. Then, based on the rural address geocoding model, it proposed a data model for rural agricultural resources management. The results show that the address coding based on postal code is stable and easy to memorize, two-dimensional coding based on the direction and distance is easy to be located and memorized, while extended code can enhance the extensibility and flexibility of address geocoding.

Factors influencing physicians’ choice of workplace: systematic review of drivers of attrition and policy interventions to address them

PubMed Central

El Koussa, Maria; Atun, Rifat; Bowser, Diana; Kruk, Margaret E

2016-01-01

Objectives The movement of skilled physicians from the public to the private sector is a key constraint to achieving universal health coverage and is currently affecting health systems worldwide. This systematic review aims to assess factors influencing physicians’ choice of workplace, and policy interventions for retaining physicians in the public sector. Methods Five literature databases were searched. Studies were included in the review if they focused on at least one of the following criteria: (i) incentives or motivators for retaining physicians in the public sector, (ii) pull factors that encouraged physicians to move to the private sector, (iii) push factors that forced physicians to leave the public sector, (iv) policy interventions or case studies that addressed physician retention in the public sector, and (v) qualitative reviews of policy interventions that were implemented in different health system settings. Results Nineteen articles met the inclusion criteria. Six major themes that affected physicians’ choice of workplace were identified including: financial incentives, career development, infrastructure and staffing, professional work environment, workload and autonomy. The majority of the studies suggested that the use of financial incentives was a motivator in retaining physicians in the public sector. The review also identified policy interventions including: regulatory controls, incentives and management reforms. Regulatory controls and incentives were the two most frequently reported policy interventions. Conclusion While factors affecting physicians’ choice of workplace are country specific, financial incentives and professional development are core factors. Other factors are highly influenced by context, and thus, it would be useful for future cross–country research to use standardized data collection tools, allowing comparison of contextual factors as well as the examination of how context affects physician retention in the public

78 FR 21449 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... ``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to amend FINRA's Customer and Industry... arbitrator'' in the Codes. Specifically, the proposed rule change would (a) exclude persons associated with a...

78 FR 62784 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on a Proposed Rule Change Relating to Wash Sale Transactions and FINRA Rule...-4 thereunder,\\2\\ a proposed rule change to amend FINRA Rule 5210. The proposed rule change was...

77 FR 3019 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

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2012-01-20

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to Post-Trade Transparency for Agency Pass... 19b-4 thereunder,\\2\\ a proposed rule change related to post-trade transparency for agency pass-through...

75 FR 18241 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

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