Computational challenges in modeling gene regulatory events.

Science.gov (United States)

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.

Dioxins: diagnostic and prognostic challenges arising from complex mechanisms

DEFF Research Database (Denmark)

Rysavy, Noel M.; Maaetoft-Udsen, Kristina; Turner, Helen

2013-01-01

Dioxins are ubiquitous environmental challenges to humans, with a pervasiveness that arises from 200?years of rapid industrialization and mechanization of Western societies and which is now extending into the developing world. In spite of their penetrance of the human biota, these compounds...... such as cancer and diabetes, which are already multifactorial and highly complex, creates the context for the current review paper. Here, we summarize dioxin exposure paradigms and the resulting physiological effects that have been documented in animals and humans. Novel insights into potential endogenous end...... exogenous ligands, as well as the mechanisms by which these ligands impact acute and chronic cellular processes, are discussed. We develop the idea that the diagnosis of dioxin exposure, the subtleties of the cellular effects of the compounds and prognosis of the long-term effects of exposure are problems...

Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

International Nuclear Information System (INIS)

2011-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services

Regulatory challenges faced first Indonesia NPPs by independent TSOs

International Nuclear Information System (INIS)

Sri Budi Utami

2010-01-01

Technical and scientific support organizations (TSOs) dedicated to supporting national regulatory authorities. At present BAPETEN has internal TSOs. Pertaining to the regulatory control of nuclear safety, security, and safeguards for nuclear power plants (NPPs), independent TSOs providing support to the safety regulatory bodies are facing a number of technical challenges to ensuring the safety of NPPs. It is essential that BAPETEN need independent TSOs in order to warrant a sufficient level of safety, security and non proliferation in building and operating of first NPP. It is essential that BAPETEN need independent TSOs in order to warrant a sufficient level of safety, security and non proliferation in building and operating of first NPPs. (author)

Regulatory challenges for independent organization and licensing procedures for Egypt first nuclear power program

International Nuclear Information System (INIS)

Elsheikh, B.M.

2012-01-01

In March 2010 the Government of Egypt issued an Ordinance creating an independent regulatory body the Egypt Nuclear and Radiological Regulatory Authority (NRRA) reporting directly to the Prime Minister and responsible for matters dealing with protection of the radiation worker, public and environment from the harmful effects of ionizing radiation. A little more than 2 years have elapsed since this date. Some of the challenges faced by NRRA to its regulatory independence are given below. This paper will discuss the major challenges relating to Egyptian nuclear power program and specially the regulatory effectiveness and licensing procedures compared to international comparison.

Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

Science.gov (United States)

Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

2013-01-01

Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

IAEA Mission Says Chile Committed to Enhancing Safety, Sees Regulatory Challenges

International Nuclear Information System (INIS)

2018-01-01

An International Atomic Energy Agency (IAEA) team of experts said Chile is committed to strengthening its regulatory framework for nuclear and radiation safety. To help achieve this aim, the team said the country should address challenges in some areas, including the need to ensure effective independence in regulatory decision-making. The Integrated Regulatory Review Service (IRRS) team today concluded a 12-day mission to assess the regulatory safety framework in Chile. The mission was conducted at the request of the Government and hosted by the Chilean Nuclear Energy Commission (CCHEN), which is responsible for regulatory supervision together with the Ministry of Health (MINSAL). The review mission covered all civilian nuclear and radiation source facilities and activities regulated in Chile.

Nuclear regulatory decision making

International Nuclear Information System (INIS)

Wieland, Patricia; Almeida, Ivan Pedro Salati de

2011-01-01

The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

Regulatory Issues and Challenges in Preparing for the Regulation of New Reactor Siting: Malaysia's Experience

International Nuclear Information System (INIS)

Jais, Azlina Mohammad; Hassan, Halimah; Yasir, Muhamad Samudi; Roslan, Ridha

2011-01-01

This paper aims at giving an overview about the issues and challenges facing regulatory authority, the Atomic Energy Licensing Board (AELB) in ensuring nuclear safety, security and safeguards (3S's) and other relevant authorities to meet an impending nuclear power programme post-2020, in particular at the beginning stage of preparation for the regulation of nuclear power reactor siting. A comparison with an international framework and guidelines of the International Atomic Energy Agency (IAEA) and other countries' practice was made to get an overview of the present adequacy of Malaysia's nuclear regulatory framework in preparation for Malaysia to consider and perhaps decide for a safe, secure and peaceful nuclear power project in Malaysia, in utilising nuclear power in a quest for energy diversity and security. The important stage in the development of a nuclear power project is the evaluation of a suitable site to establish the site-related design inputs for the NPP. The evaluation of suitable site is the result of a process to ensure adequate protection of workers, public and the environment from the undue risk of ionizing radiation arising from NPP taking into account impact to the social communities and public acceptance, thus it will depend on the regulators to ensure a high level safety standards and security are met, in addition to its peaceful uses. Development of regulatory criteria for the site evaluation is a pre-initiatives licensing work for a possible nuclear power plant to performing effective nuclear safety and security reviews in an efficient and timely manner regardless whether Malaysia embarks on a nuclear power programme with anticipating challenges, learning from others' experiences in preparing for the demands for new licensing processes by collaborating internationally, in an expanding global environment

Bringing nanomedicines to market: regulatory challenges, opportunities, and uncertainties.

Science.gov (United States)

Nijhara, Ruchika; Balakrishnan, Krishna

2006-06-01

Scientists and entrepreneurs who contemplate developing nanomedicine products face several unique challenges in addition to many of the traditional hurdles of product development. In this review we analyze the major physicochemical, biologic and functional characteristics of several nanomedicine products on the market and explore the question of what made them unique. What made them successful? We also focus on the regulatory challenges faced by nanomedicine product developers. Based on these analyses, we propose the factors that are most likely to contribute to the success of nanomedicine products.

European regulatory tools for advanced therapy medicinal products.

Science.gov (United States)

Flory, Egbert; Reinhardt, Jens

2013-12-01

Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

Use of new scientific developments in regulatory risk assessments: challenges and opportunities.

Science.gov (United States)

Tarazona, Jose V

2013-07-01

Since the 1990s, science based ecological risk assessments constitute an essential tool for supporting decision making in the regulatory context. Using the European REACH Regulation as example, this article presents the challenges and opportunities for new scientific developments within the area of chemical control and environmental protection. These challenges can be sorted out in 3 main related topics (sets). In the short term, the challenges are directly associated with the regulatory requirements, required for facilitating a scientifically sound implementation of the different obligations for industry and authorities. It is important to mention that although the actual tools are different due to the regulatory requirements, the basic needs are still the same as those addressed in the early 1990s: understanding the ecological relevance of the predicted effects, including the uncertainty, and facilitating the link with the socio-economic assessment. The second set of challenges covers the opportunities for getting an added value from the regulatory efforts. The information compiled through REACH registration and notification processes is analyzed as source for new integrative developments for assessing the combined chemical risk at the regional level. Finally, the article discusses the challenge of inverting the process and developing risk assessment methods focusing on the receptor, the individual or ecosystem, instead of on the stressor or source. These approaches were limited in the past due to the lack of information, but the identification and dissemination of standard information, including uses, manufacturing sites, physical-chemical, environmental, ecotoxicological, and toxicological properties as well as operational conditions and risk management measures for thousands of chemicals, combined by the knowledge gathered through large scale monitoring programs and spatial information systems is generating new opportunities. The challenge is liking

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

Science.gov (United States)

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.

Threat ≠ prevention, challenge ≠ promotion: the impact of threat, challenge and regulatory focus on attention to negative stimuli.

Science.gov (United States)

Sassenberg, Kai; Sassenrath, Claudia; Fetterman, Adam K

2015-01-01

The purpose of the current experiment was to distinguish between the impact of strategic and affective forms of gain- and loss-related motivational states on the attention to negative stimuli. On the basis of the counter-regulation principle and regulatory focus theory, we predicted that individuals would attend more to negative than to neutral stimuli in a prevention focus and when experiencing challenge, but not in a promotion focus and under threat. In one experiment (N = 88) promotion, prevention, threat, or challenge states were activated through a memory task, and a subsequent dot probe task was administered. As predicted, those in the prevention focus and challenge conditions had an attentional bias towards negative words, but those in promotion and threat conditions did not. These findings provide support for the idea that strategic mindsets (e.g., regulatory focus) and hot emotional states (e.g., threat vs. challenge) differently affect the processing of affective stimuli.

The Future Regulatory Challenges of Liquidity Risk Management

OpenAIRE

Petr Teply

2011-01-01

Liquidity risk management ranks to key concepts applied in finance. Liquidity is defined as a capacity to obtain funding when needed, while liquidity risk means as a threat to this capacity to generate cash at fair costs. In the paper we present challenges of liquidity risk management resulting from the 2007- 2009 global financial upheaval. We see five main regulatory liquidity risk management issues requiring revision in coming years: liquidity measurement, intra-day and...

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

Science.gov (United States)

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.

Legitimacy challenges of intermediary gatekeeping in the Chinese internet regulatory system

NARCIS (Netherlands)

Wei, Lulu

2018-01-01

Legitimacy Challenges of Intermediary Gatekeeping in the Chinese Internet Regulatory System In the Chinese legal and political framework, in order for the government to maintain control over information posted on social media platforms, commercial internet intermediaries are assigned the role of

Construction and Operation of a Deep Geological Spent Fuel Repository in Sweden; Some Regulatory Aspects and Challenges

International Nuclear Information System (INIS)

Hedberg, Bengt

2014-01-01

The implementation of a deep geological spent fuel disposal concept in Sweden poses challenges on both implementer and regulator in many aspects. One such challenge is the application of the regulatory framework in a different situation compared to conventional process type nuclear facilities. A specific challenge in this regard is how to understand and address constraints from post-closure safety related to the construction and operation of the repository. The maybe most challenging aspect, however, is the unusually long time frame, i.e. many generations, for realization of the project. This paper addresses some of these challenges from a regulatory perspective. (authors)

77 FR 2556 - Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures; Public...

Science.gov (United States)

2012-01-18

...] Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures; Public Workshop... Administration (FDA), Office of Pediatric Therapeutics, is announcing a public workshop entitled ``Ethical and... provide a forum for careful consideration of scientific, ethical, and regulatory issues confronting FDA...

IAEA Mission Sees Significant Progress in Georgia’s Regulatory Framework, Challenges Ahead

International Nuclear Information System (INIS)

2018-01-01

An International Atomic Energy Agency (IAEA) team of experts said Georgia has made significant progress in strengthening its regulatory framework for nuclear and radiation safety. The team also pointed to challenges ahead as Georgia seeks to achieve further progress. The Integrated Regulatory Review Service (IRRS) team concluded a 10-day mission on 28 February to assess the regulatory safety framework in Georgia. The mission was conducted at the request of the Government and hosted by the Agency of Nuclear and Radiation Safety (ANRS), which is responsible for regulatory oversight in the country. IRRS missions are designed to strengthen the effectiveness of the national safety regulatory infrastructure, while recognizing the responsibility of each State to ensure nuclear and radiation safety. Georgia uses radioactive sources in medicine and industry and operates radioactive waste management facilities. It has decommissioned its only research reactor and has no nuclear power plants. In recent years, the Government and ANRS, with assistance from the IAEA, introduced new safety regulations and increased the number of regulatory inspections.

76 FR 66078 - Notice of Industry Workshop on Technical and Regulatory Challenges in Deep and Ultra-Deep Outer...

Science.gov (United States)

2011-10-25

...-0087] Notice of Industry Workshop on Technical and Regulatory Challenges in Deep and Ultra-Deep Outer... discussions expected to help identify Outer Continental Shelf (OCS) challenges and technologies associated... structured venue for consultation among offshore deepwater oil and gas industry and regulatory experts in...

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

Science.gov (United States)

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

2016-01-01

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

78 FR 56719 - Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of...

Science.gov (United States)

2013-09-13

...] Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Metabolic Diseases... announcing a public workshop entitled ``Changing Regulatory and Reimbursement Paradigms for Medical Devices... registration information on the AGA Web site. If you need special accommodations due to a disability, please...

Virtual Currencies – monetary policy dilemmas and regulatory challenges

Directory of Open Access Journals (Sweden)

Daj Alexis

2018-01-01

Full Text Available Although the topic of virtual currencies is not completely new, the current technological developments and the extent of the globalisation process appear to have changed the scope of the research efforts needed to cover not only the advantages and opportunities, but also the disadvantages and threats that the expansion of virtual currencies can pose for monetary policy and the safety of the financial system. This paper comprises a brief presentation of the different types of virtual currencies and identifies some of the most significant implications of large-scale virtual currency adoption for monetary authorities and regulators, while providing an overview of the main trends in the evolution of virtual currencies. In the end, one conclusion is evident: whatever monetary policy or regulatory issues arise from the use of virtual currencies, their consequences are far from virtual.

Regulatory challenges related to the licensing of a new nuclear power plant

International Nuclear Information System (INIS)

Maris, M.

2010-01-01

Assuring the safety and security of nuclear power plants is recognized world-wide as a challenge for all stakeholders. Particular attention goes to plants planned to be built in countries with not sufficiently developed industrial and regulatory infrastructure and experience. A construction and commissioning project, which is usually an international undertaking, gives opportunities to all national stakeholders to develop further their organisations and competences. In the present paper the duties of a regulatory body are recalled as well as the human resources and competences needed for the licensing of a new nuclear power plant. The regulatory body and its technical safety organization(s) should be strengthened and the international cooperation should contribute to this in a systematic and coordinated way. In particular, the donor country should support the necessary development of the regulatory competences and of an effective safety assessment process supporting the national licensing process. Appropriate support can be provided by the International Atomic Energy Agency (IAEA) and through other bi-lateral or multi-lateral programmes

Regulatory Body of Egypt: Practices and Challenges

International Nuclear Information System (INIS)

El-Messiry, A.

2016-01-01

In past, Egypt issued the law No. 59 of year 1969 for regulating the use of ionizing radiations inside the country, this law assigns the responsibilities of Egypt Atomic Energy Authority EAEA to control reactors, open sources, and all nuclear and radiation facilities inside its premises, while the ministry of health was responsible for controlling x-ray machine, sealed sources and accelerators. In 1982 EAEA established within its structure a new regulatory body called national centre for Nuclear Safety and radiation Control NC-NSRC as a dependent regulatory body, science EAEA is the operator of reactors and many nuclear and radiation facilities. On 30 March 2010 Egypt issued a nuclear law No 7 of year 2010, followed by its executive regulation in October 2011, the new law replaced the old law 59 of year 1969, in addition, the prime minster issued a decree on march 5td 2012 of establishing an independent regulatory body reported directly to him, it has the name of Egypt Nuclear and Radiological Regulatory Authority ENRRA, it is responsible for regulating all nuclear and radiation facilities and activities inside the country, except X-ray machines and linear accelerators for the medical uses, that still remains under the control of ministry of health. The new nuclear law defines the responsibility of the government to establish, support and determine the authorization and the responsibilities of the independent regulatory body. ENRRA is managed by a board of directors comprises from chairman, vice chairman, head of national security, interior, exterior, customs, export & import, standards, environment, justice organizations, besides two scientific experts from ENRRA. The board of council is the supreme authority of the dominant, and the conduct of ENRRA affairs, and take decisions within the framework of the national plan of Egypt, to achieve the objectives for which the ENRRA was established. ENRRA was organized from the old NC-NSRC staff into three regulatory

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

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

Science.gov (United States)

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.

Novel excipients - Regulatory challenges and perspectives - The EU insight.

Science.gov (United States)

Kozarewicz, Piotr; Loftsson, Thorsteinn

2018-05-21

Novel excipients are indispensable in development of modern, advanced drug delivery systems and biotechnology-derived drugs. Although numerous novel excipients are developed for pharmaceutical use, they are not frequently seen in medicinal products due to the strict regulatory requirements and perception that their use makes new product evaluation more complex with risk of delays in the approval process. Regulators regard novel excipients as new substances and whenever new excipient is used in a formulation it must be subjected to full evaluation, similarly to the one required for new active substance. Consequently, the amount of information required in support of the regulatory approval (i.e. marketing authorization) is much more complex and comprehensive than for established excipients. This short review provides an insight into the use of novel excipients in medicinal products approved in the European Union. In addition, barriers and challenges in development of novel excipients are being discussed as well as means to overcome those barriers. Copyright © 2018 Elsevier B.V. All rights reserved.

Regulatory challenges for GM crops in developing economies: the African experience.

Science.gov (United States)

Nang'ayo, Francis; Simiyu-Wafukho, Stella; Oikeh, Sylvester O

2014-12-01

Globally, transgenic or genetically modified (GM) crops are considered regulated products that are subject to regulatory oversight during trans-boundary movement, testing and environmental release. In Africa, regulations for transgenic crops are based on the outcomes of the historic Earth Summit Conference held in Rio, Brazil two decades ago, namely, the adoption of the Convention on Biological Diversity (CBD) and the subsequent adoption of the Cartagena Protocol on Biosafety. To exploit the potential benefits of transgenic crops while safeguarding the potential risks on human health and environment, most African countries have signed and ratified the CBD and the Cartagena Protocol on Biosafety. Consequently, these countries are required to take appropriate legal, administrative and other measures to ensure that the handling and utilization of living modified organisms are undertaken in a manner that reduces the risks to humans and the environment. These countries are also expected to provide regulatory oversight on transgenic crops through functional national biosafety frameworks (NBFs). While in principle this approach is ideal, NBFs in most African countries are steeped in a host of policy, legal and operational challenges that appear to be at cross-purposes with the noble efforts of seeking to access, test and deliver promising GM crops for use by resource-limited farmers in Africa. In this paper we discuss the regulatory challenges faced during the development and commercialization of GM crops based on experiences from countries in Sub-Saharan Africa.

Regulatory challenges of robotics : Some guidelines for addressing legal and ethical issues

NARCIS (Netherlands)

Leenes, Ronald; Palmerini, Erica; Koops, Bert-Jaap; Bertolini, Andrea; Salvini, Pericle; Lucivero, Federica

2017-01-01

Robots are slowly, but certainly, entering people’s professional and private lives. They require the attention of regulators due to the challenges they present to existing legal frameworks and the new legal and ethical questions they raise. This paper discusses four major regulatory dilemmas in the

Dealing with uncertainty arising out of probabilistic risk assessment

International Nuclear Information System (INIS)

Solomon, K.A.; Kastenberg, W.E.; Nelson, P.F.

1984-03-01

In addressing the area of safety goal implementation, the question of uncertainty arises. This report suggests that the Nuclear Regulatory Commission (NRC) should examine how other regulatory organizations have addressed the issue. Several examples are given from the chemical industry, and comparisons are made to nuclear power risks. Recommendations are made as to various considerations that the NRC should require in probabilistic risk assessments in order to properly treat uncertainties in the implementation of the safety goal policy. 40 references, 7 figures, 5 tables

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

Energy Technology Data Exchange (ETDEWEB)

Carter, Sarah R. [J. Craig Venter Inst., Rockville, MD (United States); Rodemeyer, Michael [Univ. of Virginia, Charlottesville, VA (United States); Garfinkel, Michele S. [EMBO, Heidelberg (Germany); Friedman, Robert M. [J. Craig Venter Inst., Rockville, MD (United States)

2014-05-01

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 for genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic

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

Science.gov (United States)

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

2013-08-01

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

Regulatory assessment of safety culture in nuclear organisations - current trends and challenges

International Nuclear Information System (INIS)

Tronea, M.

2010-01-01

The paper gives an overview of the current practices in the area of regulatory assessment of safety culture in nuclear organisations and of the associated challenges. While the assessment and inspection procedures currently in use by regulatory authorities worldwide are directed primarily at verifying compliance with the licensing basis, there is a recognised need for a more systematic approach to the identification, collection and review of data relevant to the safety culture in licensees' organisations. The paper presents a proposal for using the existing regulatory inspection practices for gathering information relevant to safety culture and for assessing it in an integrated manner. The proposal is based on the latest requirements and guidance issued by the International Atomic Energy Agency (IAEA) on management systems for nuclear facilities and activities, particularly as regards the attributes needed for a strong nuclear safety culture. (author)

Regulatory challenges in using nuclear operating experience

International Nuclear Information System (INIS)

2006-01-01

The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants in an acceptably safe manner at all times. Learning from experience has been a key element in meeting this objective. It is therefore very important for nuclear power plant operators to have an active programme for collecting, analysing and acting on the lessons of operating experience that could affect the safety of their plants. NEA experts have noted that almost all of the recent, significant events reported at international meetings have occurred earlier in one form or another. Counteractions are usually well-known, but information does not always seem to reach end users, or corrective action programmes are not always rigorously applied. Thus, one of the challenges that needs to be met in order to maintain good operational safety performance is to ensure that operating experience is promptly reported to established reporting systems, preferably international in order to benefit from a larger base of experience, and that the lessons from operating experience are actually used to promote safety. This report focuses on how regulatory bodies can ensure that operating experience is used effectively to promote the safety of nuclear power plants. While directed at nuclear power plants, the principles in this report may apply to other nuclear facilities as well. (author)

Regulatory forum opinion piece*: immunotoxicology assessments in nonhuman primates--challenges and opportunities.

Science.gov (United States)

Lebrec, Hervé N

2013-01-01

The immune system has been recognized for decades as a potential "target organ" of toxicity. Immune system activation can result in cytokine release resulting in severe systemic toxicity. Immunosuppression can result in impaired host defense and an increase in opportunistic infection, reemergence of latent infection, poor responses to vaccination, or increased risk of certain cancers. Several regulatory documents have addressed various aspects of immunotoxicity assessments. Nonhuman primates (NHPs) and in particular macaques are often the only relevant species for biotechnology-derived investigational new drugs based on cross-reactivity with human and NHP targets. This article reviews the challenges and opportunities associated with monitoring immune function in NHPs in the context of regulatory expectations. The article emphasizes how a comprehensive assessment of immunotoxicity remains a challenge due to interanimal variability associated with certain parameters (e.g., T-dependent antibody response)and it identifies gaps, such as the stage of development of certain assays (e.g., cytotoxic T-cell function). Despite these challenges, a thorough assessment of target biology-driven theoretical risks, in combination with proper integration of all information from the standard toxicology studies, and the refinement of certain assays should enable proper risk assessment. To this effect, emphasis should be placed on leveraging predictive in vitro assays using human cells.

Manufacturing, regulatory and commercial challenges of biopharmaceuticals production: a Finnish perspective.

Science.gov (United States)

Närhi, Marko; Nordström, Katrina

2005-04-01

Biopharmaceuticals product development is a broad and multidisciplinary field. Science and technology are combined with new manufacturing, regulatory and commercial challenges. However, although there is ample literature on the molecular biology and biochemistry of products, the implementation of processes from test tube to commercial scale has not received similar attention. Consequently, the present study aims to highlight, from practical point of view, some of the key issues involved with manufacturing technologies of biopharmaceuticals at a commercial scale. Regulatory requirements and investments are also addressed based on the practical experiences of start-up and small companies. Finland is used as a case-example of such companies as this is a EU-member state with strong technological growth and rapidly increasing number of biotech companies.

Global trade and assisted reproductive technologies: regulatory challenges in international surrogacy.

Science.gov (United States)

Nelson, Erin

2013-01-01

International surrogacy is an increasingly common phenomenon and an important global health challenge. Legal rules are a key consideration for the participants in international surrogacy arrangements. In some cases the law can help to resolve the complex issues that arise in this context, but it is important to consider the role played by law in contributing to the complex conflicts that such arrangements can generate. © 2013 American Society of Law, Medicine & Ethics, Inc.

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

Science.gov (United States)

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.

Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

Science.gov (United States)

Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

2016-07-01

Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Adoptive regulatory T cell therapy: challenges in clinical transplantation.

Science.gov (United States)

Safinia, Niloufar; Sagoo, Pervinder; Lechler, Robert; Lombardi, Giovanna

2010-08-01

The identification and characterisation of regulatory T cells (Tregs) has recently opened up exciting opportunities for Treg cell therapy in transplantation. In this review, we outline the basic biology of Tregs and discuss recent advances and challenges for the identification, isolation and expansion of these cells for cell therapy. Tregs of thymic origin have been shown to be key regulators of immune responses in mice and humans, preventing autoimmunity, graft-versus-host disease and organ graft rejection in the transplantation setting. To date, a variety of different methods to isolate and expand Tregs ex vivo have been advocated. Although promising, relatively few clinical trials of human Treg cell infusion have been initiated. Many key questions about Treg cell therapy still remain and here we provide an in-depth analysis and highlight the challenges and opportunities for immune intervention with Treg-based therapeutics in clinical transplantation.

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

Science.gov (United States)

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.

Regulatory challenges for the licensing of future nuclear plants: A public interest perspective

International Nuclear Information System (INIS)

Lyman, Edwin S.

2001-01-01

Regulatory challenges concerned with licensing of advanced NPPs must ensure that economic imperatives do not have adverse impacts on safety, risk of radiological sabotage, waste management and disposal, non-proliferation, full opportunity for public participation. This presentation explains the mentioned issues using pebble bed reactor as an example

The regulatory control of radiation sources in Australia -- The challenges of a federal system

International Nuclear Information System (INIS)

Loy, J.; Colgan, P.

2001-01-01

The report refers to the challenges that Australia is facing, as a federal nation having a Commonwealth Government and six States and two territories, in establishing appropriate regulatory control of radiation sources. Information on the national inventory of radiation sources and existing regulatory infrastructure, including the system of notification, registration, licensing, inspection and enforcement, is explained in the report. The national provisions for the management of disused sources; the planning, preparedness and response to abnormal events and emergencies; the recovery of control over orphan sources; and education and training; are specifically emphasized. (author)

Organic Coasts? Regulatory Challenges of Certifying Integrated Shrimp-Mangrove Production Systems in Vietnam

Science.gov (United States)

Ha, Tran Thi Thu; Bush, Simon R.; Mol, Arthur P. J.; van Dijk, Han

2012-01-01

The Vietnamese government aims to expand the scale of Naturland certified organic production in integrated shrimp-mangrove farming systems across the coast of Ca Mau province by 2015. In doing so the division between public and private regulation has become blurred. We analyze the government's goal by examining the regulatory challenges of using…

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

Science.gov (United States)

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

2016-01-01

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

Regulatory challenges in the management of aging of structural materials in nuclear power plants

International Nuclear Information System (INIS)

Castelo, C.; Mendoza, C.; Mas, E.; Conde, J. M.

2013-01-01

The article discusses two major pathways by which a regulatory body, and in particular the CSN, may participate in the acquisition of the necessary knowledge on mechanisms of aging of nuclear structural materials: to participate in forums to share operational experience and R and R project, both nationally and internationally. It notes the importance of this participation to carry out its regulatory function based on the knowledge acquired and the unique challenge of transferring that knowledge to rules and guidelines for their application. The article discusses various R and D projects in which the CSN participates directly. It calls for the presence of regulatory bodies in R and D project funded by the EU and the transfer of the results of such projects to codes, standards or guidelines for feasible implementation. (Author)

Nuclear security regulatory framework analysis for small modular reactors in Canada and abroad

Energy Technology Data Exchange (ETDEWEB)

Farah, A., E-mail: amjad.farah@uoit.ca [University of Ontario Institute of Technology, Oshawa, ON (Canada)

2015-07-01

Small Modular Reactors (SMRs) are gaining global attention as a potential solution for future power plants due to claims of flexibility and cost effectiveness, while maintaining or increasing safety and security. With the change of design and the potential deployment in remote areas, however, challenges arise from a regulatory standpoint, to meet the safety and security regulations while maintaining economic feasibility. This work comprises of a review of the nuclear security regulatory frameworks in place for SMRs in Canada, USA and the IAEA; how they compare to each other, and to those of large reactors. The goal is to gauge what needs to be adjusted in order to address the changes in design between the two reactor sizes. Some key challenges concern the type of reactor, transportation of reactor components and fuel to remote areas, reduced security staff, and increased complexity of emergency planning and evacuation procedures. (author)

Nuclear security regulatory framework analysis for small modular reactors in Canada and abroad

International Nuclear Information System (INIS)

Farah, A.

2015-01-01

Small Modular Reactors (SMRs) are gaining global attention as a potential solution for future power plants due to claims of flexibility and cost effectiveness, while maintaining or increasing safety and security. With the change of design and the potential deployment in remote areas, however, challenges arise from a regulatory standpoint, to meet the safety and security regulations while maintaining economic feasibility. This work comprises of a review of the nuclear security regulatory frameworks in place for SMRs in Canada, USA and the IAEA; how they compare to each other, and to those of large reactors. The goal is to gauge what needs to be adjusted in order to address the changes in design between the two reactor sizes. Some key challenges concern the type of reactor, transportation of reactor components and fuel to remote areas, reduced security staff, and increased complexity of emergency planning and evacuation procedures. (author)

Reduction of regulatory risk: a network economic approach

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2007-01-01

Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

Global regulatory developments for clinical stem cell research: diversification and challenges to collaborations.

Science.gov (United States)

Rosemann, Achim; Bortz, Gabriela; Vasen, Federico; Sleeboom-Faulkner, Margaret

2016-10-01

In this article, we explore regulatory developments in stem cell medicine in seven jurisdictions: Japan, China, India, Argentina, Brazil, the USA and the EU. We will show that the research methods, ethical standards and approval procedures for the market use of clinical stem cell interventions are undergoing an important process of global diversification. We will discuss the implications of this process for international harmonization and the conduct of multicountry clinical research collaborations. It will become clear that the increasing heterogeneity of research standards and regulations in the stem cell field presents a significant challenge to international clinical trial partnerships, especially with countries that diverge from the regulatory models that have been developed in the USA and the EU.

Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

Science.gov (United States)

Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

2015-07-01

To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

Medical revalidation as professional regulatory reform: Challenging the power of enforceable trust in the United Kingdom.

Science.gov (United States)

Spendlove, Zoey

2018-05-01

For more than two decades, international healthcare crises and ensuing political debates have led to increasing professional governance and regulatory policy reform. Governance and policy reforms, commonly representing a shift from embodied trust in professionals to state enforceable trust, have challenged professional power and self-regulatory privileges. However, controversy remains as to whether such policies do actually shift the balance of power and what the resulting effects of policy introduction would be. This paper explores the roll-out and operationalisation of revalidation as medical regulatory reform within a United Kingdom National Health Service hospital from 2012 to 2013, and its impact upon professional power. Revalidation policy was subject to the existing governance and management structures of the organisation, resulting in the formal policy process being shaped at the local level. This paper explores how the disorganised nature of the organisation hindered rather than facilitated robust processes of professional governance and regulation, fostering formalistic rather than genuine professional engagement with the policy process. Formalistic engagement seemingly assisted the medical profession in retaining self-regulatory privileges whilst maintaining professional power over the policy process. The paper concludes by challenging the concept of state enforceable trust and the theorisation that professional groups are effectively regulated and controlled by means of national and organisational objectives, such as revalidation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network.

Science.gov (United States)

Ali, Joseph; Califf, Robert; Sugarman, Jeremy

2016-01-01

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.

Gender-specific Regulatory Challenges to Product Approval: a panel discussion.

Science.gov (United States)

McGregor, Alyson J; Barr, Helen; Greenberg, Marna R; Safdar, Basmah; Wildgoose, Peter; Wright, David W; Hollander, Judd E

2014-12-01

On May 13, 2014, a 1-hour panel discussion session titled "Gender-specific Regulatory Challenges to Product Approval" was held during the Academic Emergency Medicine consensus conference, "Gender-specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." The session sought to bring together leaders in emergency medicine (EM) research, authors, and reviewers in EM research publications, as well as faculty, fellows, residents, and students engaged in research and clinical practice. A panel was convened involving a representative from the Office of Women's Health of the U.S. Food and Drug Administration, two pharmaceutical executives, and a clinical EM researcher. The moderated discussion also involved audience members who contributed significantly to the dialogue. Historical background leading up to the session along with the main themes of the discussion are reproduced in this article. These revolve around sex- and gender-specific research, statistical analysis of sex and gender, clinical practice, financial costs associated with pharmaceutical development, adaptive design, and specific recommendations on the regulatory process as it affects the specialty of EM. © 2014 by the Society for Academic Emergency Medicine.

Ethical and legal challenges in bioenergy governance: Coping with value disagreement and regulatory complexity

International Nuclear Information System (INIS)

Gamborg, Christian; Anker, Helle Tegner; Sandøe, Peter

2014-01-01

The article focuses on the interplay between two factors giving rise to friction in bioenergy governance: profound value disagreements (e.g. the prioritizing of carbon concerns like worries over GHG emissions savings over non-carbon related concerns) and regulatory complexity (in terms of regulatory measures and options). We present ethical and legal analyses of the current stalemate on bioenergy governance in the EU using two illustrative cases: liquid biofuels for transport and solid biomass-based bioenergy. The two cases disclose some similarities between these two factors, but the remaining differences may partly explain, or justify, contrasting forms of governance. While there seems to be no easy way in which the EU and national governments can deal with the multiple sustainability issues raised by bioenergy, it is argued that failure to deal explicitly with the underlying value disagreements, or to make apparent the regulatory complexity, clouds the issue of how to move forward with governance of bioenergy. We suggest that governance should be shaped with greater focus on the role of value disagreements and regulatory complexity. There is a need for more openness and transparency about such factors, and about the inherent trade-offs in bioenergy governance. - Highlights: • Ethical and legal challenges in governance of liquid biofuels and wood pellets. • EU sustainability criteria legal and ethical analysis—EU bioenergy policy options. • Analysis of interplay between carbon and non-carbon concerns and regulatory options. • Governance must cope with value disagreement and regulatory complexity

Regulatory control of the use of contractors by operating organizations. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

2000-09-01

This report arises from the eighth series of peer discussions on regulatory practices entitled 'Regulatory control of the use of contractors by operating organizations'. Senior regulators from 19 Member States participated in two peer group discussions in March 2000 and May 2000. This report gives an account of the outcomes of these meetings and of practical suggestions put forward by senior regulators. These suggestions do not necessarily reflect the views of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. The objective of this document is to share experience between regulatory bodies and provide practical suggestions for controlling the use of contractors and subcontractors by the operating organizations during all stages, especially operation, of a nuclear power plant, so as to ensure that the quality of work and services delivered is commensurate with the safety importance of the activities and that these are carried out in a manner that will not adversely affect the safe or reliable operation of the facility. These documented practical suggestions and experiences are the result of a series of peer discussions at the IAEA in 2000. It is considered that the manner in which control is exercised, and the various challenges connected to this control, are highly dependent upon the legislative framework, maturity of the nuclear programme, the size of the national nuclear industry and the culture in each country. The report is structured so that it covers the subject matter under the following main headings: Legal Provisions, Regulatory Strategy and Requirements; Regulatory Approaches for Controlling the Use of Contractors; Types of Contracts; Practical Suggestions

Female Regulatory Inspectors at Nuclear Power Plants: A Constant Challenge and Opportunities

International Nuclear Information System (INIS)

Maree, V.

2015-01-01

The South African National Nuclear Regulator (NNR) was established in 1999 to provide for the protection of persons, environment and properties from the harmful effects arising from ionizing radiation produced by radioactive materials. It is the responsibility of the licencee to have in place the necessary safety measures and resources in order to protect the public, workers and the environment against possible harmful effects of ionizing radiation caused by the operations of the Nuclear Power Stations. To fulfill its mission, the NNR employs 61 females with scientific and engineering qualifications to support and perform compliance assurance activities at the Nuclear Power Plant in accordance with the National Nuclear Regulator Act, 1999 (Act No. 47 of 1999). This Act describes the following in terms of duties of an inspector: “An Inspector may carry out inspections and use any applicable equipment during such inspections at any of the nuclear installations, sites or places and conduct such investigations as are necessary for the purpose of monitoring or enforcing compliance with this Act”. The Regulator has two offices, the Head office is located in Pretoria and the Site office is located in Cape Town. Regulatory Inspectors at the Site Office are responsible for performing compliance inspections at Nuclear Power Plant. Women at the Site office play an important role in fulfilling the mandate of the NNR, 3/5 inspectors are women. One is The Chief Inspector responsible for executing the compliance assurance programme and one of the female Inspectors is the South Africa Lead Representative at the International Atomic Energy Agency Waste Safety Standards Committee (IAEA–WASSC). This poster addresses the following challenges: – Plant facilities and personnel protective equipment, • Environment created by historical male domination, • Overcoming conscious and unconscious biases against women (by both genders). (author)

Regulatory T-cells in autoimmune diseases: challenges, controversies and--yet--unanswered questions.

Science.gov (United States)

Grant, Charlotte R; Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena

2015-02-01

Regulatory T cells (Tregs) are central to the maintenance of self-tolerance and tissue homeostasis. Markers commonly used to define human Tregs in the research setting include high expression of CD25, FOXP3 positivity and low expression/negativity for CD127. Many other markers have been proposed, but none unequivocally identifies bona fide Tregs. Tregs are equipped with an array of mechanisms of suppression, including the modulation of antigen presenting cell maturation and function, the killing of target cells, the disruption of metabolic pathways and the production of anti-inflammatory cytokines. Treg impairment has been reported in a number of human autoimmune conditions and includes Treg numerical and functional defects and conversion into effector cells in response to inflammation. In addition to intrinsic Treg impairment, resistance of effector T cells to Treg control has been described. Discrepancies in the literature are common, reflecting differences in the choice of study participants and the technical challenges associated with investigating this cell population. Studies differ in terms of the methodology used to define and isolate putative regulatory cells and to assess their suppressive function. In this review we outline studies describing Treg frequency and suppressive function in systemic and organ specific autoimmune diseases, with a specific focus on the challenges faced when investigating Tregs in these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Application of Regulation for recycling metals arising from Decommissioning of an Italian Nuclear Facility - Application of national regulations for metallic materials' recycling from the decommissioning of an Italian nuclear facility

International Nuclear Information System (INIS)

Varasano, Giovanni; Baldassarre, Leonardo; Petagna, Edoardo

2014-01-01

The start of the decommissioning of nuclear Italian sites requires proper management of clearance for large volumes of metallic materials. This paper describes the current legal framework relating to the Italian regulatory system of reference for the verification of the conditions of unconditional release of materials from nuclear installations, with particular reference to the recycling of metals. The definition of clearance levels, whether general or specific, ensures the clearance of materials arising from nuclear sites without further examinations. The Italian legislation on radiation protection requires that the removal of materials from authorized practices be subject to special requirements included in the authorization provisions. These requirements provide clearance levels that take account of the recommendations and technical guidelines supplied by the European Commission. The regulatory framework requires compliance with current technical and managerial requirements, issued by the National Regulatory Authority and annexed to the Ministerial Authorization, in which are shown the levels of surface activity and specific activity established for the unconditional release of metals from nuclear sites. The real challenge for the nuclear operator is the management of large amounts of waste materials arising from decommissioning activities. For the Italian operator SOGIN SpA is of extreme importance the correct application of national regulatory framework, in order to allow the most effective reduction of the amount of radioactive waste during decommissioning activities. (authors)

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

Regulatory Anatomy

DEFF Research Database (Denmark)

Hoeyer, Klaus

2015-01-01

This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

Ethics and Regulatory Challenges and Opportunities in Patient-Centered Comparative Effectiveness Research.

Science.gov (United States)

Sugarman, Jeremy

2016-04-01

The Affordable Care Act includes provisions for the conduct of large-scale, patient-centered comparative effectiveness research. Such efforts aim toward the laudable moral goal of having evidence to improve health care decision making. Nevertheless, these pragmatic clinical research efforts that typically pose minimal incremental risk and are enmeshed in routine care settings perhaps surprisingly encounter an array of ethics and regulatory challenges and opportunities for academic health centers. An emphasis on patient-centeredness forces an examination of the appropriateness of traditional methods used to protect the rights, interests, and welfare of participants. At the same time, meaningful collaboration with patients throughout the research process also necessitates ensuring that novel approaches to research (including recruitment and consent) entail necessary protections regarding such issues as privacy. As the scientific and logistical aspects of this research are being developed, substantial attention is being focused on the accompanying ethics and regulatory issues that have emerged, which should help to facilitate ethically appropriate research in a variety of contexts.

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

Science.gov (United States)

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.

Comprehensive genomic studies: emerging regulatory, strategic, and quality assurance challenges for biorepositories.

Science.gov (United States)

McDonald, Sandra A; Mardis, Elaine R; Ota, David; Watson, Mark A; Pfeifer, John D; Green, Jonathan M

2012-07-01

As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations.

Securing classification and regulatory approval for deepwater projects: management challenges in a global environment

Energy Technology Data Exchange (ETDEWEB)

Feijo, Luiz P.; Burton, Gareth C. [American Bureau of Shipping (ABS), Rio de Janeiro, RJ (Brazil)

2008-07-01

As the offshore industry continues to develop and move into increasingly deeper waters, technological boundaries are being pushed to new limits. Along with these advances, the design, fabrication and installation of deepwater oil and gas projects has become an increasingly global endeavor. After providing an overview of the history and role of Classification Societies, this paper reviews the challenges of securing classification and regulatory approval in a global environment. Operational, procedural and technological changes which one Classification Society; the American Bureau of Shipping, known as ABS, has implemented to address these challenges are presented. The result of the changes has been a more customized service aiming at faster and more streamlined classification approval process. (author)

Overcoming regulatory and economic challenges facing pharmacogenomics.

Science.gov (United States)

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviours

Directory of Open Access Journals (Sweden)

Daria eMolodtsova

2014-12-01

Full Text Available It is increasingly apparent that genes and networks that influence complex behaviour are evolutionary conserved, which is paradoxical considering that behaviour is labile over evolutionary timescales. How does adaptive change in behaviour arise if behaviour is controlled by conserved, pleiotropic, and likely evolutionary constrained genes? Pleiotropy and connectedness are known to constrain the general rate of protein evolution, prompting some to suggest that the evolution of complex traits, including behaviour, is fuelled by regulatory sequence evolution. However, we seldom have data on the strength of selection on mutations in coding and regulatory sequences, and this hinders our ability to study how pleiotropy influences coding and regulatory sequence evolution. Here we use population genomics to estimate the strength of selection on coding and regulatory mutations for a transcriptional regulatory network that influences complex behaviour of honey bees. We found that replacement mutations in highly connected transcription factors and target genes experience significantly stronger negative selection relative to weakly connected transcription factors and targets. Adaptively evolving proteins were significantly more likely to reside at the periphery of the regulatory network, while proteins with signs of negative selection were near the core of the network. Interestingly, connectedness and network structure had minimal influence on the strength of selection on putative regulatory sequences for both transcription factors and their targets. Our study indicates that adaptive evolution of complex behaviour can arise because of positive selection on protein-coding mutations in peripheral genes, and on regulatory sequence mutations in both transcription factors and their targets throughout the network.

Achievements and challenges in nuclear regulatory communication with the public. Outcome from the CNRA Workshops held in 2000, 2004 and 2007

International Nuclear Information System (INIS)

Joerle, Anders; Besenyei, Elisabeth; Calvo, Marina; Hah, Yeon-Hee; Hayden, Elizabeth; Herwig, Laurel; Kaliberda, Elena; Ostreng, Anne Marit; Robinson, Felicity; Storey, Peter; Yano, Mari; Zemanova, Dagmar; Chanial, Luc; Degueldre, Didier; Isaksson, Risto; Van Nuffelen, Dominique; Treier, Anton; Yoshimura, Uichiro; Gauvain, Jean

2008-06-01

the Public. NRO communication practices show that more and more common principles and practices for public communication about nuclear regulatory activity are now shared by OECD countries' nuclear regulators. Public Communication of NROs is clearly an area where the experience of the more advanced has been used to help the less advanced. Most OECD NRO have now a communication department or at least press officers, which reflects the fact that public communication is identified as integral part of the NROs mission. To this purpose NRO Communication Plans have been developed in many countries, which define the mission statement of the organisations, their communication strategy, their communication objectives and their communication targets. Conclusions of workshops and WGPC discussions have identified Stakeholder Involvement in nuclear safety as a necessary practice which helps enhance safety and support public confidence. It requires establish communication mechanisms and tools for discussions between the interested parties and those responsible for decision making. It has been highlighted that such a stakeholder involvement policy need dedicated resources to be efficiently implement. The use of the Internet has dramatically changed the audience of original documents and papers in allowing direct access to the public. In this respect, the development of Nuclear Regulators' web sites which have dramatically improved during this decade, allows that the interpretation and transfer of decisions and technical documents for the public are not only left to the media. This is a radical change in the possibility for directly communicating with the public and the ways to build confidence. Some challenges remain for the NROs such as how to develop an efficient and timely communication towards the public in case of a crisis, for instance when an event occurs in a nuclear facility. Another challenge is to set a proper balance between the need to strive for transparency and the

Licensing of Generic Medicines: Are There Any Challenges Left? A Pharmaceutical Regulatory Perspective.

Science.gov (United States)

Borg, John Joseph; Tomasi, Paolo; Pani, Luca; Aislaitner, George; Pirozynski, Michal; Leufkens, Hubert; Melchiorri, Daniela

2014-01-01

When an innovative product (innovator) is not covered anymore by intellectual property rights, cheaper equivalent medicinal products (generic products) may be marketed and used in clinical practice. The regulation of generic products is well-established, and is primarily based on standard rules for quality, therapeutic equivalence requirements (the latter in most instances proven through a bioequivalence study), and safety data for the innovator. The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy. While supporting this conclusion, there are a number of issues to be considered during the assessment of a generic product application. Six scenarios are described in total, from an efficacy and a safety perspective, where potential concerns with the current regulatory standards could arise in the approval of generic products. We also propose solutions to these scenarios in order to foster debate on these issues.

Challenges in developing TSO to provide technical support in nuclear safety and security to Pakistan Nuclear Regulatory Authority

International Nuclear Information System (INIS)

Mallick, Shahid A.; Sherwani, Uzman Habib; Mehdi, M. Ammar

2010-01-01

This paper highlights the needs for the establishment of a technical support organization (TSO) in Pakistan Nuclear Regulatory Authority (PNRA), challenges faced during its development, application of training need assessment required for the competency development of its technical manpower and difficulties encountered after its evolution. Key issues addressed include recruitment of technical manpower and enhancing their competencies, acquisition of proper tools required for safety review and assessment, development of a sustainable education and training program consistent with the best international practices and taking the measures to get confidence of the regulatory body. (author)

Exploring Temporal Sequences of Regulatory Phases and Associated Interactions in Low- and High-Challenge Collaborative Learning Sessions

Science.gov (United States)

Sobocinski, Márta; Malmberg, Jonna; Järvelä, Sanna

2017-01-01

Investigating the temporal order of regulatory processes can explain in more detail the mechanisms behind success or lack of success during collaborative learning. The aim of this study is to explore the differences between high- and low-challenge collaborative learning sessions. This is achieved through examining how the three phases of…

Translational and regulatory challenges for exon skipping therapies.

Science.gov (United States)

Aartsma-Rus, Annemieke; Ferlini, Alessandra; Goemans, Nathalie; Pasmooij, Anna M G; Wells, Dominic J; Bushby, Katerine; Vroom, Elizabeth; Balabanov, Pavel

2014-10-01

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.

Navigating the Challenges Arising from University-School Collaborative Action Research

Science.gov (United States)

Yuan, Rui; Mak, Pauline

2016-01-01

Despite increasing evidence showing the benefits language teachers can reap from university-school collaborative action research (CAR), scant attention has been given to how university researchers collaborate with language teachers, what challenges they might encounter, and how they navigate such challenges in CAR. To fill the gap, this study…

Removal of regulatory controls for materials and sites

International Nuclear Information System (INIS)

2004-01-01

Issues with the removal of regulatory controls are very important on the agenda of the regulatory authorities dealing with radioactive waste management (RWM). These issues arise prominently in decommissioning and in site remediation, and decisions can be very wide ranging having potentially important economic impacts and reaching outside the RWM area. The RWMC Regulators Forum started to address these issues by holding a topical discussion at its meeting in March 2003. Ths present document collates the national regulatory positions in the area of removal of regulatory controls. A summary of the national positions is also provided. The document is up to date to April 2004. (authors)

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

Science.gov (United States)

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 nuclear regulatory challenge of judging safety back fits

International Nuclear Information System (INIS)

2002-01-01

The economic pressures of electricity market competition have led nuclear power plant operators to seek ways to increase electricity production and to reduce operating costs at their plants. Corresponding pressures on the regulatory bodies include operator demand to reduce regulatory burdens perceived as unnecessary and general resistance to consider safety back-fits sought by the regulator. The purpose of this report is to describe potential situations giving rise to safety back-fit questions and to discuss regulatory approaches for judging the back-fits. The intended audience for this report is primarily nuclear regulators, although the information and ideas may also be of interest to nuclear operating organisations, other industry organisations and the general public. (author)

Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation.

Science.gov (United States)

Ponce, Rafael A

2011-01-01

Regulatory T-cell (T(reg)) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T(reg) modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T(reg) modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T(reg) and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T(reg) modulation, but not all, suggesting a continued need to explore and validate predictive models.

Regulatory challenges in using nuclear operating experience

International Nuclear Information System (INIS)

2006-01-01

There can be no doubt that the systematic evaluation of operating experience by the operator and the regulator is essential for continued safe operation of nuclear power plants. Recent concerns have been voiced that the operating experience information and insights are not being used effectively to promote safety. If these concerns foreshadow a real trend in OECD countries toward complacency in reporting and analysing operating events and taking corrective actions, then past experience suggests that similar or even more serious events will recur. This report discusses how the regulator can take actions to assure that operators have effective programmes to collect and analyse operating experience and, just as important, for taking steps to follow up with actions to prevent the events and conditions from recurring. These regulatory actions include special inspections of an operator operating experience programme and discussion with senior plant managers to emphasize the importance of having an effective operating experience programme. In addition to overseeing the operator programmes, the regulator has the broader responsibility for assuring that industry-wide trends, both national and international are monitored. To meet these responsibilities, the regulatory body must have its own operating experience programme, and this report discusses the important attributes of such regulatory programmes. It is especially important for the regulator to have the capability for assessing the full scope of operating experience issues, including those that may not be included in an operator operating experience programme, such as new research results, international operating experience, and broad industry trend information. (author)

47 CFR 1.1167 - Error claims related to regulatory fees.

Science.gov (United States)

2010-10-01

...) Challenges to determinations or an insufficient regulatory fee payment or delinquent fees should be made in writing. A challenge to a determination that a party is delinquent in paying a standard regulatory fee... 47 Telecommunication 1 2010-10-01 2010-10-01 false Error claims related to regulatory fees. 1.1167...

Role of partnership in enhancing the performance of radiation regulatory authority in Zambia

International Nuclear Information System (INIS)

Banda, S.C.

2003-01-01

The National Radiation Infrastructure includes legislation, human resource, technical capacity to execute responsibilities of the regulatory (1). In cases of developing countries like Zambia, special challenges arise in view of the constraints both in terms of human resource and funding. This paper will highlight same measures that may be undertaken to improve the operations of nation radiation protection infrastructure. The measures include collaboration with Science and Technology organisations that have technical capacity, delegation of responsible to key institutions that may have competence and generation of funds through training and provision of reliable quality service. (2). In Zambia, some achievements in this line have been registered by Radiation Protection Board working with the University of Zambia and National Institute for Scientific and Industrial Research (3). Some measures of generation of funds have been done though utilization of the generated remains to be the limiting factor to exploit fully benefits that may arise from the use of the monies generated from services. Partnerships with private sector may be used as regulatory authorities for support to its programme in particular the public awareness campaign. Sponsorship by a Private Cellar Phone Company (Telecel Zambia) and Rotary Club of Lusaka for Radiation Week to Radiation Protection Service under Theme 'Safe Radiation Use' is one such an example. The other opportunity is the technical cooperation with regional and international organisations such as SADC, IAEA, WHO, Interpol, EU and WCO for technical capacity building, human resource development and information access. (author)

Facing the challenge of stakeholders involvement: the Argentine nuclear regulatory case

International Nuclear Information System (INIS)

Acosta, Gabriela M.; Arnaud, Marta I.; Cesario, Pablo A.

2010-01-01

The Nuclear Regulatory Authority of Argentina (ARN) is an autonomous body reporting to the Presidency of Argentina, empowered to regulate and control the nuclear activity with regards to radiation and nuclear safety, physical protection and nuclear non-proliferation issues. Under the executive decree 1172/2003, which makes reference to the accessibility of public information to increase transparency of government actions and specially to promote public involvement, ARN has the legal obligation to inform of its activities in an accurate, comprehensive and understandable manner. The re-launching of the nuclear plan in 2006 and the repercussions this provoked on society highlighted the need to reinforce the legitimacy of the regulatory role and the promotion of confidence on its works to ensure the safety of the people. Therefore it was considered necessary to involve the society further in this programme by achieving greater public understanding and awareness of the nuclear regulatory activities. The more the public is conscious of the role of the regulator, conceiving it as a trustworthy and autonomous authority, the easier it is for the regulator to fulfil its obligations. As ARN has a strong commitment with society and considering that communication with the general public, as an external stakeholder, is a means to establishing and maintaining public trust and confidence, the implementation of a new communication programme became a key issue. In this scenario, ARN faced a challenge it was not prepared to handle and thus created a Division to deal with institutional communication and allow and ease the interaction with society. Within this Division, one of the methods chosen to achieve a better interaction with society was the use of a technological tool to attend possible inquiries, increasing and facilitating a greater involvement of the stakeholders. With this in mind a 'Mail-Info' was established because it allows a fast, accessible, easy and informal way of

Facing the challenge of stakeholders involvement: the Argentine nuclear regulatory case

Energy Technology Data Exchange (ETDEWEB)

Acosta, Gabriela M.; Arnaud, Marta I.; Cesario, Pablo A. [Nuclear Affairs and Institutional Communication Department, Autoridad Regulatoria Nuclear, Av. del Libertador 8250, C1429BNP (Argentina)

2010-07-01

The Nuclear Regulatory Authority of Argentina (ARN) is an autonomous body reporting to the Presidency of Argentina, empowered to regulate and control the nuclear activity with regards to radiation and nuclear safety, physical protection and nuclear non-proliferation issues. Under the executive decree 1172/2003, which makes reference to the accessibility of public information to increase transparency of government actions and specially to promote public involvement, ARN has the legal obligation to inform of its activities in an accurate, comprehensive and understandable manner. The re-launching of the nuclear plan in 2006 and the repercussions this provoked on society highlighted the need to reinforce the legitimacy of the regulatory role and the promotion of confidence on its works to ensure the safety of the people. Therefore it was considered necessary to involve the society further in this programme by achieving greater public understanding and awareness of the nuclear regulatory activities. The more the public is conscious of the role of the regulator, conceiving it as a trustworthy and autonomous authority, the easier it is for the regulator to fulfil its obligations. As ARN has a strong commitment with society and considering that communication with the general public, as an external stakeholder, is a means to establishing and maintaining public trust and confidence, the implementation of a new communication programme became a key issue. In this scenario, ARN faced a challenge it was not prepared to handle and thus created a Division to deal with institutional communication and allow and ease the interaction with society. Within this Division, one of the methods chosen to achieve a better interaction with society was the use of a technological tool to attend possible inquiries, increasing and facilitating a greater involvement of the stakeholders. With this in mind a 'Mail-Info' was established because it allows a fast, accessible, easy and informal

Regulatory challenges of historic uranium mines in Canada

International Nuclear Information System (INIS)

Clement, C.H.; Stenson, R.E.

2002-01-01

The radium and uranium mining industry began in Canada in 1930 with the discovery of the Port Radium deposit in the Northwest Territories. During the 1950s more uranium mines opened across Canada. Most of these mines ceased operation by the end of the 1960s. Some were remediated by their owners, while others were abandoned. The Atomic Energy Control Board (AECB), predecessor to the Canadian Nuclear Safety Commission (CNSC), was created in 1946. However, it was not until the mid-1970s that the AECB took an active role in regulating health, safety and environmental aspects of uranium mining; so many of the older mines have never been licensed. With the coming into force of the Nuclear Safety and Control Act (NSCA) in May 2000, this situation has been reviewed. The NSCA requires a licence for the possession of nuclear substances (including uranium mine tailings), or the decommissioning of nuclear facilities (including uranium mines and mills). Furthermore, governments (federal and provincial) are also subject to the NSCA, a change from the previous legislation. The CNSC has an obligation to assess these sites, regardless of ownership, and to proceed with licensing or other appropriate regulatory action. The CNSC has reviewed the status of the twenty sites in Canada where uranium milling took place historically. Eight are already licensed. Licensing actions are being pursued at the other sites. A review of nearly 100 small uranium mining or exploration sites is also underway to determine the most appropriate regulatory approach. This paper focuses on regulatory issues surrounding the historic mining and milling sites, and the regulatory approach being taken, including licensing provincial and federal government bodies who own some of the sites, and ensuring the safe management of sites that were abandoned. (author)

Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

Science.gov (United States)

Ram-Liebig, Gouya; Bednarz, Juergen; Stuerzebecher, Burkard; Fahlenkamp, Dirk; Barbagli, Guido; Romano, Giuseppe; Balsmeyer, Ulf; Spiegeler, Maria-Elsa; Liebig, Soeren; Knispel, Helmut

2015-03-01

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2013-01-01

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

International regulatory issues and approaches in the transition phase from operation to decommissioning

International Nuclear Information System (INIS)

Pyy, P.; Hrehor, M.; ); Murley, T.; Ranieri, R.; Laaksonen, J.

2005-01-01

Full text: The paper summarizes the work performed by an international group of senior nuclear safety regulators which was convened by the Committee on Nuclear Regulatory Activities (CNRA) of the OECD/Nuclear Energy Agency. The fundamental objective of this work was to identify the safety, environmental, organizational, human factors and public policy issues arising from decommissioning that will produce new challenges for the regulator. The study begins by recognizing that decommissioning is not simply an extension of operation and thus it is important for both the management of the facility and the regulator to understand the fundamental nature of the change taking place. Major regulatory policy issues discussed during this study include assurance of adequate funds, waste storage and disposal sites, material release criteria and site release criteria. Some of the important regulatory challenges relate to organizational and human factors, to safety and security requirements and to waste disposal and license termination. The importance of regular communication with both the corporate and site management and with public is recognized in the study as one of the key factors. When a nuclear facility ceases operation and enters into the decommissioning phase, both the operator and the regulator face a new set of challenges very different from those of an operating facility. The operator should have in place a strategic plan for decommissioning, prepared well in advance and reviewed by the regulatory body, to guide the facility managers and personnel through the changed circumstances. An essential part of the strategic plan should be the operator's plan for securing adequate funds to complete the decommissioning activities. In fact, the regulator should ensure that the operator sets aside funds, perhaps in a trust fund, while the facility is still operating and generating revenues. Both the operator and the regulator should expect a heightened public interest and concern

Survey of past base isolation applications in nuclear power plants and challenges to industry/regulatory acceptance

International Nuclear Information System (INIS)

Malushte, S.R.; Whittaker, A.S.

2005-01-01

Seismic base isolation provides many benefits that can facilitate the standardization of future nuclear power plant structures and equipment while reducing the initial/life-cycle cost and construction schedule. This paper presents a survey of past seismic base isolation applications and studies related to nuclear applications and provides a discussion of the challenges that need to be overcome to gain industry and regulatory acceptance for deployment in future US nuclear power plants. Issues related to design, codes/standards/regulations, procurement, and construction, have been identified. (authors)

Regulatory Powers in Public Procurement Law of Peruvian Administrative Agencies

Directory of Open Access Journals (Sweden)

Juan Carlos Morón Urbina

2017-12-01

Full Text Available Peruvian law has explicitly recognized regulatory powers to administrative agencies, which allows them to have a preponderant role in the production of rules in public procurement. Although these delegations of legislative authority are positively defined, distortions in the system of legal sources arise when agencies exceed delegated powers or when measures issued by administrative entities are mistaken for regulations. This paper aims to identify regulatory powers of Peruvian administrative agencies, as well as the regulatory measures they issue, and their relation with other sources of law.

Boundaries of regulatory fit: Is it the thought that counts?

DEFF Research Database (Denmark)

Leikas, S.; Lindeman, M.; Roininen, K.

2009-01-01

The feeling of regulatory fit is thought to arise from the right kind of goal pursuit, but some studies imply that it may be evoked even by lesser involvement in the right kind of strategies. The present experiment explored the minimum of involvement necessary to evoke regulatory fit. Participants...... the same information. Participants in promotion focus reported more positive attitudes in the rich information condition, whereas prevention-focused participants reported more positive attitudes in the accurate information condition. The results showed that regulatory fit can be evoked through mere thought...

Regional Power Integration : Structural and Regulatory Challenges

OpenAIRE

World Bank

2011-01-01

The Central America Regional Electricity Market (MER) trades electricity and transmission capacity among six Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama. The market differs from other electricity markets worldwide because it has its own regulatory body and system operator. Economic integration of the Central American countries has followed...

Correct fair market value calculation needed to avoid regulatory challenges.

Science.gov (United States)

Dietrich, M O

1997-09-01

In valuing a physician practice for acquisition, it is important for buyers and sellers to distinguish between fair market value and strategic value. Although many buyers would willingly pay for the strategic value of a practice, tax-exempt buyers are required by law to consider only the fair market value in setting a bid price. Valuators must adjust group earnings to exclude items that do not apply to any willing seller and include items that do apply to any willing seller to arrive at the fair market value of the practice. In addition, the weighted average cost of capital (WACC), which becomes the discount rate in the valuation model, is critical to the measure of value of the practice. Small medical practices are assumed to have few hard assets and little long-term debt, and the WACC is calculated on the basis of those assumptions. When a small practice has considerable debt, however, this calculated WACC may be inappropriate for valuing the practice. In every case, evidence that shows that a transaction has been negotiated "at arm's length" should stave off any regulatory challenge.

Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges.

Science.gov (United States)

Jossen, Valentin; van den Bos, Christian; Eibl, Regine; Eibl, Dieter

2018-05-01

Human mesenchymal stem cell (hMSC)-based therapies are of increasing interest in the field of regenerative medicine. As economic considerations have shown, allogeneic therapy seems to be the most cost-effective method. Standardized procedures based on instrumented single-use bioreactors have been shown to provide billion of cells with consistent product quality and to be superior to traditional expansions in planar cultivation systems. Furthermore, under consideration of the complex nature and requirements of allogeneic hMSC-therapeutics, a new equipment for downstream processing (DSP) was successfully evaluated. This mini-review summarizes both the current state of the hMSC production process and the challenges which have to be taken into account when efficiently producing hMSCs for the clinical scale. Special emphasis is placed on the upstream processing (USP) and DSP operations which cover expansion, harvesting, detachment, separation, washing and concentration steps, and the regulatory demands.

Evaluation of NORM in facility Venezuelan oil industry to establish regulatory criteria

International Nuclear Information System (INIS)

Acevedo Lozada, D. J.; Rivas, I.; Davila, L.; Flores, Y.

2013-01-01

The present work shows the need to identify, in the Venezuelan oil industry, the existence of exposure to natural sources of radiation should be considered as occupational. As Regulatory Authority in the area of ionizing radiation the need for regulatory processes and ensure radiation protection of personnel involved in these practices arises, as well as personal and environmental monitoring. NORM identifying an installation of the Venezuelan oil industry to establish regulatory processes and take steps to ensure occupational radiation protection. (Author)

Apocrine carcinoma arising in a complex fibroadenoma: a case report.

Science.gov (United States)

Mele, Marco; Vahl, Pernille; Funder, Jonas Amstrup; Sorensen, Anne Schmidt; Jensen, Vibeke

2014-01-01

A carcinoma arising in a fibroadenoma is a rare event, which often entails a diagnostic challenge. The most common type is the lobular carcinoma and secondary a ductal carcinoma. We present an extremely rare case of malignant development of an invasive apocrine carcinoma in a complex fibroadenoma and underline the importance for clinicians to recognize the possibility of benign and malignant co-existence especially in older women.

Perceptions of regulatory approaches

International Nuclear Information System (INIS)

Halin, Magnus; Leinonen, Ruusaliisa

2012-01-01

Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

Information transmission in genetic regulatory networks: a review

International Nuclear Information System (INIS)

Tkacik, Gasper; Walczak, Aleksandra M

2011-01-01

Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'. (topical review)

Everyday risk taking as a function of regulatory focus

NARCIS (Netherlands)

Hamstra, Melvyn R. W.; Bolderdijk, Jan Willem; Veldstra, Janet L.

Uncertainty is an inherent aspect of everyday life. However, faced with uncertainty, some individuals take risks more eagerly than others. Regulatory focus theory may explain such differences because risky behavior may arise naturally from the eagerness of promotion focused individuals, while safe

Challenges in orphan drug development and regulatory policy in China.

Science.gov (United States)

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.

Bitcoin: a regulatory nightmare to a libertarian dream

Directory of Open Access Journals (Sweden)

Primavera De Filippi

2014-05-01

Full Text Available This article provides an overview of national policies and current discussions on the regulation of bitcoin in Europe and beyond. After presenting the potential threat that cryptocurrencies pose to governmental and financial institutions worldwide, it discusses the regulatory challenges and the difficulty for national regulators to come up with a sound regulatory framework, which the author believes explains the current (lack of regulatory responses in this field. The article concludes that regulation is needed, but that in order not to excessively stifle innovation in this nascent ecosystem, some of these challenges might better be addressed through self-regulation.

75 FR 18202 - Notice of Indo-U.S. Regulatory Workshop

Science.gov (United States)

2010-04-09

... regulatory challenges faced by commissioners from both nations. The FERC Commissioners, along with other... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Indo-U.S. Regulatory Workshop April 1, 2010. Commissioner Philip D. Moeller will convene a workshop at the Federal Energy Regulatory...

Squamous Cell Carcinoma Arising in Mature Teratoma of the Ovary Masquerading as Abdominal Tuberculosis

Directory of Open Access Journals (Sweden)

Shreeya Taresh Indulkar

2018-01-01

Full Text Available Pure squamous cell carcinoma (SCC of the ovary is rare. SCC can arise in a mature teratoma (MT, ovarian endometriosis or in a Brenner tumor. SCC is the most common malignant transformation arising in MT and comprises 80% of all cases. Such neoplastic transformations are extremely difficult either to predict or detect early. The mechanism of malignant transformation has not been completely understood. Due to the rarity and the aggressive course, diagnosis and treatment constitute a big challenge. We report a case of SCC arising in MT presenting with a huge abdominopelvic mass and abundant peritoneal collections clinically masquerading as abdominal tuberculosis. A review of literature with special emphasis on prognosis and treatment modalities is also presented.

MAINTAINING LONG-TERM MANAGEMENT: Herbicide-resistant weeds challenge some signature cropping systems

Directory of Open Access Journals (Sweden)

Bradley D. Hanson

2014-10-01

Full Text Available Invasive and endemic weeds pose recurring challenges for California land managers. The evolution of herbicide resistance in several species has imposed new challenges in some cropping systems, and these issues are being addressed by UC Cooperative Extension farm advisors, specialists and faculty. There are currently 24 unique herbicide-resistant weed biotypes in the state, dominated by grasses and sedges in flooded rice systems and, more recently, glyphosate-resistant broadleaf and grass weeds in tree and vine systems, roadsides and glyphosate-tolerant field crops. Weed scientists address these complex issues using approaches ranging from basic physiology and genetics research to applied research and extension efforts in grower fields throughout the state. Although solutions to herbicide resistance are not simple and are affected by many biological, economic, regulatory and social factors, California stakeholders need information, training and solutions to address new weed management problems as they arise. Coordinated efforts conducted under the Endemic and Invasive Pests and Disease Strategic Initiative directly address weed management challenges in California's agricultural industries.

Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

Science.gov (United States)

Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

2017-11-01

In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

Network perturbation by recurrent regulatory variants in cancer.

Directory of Open Access Journals (Sweden)

Kiwon Jang

2017-03-01

Full Text Available Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.

Challenges in Establishing New Regulatory Body in Sri Lanka

International Nuclear Information System (INIS)

Hikkaduwa Liyanage, A.R.

2016-01-01

Sri Lanka's involvement with Nuclear Science and Technology began in 1957 when it became a member of the International Atomic Energy Agency. This was followed by the establishment of the Radioisotope Centre of the University of Colombo in 1962 and the establishment of the Atomic Energy Authority (AEA) in 1969 by the Atomic Energy Authority Act no. 19 of 1969. The Atomic Energy Authority Act delegated two main responsibilities to the AEA, namely, promotion of the utilization of nuclear technology for the benefit of the people of Sri Lanka, and protection of workers engaged in using radiation and radioisotopes and the public from harmful effects of ionizing radiation. Until 2014, the Atomic Energy Authority functioned as the national regulatory authority on use of radiation and radioisotopes, the national organization responsible for facilitating the use of nuclear technology in medical, industrial and agricultural sectors and as the focal point of the International Atomic Energy Agency in Sri Lanka. With the expansion of uses of radiation in Sri Lanka and commencement of use of high activity sources by the AEA for development and business activities, the need for an independent regulatory authority was realized. The importance of establishment of independent regulatory body for Sri Lanka was also emphasized by the IAEA in several advisory missions conducted in Sri Lanka and as results; a new Act on Atomic Energy was promulgated.

On-going and some future safety related activities of the OECD/NEA

International Nuclear Information System (INIS)

Frescura, G.

2001-01-01

The CSNI and CNRA structures and current activities of direct relevance to WWERs are presented. The nuclear regulatory challenges arising from economic deregulation like: direct safety challenges, infrastructure issues, increased pressure on regulatory bodies etc. are given. The OECD/NEA initiatives on assuring nuclear safety competence are mentioned

Development of measures to assess the safety of existing NPPs and the effectiveness of regulations and regulatory actions (including 'prescriptive' and 'performance based' approaches). Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1996-09-01

This report arises from the fourth series of peer discussions on regulatory practices entitled D evelopment of measures to assess the safety of existing nuclear power plants and the effectiveness of regulations and regulatory actions (including 'prescriptive' and 'performance based' approaches) . Senior regulators from 23 Member States participated in four peer group discussions during 1995-1996. This report presents the outcome of these meetings and recommendations of good practices identified by these senior regulators. The purpose of this report is to disseminate the views which the senior regulators presented at the meetings relating to measures used for assessing the safety of existing nuclear power plants and evaluating the effectiveness of regulators and regulatory actions. The intention in doing this is to assist Member States in the enhancement of their regulatory practices by identifying commonly accepted good practices. This report is structured so that it covers the subject matter under the following main headings: 'Prescriptive and Performance Based' Approaches to Regulation; Common Features of Regulatory Approaches; Effectiveness of the Regulator and Regulatory Actions; Recommendations of Good Practice. It is important to note that recommendations of good practice are included if they have been identified by at least one of the groups. It does not follow that all of the groups or individual Member States would necessarily endorse all of the recommendations. However, it is considered that if a single group of senior regulators judge that a particular practice is worthy of recommendation then it should be included for serious consideration. In some cases the same recommendations arise from all of the Groups

Regulatory challenges

International Nuclear Information System (INIS)

Austvik, Ole Gunnar

2003-01-01

The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability.

Science.gov (United States)

Hourd, Paul; Ginty, Patrick; Chandra, Amit; Williams, David J

2014-08-01

Manufacturing of more-than-minimally manipulated autologous cell therapies presents a number of unique challenges driven by complex supply logistics and the need to scale out production to multiple manufacturing sites or near the patient within hospital settings. The existing regulatory structure in Europe and the United States imposes a requirement to establish and maintain comparability between sites. Under a single market authorization, this is likely to become an unsurmountable burden beyond two or three sites. Unless alternative manufacturing approaches can be found to bridge the regulatory challenge of comparability, realizing a sustainable and investable business model for affordable autologous cell therapy supply is likely to be extremely demanding. Without a proactive approach by the regulators to close this "translational gap," these products may not progress down the development pipeline, threatening patient accessibility to an increasing number of clinician-led autologous cellular therapies that are already demonstrating patient benefits. We propose three prospective manufacturing models for the scale out/roll out of more-than-minimally manipulated clinically led autologous cell therapy products and test their prospects for addressing the challenge of product comparability with a selected expert reference panel of US and UK thought leaders. This paper presents the perspectives and insights of the panel and identifies where operational, technological and scientific improvements should be prioritized. The main purpose of this report is to solicit feedback and seek input from key stakeholders active in the field of autologous cell therapy in establishing a consensus-based manufacturing approach that may permit the roll out of clinically led autologous cell therapies. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

A global regulatory science agenda for vaccines.

Science.gov (United States)

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

Policy and Regulatory Challenges in the Tourism Collaborative Economy

DEFF Research Database (Denmark)

Dredge, Dianne

2017-01-01

The choice of policy approach and regulatory framework in dealing with the collaborative economy rests on two fundamental factors—that government decisions should be based on good sound knowledge and that this knowledge should be above politics. In the newly emerging and rapidly growing collabora......The choice of policy approach and regulatory framework in dealing with the collaborative economy rests on two fundamental factors—that government decisions should be based on good sound knowledge and that this knowledge should be above politics. In the newly emerging and rapidly growing......-sectors of the collaborative economy. However, these solutions are often based on assumptions about government sovereignty and power relations that do not necessarily apply in the slippery global world of platform capitalism. This chapter seeks to undertake a critical exploration of the factors and values that permeate...

Prediction of regulatory elements

DEFF Research Database (Denmark)

Sandelin, Albin

2008-01-01

Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

The Existing Regulatory Conditions for 'Energy Smart Water Utilities'

DEFF Research Database (Denmark)

Basse, Ellen Margrethe

2014-01-01

This chapter is focused on the legal conditions that exist for the energy–smart water utilities in the European Union (EU). In section 2 the interdependencies of water and energy services and the growing interest in solving these problems that may arise from this interdependence by regulatory ini...... legal design and the problems that it causes for the water utilities that want to be resource–efficient and have a low–carbon footprint.......This chapter is focused on the legal conditions that exist for the energy–smart water utilities in the European Union (EU). In section 2 the interdependencies of water and energy services and the growing interest in solving these problems that may arise from this interdependence by regulatory...... initiatives are shortly described. One of the solutions needed is a reduction of energy use in the water utilities by their utilisation of renewable sources – acting as energy–smart water utilities. Such utilities are described in section 3. The policy and law regulating the water utilities are important...

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

Science.gov (United States)

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.

Incident reporting to BfArM - regulatory framework, results and challenges.

Science.gov (United States)

Seidel, Robin; Stößlein, Ekkehard; Lauer, Wolfgang

2016-04-01

Medical devices are manifold and one of the most innovative fields of technology. As technologies advance, former limits cease to exist and complex devices become reality. Medical devices represent a very dynamic field with high economic relevance. The manufacturer of a medical device is obliged to minimize product-related risks as well as to demonstrate compliance with the so-called "essential requirements" regarding safety and performance before placing the device on the market. Any critical incident in relation to the application of a medical device has to be reported to the competent authority for risk assessment, which in Germany is either the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI) depending on the type of device. In this article, the German regulatory framework for medical devices and the resulting tasks for BfArM are described as well as the topics of its recently installed research and development group on prospective risk identification and application safety for medical devices. Results of failure mode and root cause analyses of incident data are presented as well as further data on cases with the result "root-cause analysis not possible". Finally an outlook is given on future challenges regarding risk assessment for medical devices.

Time-Line in HFEA Developments and Regulatory Challenges: 20 Years of Overseeing Fertility Practices and Research in the UK.

Science.gov (United States)

Agrawal, Rina; Burt, Elizabeth; Homburg, Roy

2013-12-01

In the wake of political upheaval, the Human Fertilisation and Embryo Authority (HFEA) has faced increasing insecurity over its future as a pivotal regulatory body of fertility practices in the UK. HFEA regulates activities by means of licensing, audit, and inspection of fertility centers and maintaining the Code of Practice, which ensures the optimum undertaking of licensed activities by fertility centers. In 2009, amendments to the 1990 Act came into force representing an amalgamation of cumulative proposals, debates, and changes in legislation, which have shaped the world of reproductive medicine. The medical world has, in many cases, adapted to righteous political and social demands, and continues to evolve at a rapid rate. The HFEA has faced many regulatory challenges and changes, and through this study, we aim to provide an overview of some of these changes, particularly those during the last 10 years and the implications that they may have had to fertility practices.

Challenges of atomic energy regulation in Indian context

International Nuclear Information System (INIS)

Bajaj, S.S.

2010-01-01

applications; -Developing competence in wide variety of technologies and different reactor designs; - Developing adequate human resource ready for safety supervision of this huge nuclear and radiation programme; - Approach to regulatory research related to new technologies. Apart from the above mentioned issues regulatory challenges may arise from policies to make all energy sectors competitive. With growing competition, it is becoming increasingly important to reconcile commercial interests with safety requirements. For AERB, the first challenge will be to ensure that economic pressures do not erode nuclear safety. To maintain highest level of safety culture, AERB will also need to adapt to an increasingly market-oriented environment and new working relationships with utilities. Although it is a difficult task, the Board has also evolved systematically over the years and now has an efficient structure, which is capable of facing the current challenges. (author)

Challenges in long-term operation of nuclear power plants - Implications for regulatory bodies

International Nuclear Information System (INIS)

Soda, Kunihisa; Van Wonterghem, Frederik; Khouaja, Hatem; Vilpas, Martti; Osouf, Nicolas; Harikumar, S.; Ishigaki, Hiroki; Osaki, Toru; Yamada, Tomoho; Carlsson, Lennart; Shepherd, David; Galloway, Melanie; Liszka, Ervin; Svab, Miroslav; Pereira, Ken; Huerta, Alejandro

2012-01-01

Nuclear power reactors have become a major source of electricity supply in many countries in the past half a century. Based on this experience, many operators have sought and have received authorisation for long-term operation, whereby plant operation continues beyond the period considered in the design of the plant. Acceptance of a nuclear power plant for extended service should be based on assurance of the fitness of the plant and the operator for safe and reliable operation over the entire period considered for long-term operation. This assurance may be obtained by establishment of appropriate regulatory requirements, specification of goals and safety levels and regulatory assessment and oversight of the operator's programme for long-term operation. The operators and regulators should ensure that operating experience continues to be evaluated during long-term operation to ensure that any relevant lessons are effectively applied. Other considerations for assurance of safe operation are effective management of ageing, possible need for safety improvements, application of lessons learnt from operating experience, evaluation of environmental impacts, adequate staff resources and performance, review of security at the plant, action in response to emerging issues, and openness and transparency in the transition to long-term operation. Even though most of these considerations are addressed under the regulatory framework that applies to the initial operating period, additional regulatory activities in these areas may be necessary for long-term operation. Although there can be significant differences in regulatory approaches used by different countries for evaluating acceptability of long-term operation, there is general agreement on the purposes and goals of the regulatory reviews. An authorisation of long-term operation could involve a licence renewal or a periodic safety review or an approach that melds elements of both. This report presents guidance that is intended

Emerging regulatory challenges facing the Indian rural electrification programme

International Nuclear Information System (INIS)

Bhattacharyya, Subhes C.; Srivastava, Leena

2009-01-01

The purpose of this paper is to present and analyse the regulatory issues emerging from the newly launched programme of rural electricity access in India. We focus on two broad areas, namely regulatory issues related to the organisation/structuring of the activities and issues related to subsidy and tariffs. The paper looks into the alternative organisational arrangements being used by the programme and identifies problem areas through a responsibility mapping. The tariff principle being followed by the programme is then analysed considering the alternative organisational forms and issues related to such pricing policies are identified. Possible alternative pricing options are then suggested. The paper finds that while the franchisee model is an innovative idea, it raises issues that the regulators should be concerned with. The programme has so far relied on the simplest franchisee model because of its ease of implementation but a transition to more complex alternatives would require careful considerations

76 FR 72220 - Incorporation of Risk Management Concepts in Regulatory Programs

Science.gov (United States)

2011-11-22

... actions? 4. What are the key characteristics for a holistic risk management regulatory structure for... accomplishing the goal of a holistic risk management regulatory structure? How could these challenges be... NUCLEAR REGULATORY COMMISSION [NRC-2011-0269] Incorporation of Risk Management Concepts in...

Integration of Bacterial Small RNAs in Regulatory Networks.

Science.gov (United States)

Nitzan, Mor; Rehani, Rotem; Margalit, Hanah

2017-05-22

Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.

Regulatory challenges for preventing firearms smuggling into Mexico

OpenAIRE

Vargas, Eugenio Weigend; González, Silvia Villarreal

2015-01-01

The recent surge in illegal firearms trafficking from the U.S. into Mexico has helped empower Mexican criminal groups to adopt highly confrontational strategies, contributing to a surge of violence throughout the country. This article addresses the regulatory asymmetries between Mexico and the U.S. with respect to the production, import, export, sales and possession of firearms. It reviews several important gun laws and explores why this asymmetry limits bilateral cooperation and encourages g...

Outsource Power, Import Safety? Challenges and Opportunities of the U.S.-China Food Safety Regulatory Cooperation.

Science.gov (United States)

Lin, Ching-Fu

The United States has a high stake in China’s serious food safety problem, as food products of Chinese origin have dominated the U.S. food market in numerous areas and continue to grow. The conclusion of the U.S.-China Food Safety Agreement (“the Agreement”) has allowed FDA to strengthen regulatory cooperation with its Chinese counterpart in various aspects. The Agreement also paves the way for the implementation of the new regulatory tools incorporated in FSMA, especially in the cross-border context. However, both the Agreement and FSMA have certain crucial limitations that may create future hurdles to effective implementation in the U.S.-China cooperation. This paper therefore endeavors to first examine China’s governance challenges over food safety, with a focus on the 2009 Food Safety Law, the 2015 Amendment, and the fundamental problem of “thin” rule of law. This paper moves to analyze the U.S.-China Food Safety Agreement, reviewing the agreement’s strengths and weaknesses. It further assesses FSMA’s innovative institutional design to regulate imported food products and its limitations. However, both the U.S.-China Food Safety Agreement and FSMA arguably create a regulatory dilemma for FDA when addressing imported food safety, due to structural mismatch between the broad scope of power granted to FDA and the long chain of power outsourcing to governments or private companies as primary “regulators.” Neither the Agreement nor FSMA give FDA adequate capacity to closely oversee such “agents” along the chain of power outsourcing. Framing the U.S.-China food safety cooperation as a multilayer structure that “outsources power” to “import safety,” this paper concludes by stressing the need for a robust accountability and effective mechanism for U.S.-China food safety cooperation.

Regulatory challenges affecting ICT development in Ukraine

DEFF Research Database (Denmark)

Kretova, Olga A.

2017-01-01

in the region in terms of network readiness (64th place out of 139 economies) and global competitiveness (79th place out of 140 economies) in 2016. The significance of ICT policies is broadly understood at the highest political level in Ukraine, however their implementation has always posed a challenge....... And the chapter is organized as follows. Section 2.1 is the introduction; section 2.2 presents an overview of policies and regulations influencing ICTs in Ukraine; section 2.3 presents a snapshot of the national ICT sector which is dominated by the mobile market and the Broadband Access Technology market; Section...... 2.4 provides an insight into the various ICT regulations, how it affected the markets and the challenges in implementing these policies; section 2.5 highlights the role , successes and challenges of implementing regulations aimed at implementing e-government; and section 2.7 concludes this chapter...

Opting out of the commercial use of nuclear power in Germany and challenges arising to nuclear supervision

International Nuclear Information System (INIS)

Renneberg, W.

2001-01-01

The governing majority in Germany has decided to opt out of the commercial use of nuclear power and to terminate this use in a safe and managed way. In the opinion of the federal government, the reasons for this decision include the potential for severe accidents, which is considered intolerable in the long run even though the probability of occurrence is low. In addition, there are the problems of final storage of radioactive waste, issues associated with the risk of proliferation, and the need to end a deep-seated societal conflict in Germany. In its function as the Top Regulator, the department responsible for nuclear matters of the Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU) has two important functions: It acts as the federal supervisor of the federal states which execute the Atomic Energy Act on behalf of the federal government, and it exercises the duty of preparing the nuclear policy outlined in the norms established by the federal government. After lengthy discussions with the operators of nuclear power plants an agreement was elaborated in preparation of a solution acceptable to all participants, which essentially defines an electricity quota for nuclear power plant operation and deals with spent fuel and nuclear waste management problems. This implies a number of challenges arising to the BMU as a consequence of the need to further ensure a high safety standard. It also means international efforts as well as the need to counteract the impending loss of competence in the nuclear field. (orig.) [de

[CD4 + CD25 + regulatory T cells and their importance to human illnesses].

Science.gov (United States)

Kelsen, Jens; Hvas, Christian Lodberg; Agnholt, Jørgen; Dahlerup, Jens F

2006-01-03

Regulatory T cells ensure a balanced immune response that is competent both to fight pathogens, at the same time, to recognize self-antigens and commensals as harmless. Regulatory mechanisms are essential in preventing autoimmune disorders but may also facilitate the progression of malignant diseases and the establishment of latent infections via suppression of the host immune response. Regulatory T cells arise in the thymus, and regulatory T cell function can be induced in the periphery, so-called infectious tolerance. An absolute or relative defect in regulatory T cell function may contribute to the development of autoimmune disorders such as rheumatoid arthritis, type 1 diabetes mellitus, multiple sclerosis and chronic inflammatory bowel disease. Regulatory T cell therapy is a tempting strategy for reestablishing the immune balance and thus preventing or reversing these disorders. Reestablishment of the immune balance may be accomplished by adoptive transfer of ex vivo-propagated regulatory T cells or by induction of regulatory functions locally in the organs, although such strategies are in their infancy in human research.

Applying quantitative benefit-risk analysis to aid regulatory decision making in diagnostic imaging: methods, challenges, and opportunities.

Science.gov (United States)

Agapova, Maria; Devine, Emily Beth; Bresnahan, Brian W; Higashi, Mitchell K; Garrison, Louis P

2014-09-01

Health agencies making regulatory marketing-authorization decisions use qualitative and quantitative approaches to assess expected benefits and expected risks associated with medical interventions. There is, however, no universal standard approach that regulatory agencies consistently use to conduct benefit-risk assessment (BRA) for pharmaceuticals or medical devices, including for imaging technologies. Economics, health services research, and health outcomes research use quantitative approaches to elicit preferences of stakeholders, identify priorities, and model health conditions and health intervention effects. Challenges to BRA in medical devices are outlined, highlighting additional barriers in radiology. Three quantitative methods--multi-criteria decision analysis, health outcomes modeling and stated-choice survey--are assessed using criteria that are important in balancing benefits and risks of medical devices and imaging technologies. To be useful in regulatory BRA, quantitative methods need to: aggregate multiple benefits and risks, incorporate qualitative considerations, account for uncertainty, and make clear whose preferences/priorities are being used. Each quantitative method performs differently across these criteria and little is known about how BRA estimates and conclusions vary by approach. While no specific quantitative method is likely to be the strongest in all of the important areas, quantitative methods may have a place in BRA of medical devices and radiology. Quantitative BRA approaches have been more widely applied in medicines, with fewer BRAs in devices. Despite substantial differences in characteristics of pharmaceuticals and devices, BRA methods may be as applicable to medical devices and imaging technologies as they are to pharmaceuticals. Further research to guide the development and selection of quantitative BRA methods for medical devices and imaging technologies is needed. Copyright © 2014 AUR. Published by Elsevier Inc. All rights

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

Science.gov (United States)

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

ATMPs for Cancer Immunotherapy: A Regulatory Overview.

Science.gov (United States)

Galli, Maria Cristina

2016-01-01

This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described.

Simulating Arctic clouds during Arctic Radiation- IceBridge Sea and Ice Experiment (ARISE)

Science.gov (United States)

Bromwich, D. H.; Hines, K. M.; Wang, S. H.

2015-12-01

The representation within global and regional models of the extensive low-level cloud cover over polar oceans remains a critical challenge for quantitative studies and forecasts of polar climate. In response, the polar-optimized version of the Weather Research and Forecasting model (Polar WRF) is used to simulate the meteorology, boundary layer, and Arctic clouds during the September-October 2014 Arctic Radiation- IceBridge Sea and Ice Experiment (ARISE) project. Polar WRF was developed with several adjustments to the sea ice thermodynamics in WRF. ARISE was based out of Eielson Air Force Base near Fairbanks, Alaska and included multiple instrumented C-130 aircraft flights over open water and sea ice of the Beaufort Sea. Arctic boundary layer clouds were frequently observed within cold northeasterly flow over the open ocean and ice. Preliminary results indicate these clouds were primarily liquid water, with characteristics differing between open water and sea ice surfaces. Simulated clouds are compared to ARISE observations. Furthermore, Polar WRF simulations are run for the August-September 2008 Arctic Summer Cloud Ocean Study (ASCOS) for comparison to the ARISE. Preliminary analysis shows that simulated low-level water clouds over the sea ice are too extensive during the the second half of the ASCOS field program. Alternatives and improvements to the Polar WRF cloud schemes are considered. The goal is to use the ARISE and ASCOS observations to achieve an improved polar supplement to the WRF code for open water and sea ice that can be provided to the Polar WRF community.

Confronting Ethical and Regulatory Challenges of Emergency Care Research With Conscious Patients.

Science.gov (United States)

Dickert, Neal W; Brown, Jeremy; Cairns, Charles B; Eaves-Leanos, Aaliyah; Goldkind, Sara F; Kim, Scott Y H; Nichol, Graham; O'Conor, Katie J; Scott, Jane D; Sinert, Richard; Wendler, David; Wright, David W; Silbergleit, Robert

2016-04-01

Barriers to informed consent are ubiquitous in the conduct of emergency care research across a wide range of conditions and clinical contexts. They are largely unavoidable; can be related to time constraints, physical symptoms, emotional stress, and cognitive impairment; and affect patients and surrogates. US regulations permit an exception from informed consent for certain clinical trials in emergency settings, but these regulations have generally been used to facilitate trials in which patients are unconscious and no surrogate is available. Most emergency care research, however, involves conscious patients, and surrogates are often available. Unfortunately, there is neither clear regulatory guidance nor established ethical standards in regard to consent in these settings. In this report-the result of a workshop convened by the National Institutes of Health Office of Emergency Care Research and Department of Bioethics to address ethical challenges in emergency care research-we clarify potential gaps in ethical understanding and federal regulations about research in emergency care in which limited involvement of patients or surrogates in enrollment decisions is possible. We propose a spectrum of approaches directed toward realistic ethical goals and a research and policy agenda for addressing these issues to facilitate clinical research necessary to improve emergency care. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Regional and International Networking to Support the Energy Regulatory Commission of Thailand

Energy Technology Data Exchange (ETDEWEB)

Lavansiri, Direk; Bull, Trevor

2010-09-15

The Energy Regulatory Commission of Thailand is a new regulatory agency. The structure of the energy sector; the tradition of administration; and, the lack of access to experienced personnel in Thailand all pose particular challenges. The Commission is meeting these challenges through regional and international networking to assist in developing policies and procedures that allow it to meet international benchmarks.

Regulatory Infrastructure for Radiation Safety and the Security of Radioactive Sources in Sudan, Present Status, Achievements and Future Challenges

International Nuclear Information System (INIS)

Osman, M.Y.

2008-01-01

Regulation of the use of ionizing radiation started formally in 1971 when an act has been issued by which the ministry of health was entitled to establish a Radiation Protection Technical Committee (RPTC) as a regulatory body. However, this act didn't come into effect because of the lack of regulations needed to execute the regulatory functions stated in that law. In 1972 the Sudan Atomic Energy Commission (SAEC) act was issued by which the commission was designated as a promoter for the use of nuclear technology. This law was later replaced by the 1996 act by which the Sudan Atomic Energy Corporation (SAEC) was established within the ministry of higher education and latter within the Ministry of Science and Technology (MOST). The board of the corporation established a technical committee (Radiation Protection Technical Committee (RPTC)) to carry out the regulatory functions assigned to the board by the act. The 1996 act didn't repeal the 1971 act; as a result, the two conflicting and overlapping acts are still valid. In 2003 the 1996 act was cancelled and to be replaced by an Order of Establishment within a general law for corporations in the Sudan. In spite of all these mess in providing a proper legislative framework, the RPTC (MOST) managed to secure a fair control of the use of radiation in different applications within the country. In this report, the current status of regulating the use of ionizing radiation as well as major challenges is described

Uterus transplantation: ethical and regulatory challenges.

Science.gov (United States)

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 system reform of occupational health and safety in China.

Science.gov (United States)

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.

Communication Regulatory Science: Mapping a New Field.

Science.gov (United States)

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

2017-12-13

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

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

Science.gov (United States)

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

Cross-border issues that arise in conjunction with the execution of U.S.-Canadian natural gas contracts

International Nuclear Information System (INIS)

Martin, J. G.

1999-01-01

Development of the U.S.-Canadian natural gas market as it is today and the issues that may arise in cross-border transactions involving natural gas contracts between the two countries are reviewed. In this context, the paper reviews recent history of U.S.-Canadian trade relations culminating in the development of NAFTA, the U.S. regulatory and legislative framework surrounding cross-border natural gas transactions, and general U.S. foreign trade policy that may come into play at the U.S.- Canada border. The paper also examines certain issues arising in the U.S. commercial context that may be of interest to Canadian corporations, specifically the U.S. Uniform Commercial Code, state jurisdiction on the U.S. side of the border, state and federal tax concerns, and the mechanics and potential benefits for a Canadian parent company in forming a U.S.-based subsidiary to handle U.S.-Canada natural gas transactions. 71 refs

Massive contribution of transposable elements to mammalian regulatory sequences.

Science.gov (United States)

Rayan, Nirmala Arul; Del Rosario, Ricardo C H; Prabhakar, Shyam

2016-09-01

Barbara McClintock discovered the existence of transposable elements (TEs) in the late 1940s and initially proposed that they contributed to the gene regulatory program of higher organisms. This controversial idea gained acceptance only much later in the 1990s, when the first examples of TE-derived promoter sequences were uncovered. It is now known that half of the human genome is recognizably derived from TEs. It is thus important to understand the scope and nature of their contribution to gene regulation. Here, we provide a timeline of major discoveries in this area and discuss how transposons have revolutionized our understanding of mammalian genomes, with a special emphasis on the massive contribution of TEs to primate evolution. Our analysis of primate-specific functional elements supports a simple model for the rate at which new functional elements arise in unique and TE-derived DNA. Finally, we discuss some of the challenges and unresolved questions in the field, which need to be addressed in order to fully characterize the impact of TEs on gene regulation, evolution and disease processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulatory control, nuclear safety regulation and waste management in Spain

International Nuclear Information System (INIS)

Martin, A.

2000-01-01

This article presents the challenges that faces the spanish regulatory authority. The deregulation of electricity industry imposes severe changes in nuclear power economics and forces nuclear power to compete with other sources of electricity. A pressure is perceived for regulatory effectiveness primarily since the cost of regulation is a component of the cost of the product. This effectiveness gain in regulatory control will be reached through systematic strategic analysis, formulation and implementation. The regulatory aspects of plant life extension and of waste management are examined

Categorization and selection of regulatory approaches for nuclear power plants

International Nuclear Information System (INIS)

Sugaya, Junko; Harayama, Yuko

2009-01-01

Several new regulatory approaches have been introduced to Japanese nuclear safety regulations, in which a prescriptive and deterministic approach had traditionally predominated. However, the options of regulatory approaches that can possibly be applied to nuclear safety regulations as well as the methodology for selecting the options are not systematically defined. In this study, various regulatory approaches for nuclear power plants are categorized as prescriptive or nonprescriptive, outcome-based or process-based, and deterministic or risk-informed. 18 options of regulatory approaches are conceptually developed and the conditions for selecting the appropriate regulatory approaches are identified. Current issues on nuclear regulations regarding responsibilities, transparency, consensus standards and regulatory inspections are examined from the viewpoints of regulatory approaches to verify usefulness of the categorization and selection concept of regulatory approaches. Finally, some of the challenges at the transitional phase of regulatory approaches are discussed. (author)

Regulatory system reform of occupational health and safety in China

Science.gov (United States)

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

Regulatory challenges in the management of aging of structural materials in nuclear power plants; Retos reguladores en la gestion del envejecimiento de los materiales estructurales de centrales nucleares

Energy Technology Data Exchange (ETDEWEB)

Castelo, C.; Mendoza, C.; Mas, E.; Conde, J. M.

2013-07-01

The article discusses two major pathways by which a regulatory body, and in particular the CSN, may participate in the acquisition of the necessary knowledge on mechanisms of aging of nuclear structural materials: to participate in forums to share operational experience and R and R project, both nationally and internationally. It notes the importance of this participation to carry out its regulatory function based on the knowledge acquired and the unique challenge of transferring that knowledge to rules and guidelines for their application. The article discusses various R and D projects in which the CSN participates directly. It calls for the presence of regulatory bodies in R and D project funded by the EU and the transfer of the results of such projects to codes, standards or guidelines for feasible implementation. (Author)

Regulatory practices for nuclear power plants in India

International Nuclear Information System (INIS)

Bajaj, S.S.

2013-01-01

The Atomic Energy Regulatory Board (AERB) is the national authority for ensuring that the use of ionizing radiation and nuclear energy does not cause any undue risk to the health of workers, members of the public and to the environment. AERB is responsible for the stipulation and enforcement of rules and regulations pertaining to nuclear and radiological safety. This paper describes the regulatory process followed by AERB for ensuring the safety of nuclear power plants (NPPs) during their construction as well as operation. This regulatory process has been continuously evolving to cater to the new developments in reactor technology. Some of the recent initiatives taken by AERB in this direction are briefly described. Today, AERB faces new challenges like simultaneous review of a large number of new projects of diverse designs, a fast growing nuclear power program and functioning of operating plants in a competitive environment. This paper delineates how AERB is gearing up to meet these challenges in an effective manner. (author)

Improving regulatory oversight of maintenance programs

International Nuclear Information System (INIS)

Cook, S.

2008-01-01

Safe nuclear power plant operation requires that risks due to failure or unavailability of Structures, Systems and Components (SSCs) be minimized. Implementation of an effective maintenance program is a key means for achieving this goal. In its regulatory framework, the important relationship between maintenance and safety is acknowledged by the CNSC. A high level maintenance program requirement is included in the Class I Facilities Regulations. In addition, the operating licence contains a condition based on the principle that the design function and performance of SSCs needs to remain consistent with the plant's design and analysis documents. Nuclear power plant licensees have the primary responsibility for safe operation of their facilities and consequently for implementation of a successful maintenance program. The oversight role of the Canadian Nuclear Safety Commission (CNSC) is to ensure that the licensee carries out that responsibility. The challenge for the CNSC is how to do this consistently and efficiently. Three opportunities for improvement to regulatory maintenance oversight are being pursued. These are related to the regulatory framework, compliance verification inspection activities and monitoring of self-reporting. The regulatory framework has been improved by clarifying expectations through the issuance of S-210 'Maintenance Programs for Nuclear Power Plants'. Inspection activities have been improved by introducing new maintenance inspections into the baseline program. Monitoring is being improved by making better use of self-reported and industry produced maintenance related performance indicators. As with any type of program change, the challenge is to ensure the consistent and optimal application of regulatory activities and resources. This paper is a summary of the CNSC's approach to improving its maintenance oversight strategy. (author)

Dynamics of the middle atmosphere as observed by the ARISE project

Science.gov (United States)

Blanc, E.

2015-12-01

It has been strongly demonstrated that variations in the circulation of the middle atmosphere influence weather and climate all the way to the Earth's surface. A key part of this coupling occurs through the propagation and breaking of planetary and gravity waves. However, limited observations prevent to faithfully reproduce the dynamics of the middle atmosphere in numerical weather prediction and climate models. The main challenge of the ARISE (Atmospheric dynamics InfraStructure in Europe) project is to combine existing national and international observation networks including: the International infrasound monitoring system developed for the CTBT (Comprehensive nuclear-Test-Ban Treaty) verification, the NDACC (Network for the Detection of Atmospheric Composition Changes) lidar network, European observation infrastructures at mid latitudes (OHP observatory), tropics (Maïdo observatory), high latitudes (ALOMAR and EISCAT), infrasound stations which form a dense European network and satellites. The ARISE network is unique by its coverage (polar to equatorial regions in the European longitude sector), its altitude range (from troposphere to mesosphere and ionosphere) and the involved scales both in time (from seconds to tens of years) and space (from tens of meters to thousands of kilometers). Advanced data products are produced with the scope to assimilate data in the Weather Prediction models to improve future forecasts over weeks and seasonal time scales. ARISE observations are especially relevant for the monitoring of extreme events such as thunderstorms, volcanoes, meteors and at larger scales, deep convection and stratospheric warming events for physical processes description and study of long term evolution with climate change. Among the applications, ARISE fosters integration of innovative methods for remote detection of non-instrumented volcanoes including distant eruption characterization to provide notifications with reliable confidence indices to the

Diversity and plasticity of Th cell types predicted from regulatory network modelling.

Directory of Open Access Journals (Sweden)

Aurélien Naldi

Full Text Available Alternative cell differentiation pathways are believed to arise from the concerted action of signalling pathways and transcriptional regulatory networks. However, the prediction of mammalian cell differentiation from the knowledge of the presence of specific signals and transcriptional factors is still a daunting challenge. In this respect, the vertebrate hematopoietic system, with its many branching differentiation pathways and cell types, is a compelling case study. In this paper, we propose an integrated, comprehensive model of the regulatory network and signalling pathways controlling Th cell differentiation. As most available data are qualitative, we rely on a logical formalism to perform extensive dynamical analyses. To cope with the size and complexity of the resulting network, we use an original model reduction approach together with a stable state identification algorithm. To assess the effects of heterogeneous environments on Th cell differentiation, we have performed a systematic series of simulations considering various prototypic environments. Consequently, we have identified stable states corresponding to canonical Th1, Th2, Th17 and Treg subtypes, but these were found to coexist with other transient hybrid cell types that co-express combinations of Th1, Th2, Treg and Th17 markers in an environment-dependent fashion. In the process, our logical analysis highlights the nature of these cell types and their relationships with canonical Th subtypes. Finally, our logical model can be used to explore novel differentiation pathways in silico.

78 FR 38053 - Regulatory Systems Strengthening

Science.gov (United States)

2013-06-25

... current state of medical product regulation globally, including challenges, risks, and emerging trends... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0010... product regulation; generation and analysis of evidence of regulatory systems performance; and provision...

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

Science.gov (United States)

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.

IAEA Mission Concludes Peer Review of Jordan's Nuclear Regulatory Framework

International Nuclear Information System (INIS)

2014-01-01

Senior international nuclear safety and radiation protection experts today concluded an 11-day International Atomic Energy Agency (IAEA) Integrated Regulatory Review Service (IRRS) mission to review the regulatory framework for nuclear and radiation safety in Jordan. The mission team said in its preliminary findings that Jordan's nuclear regulator, the Energy and Minerals Regulatory Commission (EMRC), faces challenges because it is a relatively new body that handles a high workload while also working to recruit, train and keep competent staff. The team also noted that a recent merger provided the regulator with more of the resources it needs to perform its duty. The team made recommendations and suggestions to the regulatory body and the Government to help them strengthen the effectiveness of Jordan's regulatory framework and functions in line with IAEA Safety Standards. The main observations of the IRRS Review team comprised the following: The regulatory body, founded in 2007 and merged with other regulators in April 2014 to form EMRC, faces large challenges in terms of its regulatory workload, management system building and staff recruitment and training; The new EMRC structure and revision of the radiation and nuclear safety law represents an important opportunity to strengthen Jordan's radiation and nuclear safety infrastructure; The Government has shown commitment to radiation and nuclear safety through measures including becoming party to international conventions. It could further demonstrate its commitment by adopting a formal national policy and strategy for safety that defines the role of the Minister of Energy in relation to EMRC and protects the independence of regulatory decision-making

Doing Qualitative Comparative Research on Teaching: Challenges and Benefits of Working with Grounded Theory

Science.gov (United States)

Rupp, Claudia

2016-01-01

The last decades have seen the completion of an increasing number of qualitative comparative research projects on teaching. Challenges and benefits which might arise from a qualitative international comparative research design have been considered. However, very little has been published on challenges and benefits which may arise from using…

Resilient Prosumer Scenario in a Changing Regulatory Environment—The UniRCon Solution

Directory of Open Access Journals (Sweden)

Mihai Sanduleac

2017-11-01

Full Text Available Technological developments are pushing for new solutions based upon massive integration of renewable electricity generation in networks already facing many challenges. This paper presents a novel approach to managing the energy transfer towards prosumers making use of smart management of local energy storage. The proposed design (including storage dimensioning is based on several operating scenarios in which the prosumer might operate as: (i a “load only” entity (from a grid perspective, thus exhibiting investment resiliency against regulatory changes and high energy efficiency; or (ii a prosumer, in case regulatory opportunistic profit might be available. This can be realized within a newly proposed Uni-directional Resilient Consumer (UniRCon architecture. The major aim of the proposed architecture is to achieve optimal self-consumption while avoiding curtailment even in a changing regulatory environment like, for example, the total lack of incentives for generation based on renewable energy sources (RES. One of the major advantages of the proposed architecture consists in the adaptability to changes in the regulatory and market environment. The term resilience is used with multiple meanings: (a the prosumer’s financial resilience against regulatory changes when investment calculations assume no-grid injections; (b the prosumer’s technical resilience, with electrical design based on standalone operation; (c the resilience of clusters of interconnected end-user installations with enabled community-level electricity exchange, independent of the existing main grid supply; (d the contribution to grid resilience, by enabling AC microgrid (MG operation in island mode when large portions of the grid are formed by clusters of UniRCon prosumers (the ease of islanding segmentation of the local grid in case of emergencies. For proof of concept, three use-cases are detailed: (i photovoltaic (PV installations connected behind the meter; (ii PV and

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

Science.gov (United States)

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

2013-11-01

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

Regulation of the life cycle of nuclear installations. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-06-01

This report arises from the sixth series of peer discussions on regulatory practices entitled 'Regulation of Life Cycle of Nuclear Installations'. Senior regulators from 18 Member States participated in three peer group discussions during 1997-1998. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the nominating organizations, or the IAEA. The purpose of this report is to disseminate the views which the senior regulators presented at the meetings relating to the policies, principles and requirements imposed by regulatory bodies for the safe management of the life cycle of a nuclear installation. The intention of doing this is to assist Member States in the formulation and enhancement of their regulatory control over PLCM by identifying commonly accepted good practices. This report is structured to cover the subject matter under the following main headings: Policies and Principles for the Life Cycle Management of Nuclear Installations; Responsibilities of the Regulatory Body and the Operating Organization; Requirements and Criteria Imposed by the Regulatory Body; Licensing and Regulatory Assessment for Plant Life Cycle Management; and Good Practices

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

Primary extradural meningioma arising from the calvarium

Directory of Open Access Journals (Sweden)

N Ravi

2013-06-01

Full Text Available Meningiomas are the most common intracranial tumours. Meningiomas arising at other locations are termed primary extradural meningiomas (EDM and are rare. Here we report a case of EDM arising from the calvarium – a primary calvarial meningioma (PCM.

Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines.

Science.gov (United States)

Hess, Ralf D; Weber, Friedemann; Watson, Keith; Schmitt, Siegfried

2012-04-05

In the development of novel substrates used for production of human vaccines there has been significant progress made in recent years. Emerging and re-emerging infectious diseases like the recent porcine Influenza A virus (H1N1) pandemic necessitated the availability of unprecedented amounts of vaccines. In addition, the high demand for vaccines in the industrialised countries has also been paralleled by a steep increase in demand in developing countries. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblasts, has now reached its capacity limit. This constraint may be overcome by utilising other recognised cell substrates such as Madin Darby Canine Kidney (MDCK) (dog origin), Chinese Hamster Ovary (CHO) (hamster cells) or Vero cells (monkey origin) or as an alternative, introduce new cell substrates of human or avian origin. Using new cell substrates may prove to be a highly replication-proficient way of producing live viral vaccines such as Influenza A viruses. Despite some advantages, cell substrates may pose a small residual risk to humans since some of them are known to be tumourigenic in immunosuppressed animals. However, this residual risk should be considered acceptable by regulators. Safety testing requirements for cell substrates used in the manufacture of vaccines is mandated by published guidance from organisations such as World Health Organization (WHO), United States Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Conferences on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) as well as requirements laid down in compendial monographs (Ph. Eur. and USP). This paper considers the guidance contained in these regulatory documents. In addition, the safety challenges and almost arbitrary risk-based classification of cell substrates used in the production of human

Telecommunications Reform in Nigeria: The Marketing Challenges ...

African Journals Online (AJOL)

Telecommunications Reform in Nigeria: The Marketing Challenges. ... Journal of Research in National Development ... This paper discusses the telecommunications reforms process, the role of the regulatory body (Nigeria Commission, the current state of the telecommunication sector and the marketing challenges in ...

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

Squamous cell carcinoma arising in an odontogenic cyst

International Nuclear Information System (INIS)

Yu, Jae Jung; Hwang, Eui Hwan; Lee, Sang Rae; Choi, Jeong Hee

2003-01-01

Squamous cell carcinoma arising in an odontogenic cyst is uncommon. The diagnosis of carcinoma arising in a cyst requires that there must be an area of microscopic transition from the benign epithelial cyst lining to the invasive squamous cell carcinoma. We report a histopathologically proven case of squamous cell carcinoma arising in a residual mandibular cyst in a 54-year-old woman.

Modular arrangement of regulatory RNA elements.

Science.gov (United States)

Roßmanith, Johanna; Narberhaus, Franz

2017-03-04

Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

Solitary Fibrous Tumor Arising from Stomach: CT Findings

Science.gov (United States)

Park, Sung Hee; Kwon, Jieun; Park, Jong-pil; Park, Mi-Suk; Lim, Joon Seok; Kim, Joo Hee; Kim, Ki Whang

2007-01-01

Solitary fibrous tumors are spindle-cell neoplasms that usually develop in the pleura and peritoneum, and rarely arise in the stomach. To our knowledge, there is only one case reporting a solitary fibrous tumor arising from stomach in the English literature. Here we report the case of a 26-year-old man with a large solitary fibrous tumor arising from the stomach which involved the submucosa and muscular layer and resembled a gastrointestinal stromal tumor in the stomach, based on what was seen during abdominal computed tomography. A solitary fibrous tumor arising from the stomach, although rare, could be considered as a diagnostic possibility for gastric submucosal tumors. PMID:18159603

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report

Energy Technology Data Exchange (ETDEWEB)

Kamran, Mudassar, E-mail: kamranm@mir.wustl.edu; Fowler, Kathryn J., E-mail: fowlerk@mir.wustl.edu; Mellnick, Vincent M., E-mail: mellnickv@mir.wustl.edu [Washington University School of Medicine, Mallinckrodt Institute of Radiology (United States); Sicard, Gregorio A., E-mail: sicard@wudosis.wustl.edu [Washington University School of Medicine, Department of Surgery (United States); Narra, Vamsi R., E-mail: narrav@mir.wustl.edu [Washington University School of Medicine, Mallinckrodt Institute of Radiology (United States)

2016-06-15

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.

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

Science.gov (United States)

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.

Strengthening of safety and security of radioactive sources: new regulatory challenges

Energy Technology Data Exchange (ETDEWEB)

El Messaoudi, M.; Essadki M Lferde, H.; Moutia, Z. [Faculte des Sciences, Dept. de Physique, Rabat (Morocco)

2006-07-01

The answer to these new regulatory challenges was given by implementation of divers measures aimed at strengthening of safety and security of radioactive sources and to prevent the malevolent use of radioactive sources. The international basic safety standards for protection against ionizing radiation and for the safety of radiation sources (B.S.S.) require the establishment and implementation of security measures of radioactive sources to ensure that protection and safety requirements are met. The IAEA has engaged in an extensive effort to establish and/or strengthen national radiation protection and radiological safety infrastructure, including legislation and regulation, a regulatory authority empowered to authorize and inspect regulated activities, an adequate number of trained personnel and technical services that are beyond the capabilities required of the authorized legal persons. The Moroccan authority makes steady efforts to strengthen national radiation safety infrastructure by participating in IAEA model project for upgrading radiation protection infrastructure, to implement the revised version of code of conduct on the safety and security of radioactive sources. Indeed, Morocco expressed its adhesion with the technical assistance project of the IAEA in 2001, carrying on the reinforcement of the national infrastructure of regulation and control of the radioactive materials. The control over radioactive sources is an essential element for maintaining high level of security and safety of radioactive sources. The IAEA T.E.C.-D.O.C.-1388 serves as reference document to implement the control culture. The security problems with which the world is confronted showed that the uses of radioactive sources should subject reinforcements of safety, of control and of security of the radioactive sources. For this purpose, the IAEA launched an action plan for the safety and security of radioactive sources. The IAEA guide Security of radioactive sources will help the

Strengthening of safety and security of radioactive sources: new regulatory challenges

International Nuclear Information System (INIS)

El Messaoudi, M.; Essadki M Lferde, H.; Moutia, Z.

2006-01-01

The answer to these new regulatory challenges was given by implementation of divers measures aimed at strengthening of safety and security of radioactive sources and to prevent the malevolent use of radioactive sources. The international basic safety standards for protection against ionizing radiation and for the safety of radiation sources (B.S.S.) require the establishment and implementation of security measures of radioactive sources to ensure that protection and safety requirements are met. The IAEA has engaged in an extensive effort to establish and/or strengthen national radiation protection and radiological safety infrastructure, including legislation and regulation, a regulatory authority empowered to authorize and inspect regulated activities, an adequate number of trained personnel and technical services that are beyond the capabilities required of the authorized legal persons. The Moroccan authority makes steady efforts to strengthen national radiation safety infrastructure by participating in IAEA model project for upgrading radiation protection infrastructure, to implement the revised version of code of conduct on the safety and security of radioactive sources. Indeed, Morocco expressed its adhesion with the technical assistance project of the IAEA in 2001, carrying on the reinforcement of the national infrastructure of regulation and control of the radioactive materials. The control over radioactive sources is an essential element for maintaining high level of security and safety of radioactive sources. The IAEA T.E.C.-D.O.C.-1388 serves as reference document to implement the control culture. The security problems with which the world is confronted showed that the uses of radioactive sources should subject reinforcements of safety, of control and of security of the radioactive sources. For this purpose, the IAEA launched an action plan for the safety and security of radioactive sources. The IAEA guide Security of radioactive sources will help the

Transcription regulatory networks analysis using CAGE

KAUST Repository

Tegnér, Jesper N.

2009-10-01

Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

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

Science.gov (United States)

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

Continuous improvement of the regulatory framework for the control of medical exposure

International Nuclear Information System (INIS)

Larcher, Ana M.; Ortiz Lopez, Pedro; Arias, Cesar; Marechal, Maria H.; Hernandez Alvarez, Ramon; Ferrer Garcia, Natividad; Castaneda Mucino, Antonia; Faller, Blanca

2008-01-01

One of the key elements to guide the improvement of the regulatory control is the availability of a self-assessment tool for regulatory performance. Although there is general guidance on self-assessment for regulators and users (IAEA), there is a need for more specific advice on how to address challenges and difficulties faced by regulatory bodies, when regulating radiation protection of patients. Examples of these challenges are the need for regulatory initiatives, in cooperation with health and education authorities, professional bodies and equipment suppliers, and to put in place necessary elements that are beyond responsibility of individual user of radiation, to enable them compliance with safety standards. Purpose: Within the programme of the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations, a project to develop such a self-assessment tool for the regulatory control of medical exposure has been designed. Method: National experiences in transposing and enforcing the international radiation safety standards, as to how the requirements are included in national regulations are reviewed. Further, difficulties to the implementation of safety requirements are analyzed and a self-assessment approach and possible regulatory solutions a are presented. Results and discussion: In this study the following documents are being produced: 1) transposition of international requirements into national regulations in the six countries of the Forum, 2) difficulties to implement and enforce the requirements, 3) guidance on self-assessment of regulatory framework for medical exposure, 4) suggested contribution to the revision of international radiation safety standards. (author)

Challenges for nuclear regulators

International Nuclear Information System (INIS)

Allen, M.R.

1994-01-01

The paper discusses issues that will present particular challenges to the nuclear industry, during the next decade, that should be addressed in order to achieve increased public acceptance of the industry. The issues of safety culture, peer review of safety, severe accidents, transport accidents and public communication are suggest as meriting special consideration. The need for nuclear regulatory agencies to establish credibility and for operating organisations to demonstrate accountability is emphasised, and the Australian experiences are reviewed. Increased collaboration by nuclear regulatory agencies in the Asian-pacific region is suggested, in order to encourage consistency of regulatory safety standards for the nuclear safety issues identified. Methods whereby this could be achieved within the framework of existing agreements and arrangements are suggested. 2 refs

Ownership options, financing structures, and regulatory considerations affecting independent power production projects

International Nuclear Information System (INIS)

Knapp, G.M.

1990-01-01

In this paper is a framework for analysis of the legal, financing, and policy differences between independent power production projects (IPPs) and projects with qualifying facility status (QFs) under the Public Utility Regulatory Policies Act (PURPA). At a basic level, there is no fundamental difference in types of ownership and financing structures available to IPPs and QFS. The key consideration, though, is the regulatory and legal implications to project participants. Significant issues arise for equity participants, lenders, developers, and project operators that are considering IPP projects. Of course, many of these same issues apply to certain types of QF projects that are not fully exempt from the Public Utility Holding Company Act (PUHCA) and the Federal Power Act (FPA)

Wilms tumor arising in extracoelomic paravertebral soft tissues.

LENUS (Irish Health Repository)

Mulligan, Linda

2012-02-01

Extrarenal Wilms tumor (ERWT) is a well-established entity which most commonly arises within the genitourinary tract, including intracoelomic paranephric soft tissue. Rarely, ERWT arises within teratoma, and it tends to occur predominantly in distinct settings, such as females with spinal defects and males with testicular teratomas. We report a unique ERWT arising within an extracoelomic teratoma of the paraspinal musculature, thereby expanding the range of reported locations for this unusual tumor.

Systematic identification of regulatory variants associated with cancer risk.

Science.gov (United States)

Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

2017-10-23

Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

Esophageal leiomyoma arising in an epiphrenic diverticulum

International Nuclear Information System (INIS)

Hamilton, S.

1988-01-01

A 32-year old woman was found at surgery to have an esophageal leiomyoma arising within an epiphrenic diverticulum. These uncommon conditions may rarely occur together, causing difficulty in diagnosis of the leiomyoma. Other neoplasms may also arise in an epiphrenic diverticulum and should be borne in mind in this situation. (orig.)

Validation of innovative technologies and strategies for regulatory safety assessment methods: challenges and opportunities.

Science.gov (United States)

Stokes, William S; Wind, Marilyn

2010-01-01

Advances in science and innovative technologies are providing new opportunities to develop test methods and strategies that may improve safety assessments and reduce animal use for safety testing. These include high throughput screening and other approaches that can rapidly measure or predict various molecular, genetic, and cellular perturbations caused by test substances. Integrated testing and decision strategies that consider multiple types of information and data are also being developed. Prior to their use for regulatory decision-making, new methods and strategies must undergo appropriate validation studies to determine the extent that their use can provide equivalent or improved protection compared to existing methods and to determine the extent that reproducible results can be obtained in different laboratories. Comprehensive and optimal validation study designs are expected to expedite the validation and regulatory acceptance of new test methods and strategies that will support improved safety assessments and reduced animal use for regulatory testing.

The future regulatory environment - a South African perspective

International Nuclear Information System (INIS)

Van der Woude, S.; Leaver, J.; Metcalf, P.E.

2000-01-01

The South African nuclear regulatory authority, the National Nuclear Regulator, regulates nuclear fuel cycle facilities as well as a large variety of mining and minerals processing activities. The future political, social, economical and technological environment, within which these facilities operate, will present numerous challenges to those who will be regulating them. In our presentation the challenges to be fulfilled in discharging the regulatory function are discussed, particularly in the context of a country with a small nuclear programme and a substantial developing component. Amongst the challenges discussed are: As part of the growing internationalization, the need to harmonize standards applied in different countries and the need to balance standards and practice applied in developed countries with resources available in developing countries; The need to consider the impact on the environment and not only on human beings; The impact of rapid advances in information technology on regulation; The maintenance and development of the appropriate expertise in the face of uncertainties regarding the future of the nuclear industry; Public involvement; The demands by society for greater standards of safety but at the same time for more effective and cost-effective regulation; The need for regulators to match customer demands on operators in terms of quality, speed, flexibility and costs; The privatization of nuclear fuel cycle facilities; The increased trend for larger facilities to outsource work to smaller companies; and, The need to balance good practice considerations with quantitatively determined risks in regulatory decision-making. (author)

The future regulatory environment - a South African perspective

Energy Technology Data Exchange (ETDEWEB)

Van der Woude, S.; Leaver, J.; Metcalf, P.E. [National Nuclear Regulator, Centurion (South Africa)

2000-07-01

The South African nuclear regulatory authority, the National Nuclear Regulator, regulates nuclear fuel cycle facilities as well as a large variety of mining and minerals processing activities. The future political, social, economical and technological environment, within which these facilities operate, will present numerous challenges to those who will be regulating them. In our presentation the challenges to be fulfilled in discharging the regulatory function are discussed, particularly in the context of a country with a small nuclear programme and a substantial developing component. Amongst the challenges discussed are: As part of the growing internationalization, the need to harmonize standards applied in different countries and the need to balance standards and practice applied in developed countries with resources available in developing countries; The need to consider the impact on the environment and not only on human beings; The impact of rapid advances in information technology on regulation; The maintenance and development of the appropriate expertise in the face of uncertainties regarding the future of the nuclear industry; Public involvement; The demands by society for greater standards of safety but at the same time for more effective and cost-effective regulation; The need for regulators to match customer demands on operators in terms of quality, speed, flexibility and costs; The privatization of nuclear fuel cycle facilities; The increased trend for larger facilities to outsource work to smaller companies; and, The need to balance good practice considerations with quantitatively determined risks in regulatory decision-making. (author)

Solitary Fibrous Tumor Arising from Stomach: CT Findings

OpenAIRE

Park, Sung Hee; Kim, Myeong-Jin; Kwon, Jieun; Park, Jong-pil; Park, Mi-Suk; Lim, Joon Seok; Kim, Joo Hee; Kim, Ki Whang

2007-01-01

Solitary fibrous tumors are spindle-cell neoplasms that usually develop in the pleura and peritoneum, and rarely arise in the stomach. To our knowledge, there is only one case reporting a solitary fibrous tumor arising from stomach in the English literature. Here we report the case of a 26-year-old man with a large solitary fibrous tumor arising from the stomach which involved the submucosa and muscular layer and resembled a gastrointestinal stromal tumor in the stomach, based on what was see...

Inferring regulatory networks from expression data using tree-based methods.

Directory of Open Access Journals (Sweden)

Vân Anh Huynh-Thu

2010-09-01

Full Text Available One of the pressing open problems of computational systems biology is the elucidation of the topology of genetic regulatory networks (GRNs using high throughput genomic data, in particular microarray gene expression data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM challenge aims to evaluate the success of GRN inference algorithms on benchmarks of simulated data. In this article, we present GENIE3, a new algorithm for the inference of GRNs that was best performer in the DREAM4 In Silico Multifactorial challenge. GENIE3 decomposes the prediction of a regulatory network between p genes into p different regression problems. In each of the regression problems, the expression pattern of one of the genes (target gene is predicted from the expression patterns of all the other genes (input genes, using tree-based ensemble methods Random Forests or Extra-Trees. The importance of an input gene in the prediction of the target gene expression pattern is taken as an indication of a putative regulatory link. Putative regulatory links are then aggregated over all genes to provide a ranking of interactions from which the whole network is reconstructed. In addition to performing well on the DREAM4 In Silico Multifactorial challenge simulated data, we show that GENIE3 compares favorably with existing algorithms to decipher the genetic regulatory network of Escherichia coli. It doesn't make any assumption about the nature of gene regulation, can deal with combinatorial and non-linear interactions, produces directed GRNs, and is fast and scalable. In conclusion, we propose a new algorithm for GRN inference that performs well on both synthetic and real gene expression data. The algorithm, based on feature selection with tree-based ensemble methods, is simple and generic, making it adaptable to other types of genomic data and interactions.

Hybrid incompatibility arises in a sequence-based bioenergetic model of transcription factor binding.

Science.gov (United States)

Tulchinsky, Alexander Y; Johnson, Norman A; Watt, Ward B; Porter, Adam H

2014-11-01

Postzygotic isolation between incipient species results from the accumulation of incompatibilities that arise as a consequence of genetic divergence. When phenotypes are determined by regulatory interactions, hybrid incompatibility can evolve even as a consequence of parallel adaptation in parental populations because interacting genes can produce the same phenotype through incompatible allelic combinations. We explore the evolutionary conditions that promote and constrain hybrid incompatibility in regulatory networks using a bioenergetic model (combining thermodynamics and kinetics) of transcriptional regulation, considering the bioenergetic basis of molecular interactions between transcription factors (TFs) and their binding sites. The bioenergetic parameters consider the free energy of formation of the bond between the TF and its binding site and the availability of TFs in the intracellular environment. Together these determine fractional occupancy of the TF on the promoter site, the degree of subsequent gene expression and in diploids, and the degree of dominance among allelic interactions. This results in a sigmoid genotype-phenotype map and fitness landscape, with the details of the shape determining the degree of bioenergetic evolutionary constraint on hybrid incompatibility. Using individual-based simulations, we subjected two allopatric populations to parallel directional or stabilizing selection. Misregulation of hybrid gene expression occurred under either type of selection, although it evolved faster under directional selection. Under directional selection, the extent of hybrid incompatibility increased with the slope of the genotype-phenotype map near the derived parental expression level. Under stabilizing selection, hybrid incompatibility arose from compensatory mutations and was greater when the bioenergetic properties of the interaction caused the space of nearly neutral genotypes around the stable expression level to be wide. F2's showed higher

A qualitative exploration of the major challenges facing pharmacovigilance in Saudi Arabia.

Science.gov (United States)

Aljadhey, Hisham; Mahmoud, Mansour A; Alshammari, Thamir M; Al-Dhaeefi, Mohammed; Le Louet, Herve; Perez-Gutthann, Susana; Pitts, Peter J

2015-09-01

To explore the challenges facing pharmacovigilance in Saudi Arabia and formulate recommendations to improve it from the perspective of healthcare professionals in Saudi Arabia. This was a qualitative study of 4 focus group discussions with pharmacists, physicians, and academicians held under the auspices of the King Saud University School of Pharmacy and the Center for Medicine in the Public Interest, Riyadh, Saudi Arabia. A total of 29 eligible healthcare professionals were invited to participate in the discussion. The predefined themes of the study were the current practice and major challenges facing pharmacovigilance in regulatory bodies, hospitals, the community, and academia, as well as recommendations to improve pharmacovigilance practice.  Of the 29 participants invited, 27 attended the discussion. Challenges facing regulatory bodies included complicated adverse drug reactions (ADR) reporting forms, lack of feedback on ADRs submitted to the Saudi Food and Drug Authority, lack of decisions from the local authority to withdraw medications, and lack of data on pharmacovigilance. The challenges to pharmacovigilance in hospitals included the lack of knowledge of the significance of ADR reporting, workload, blaming culture, and lack of collaboration between regulatory bodies and hospitals. However, challenges facing pharmaceutical industries included the lack of drug manufacturers in Saudi Arabia and lack of interest in pharmacovigilance. Recommendations to improve pharmacovigilance included the need for communication, stronger regulatory requirements, the need for research, the need for unified ADRs reporting, and continuous education and training.  The study has identified the challenges facing pharmacovigilance in Saudi Arabia and made certain recommendations to overcome them. These recommendations might be helpful for regulatory bodies to enhance spontaneous reporting and promote pharmacovigilance.

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

Science.gov (United States)

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

2018-01-01

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

A 3D bioprinting exemplar of the consequences of the regulatory requirements on customized processes.

Science.gov (United States)

Hourd, Paul; Medcalf, Nicholas; Segal, Joel; Williams, David J

2015-01-01

Computer-aided 3D printing approaches to the industrial production of customized 3D functional living constructs for restoration of tissue and organ function face significant regulatory challenges. Using the manufacture of a customized, 3D-bioprinted nasal implant as a well-informed but hypothetical exemplar, we examine how these products might be regulated. Existing EU and USA regulatory frameworks do not account for the differences between 3D printing and conventional manufacturing methods or the ability to create individual customized products using mechanized rather than craft approaches. Already subject to extensive regulatory control, issues related to control of the computer-aided design to manufacture process and the associated software system chain present additional scientific and regulatory challenges for manufacturers of these complex 3D-bioprinted advanced combination products.

Continuous Improvement of the Regulatory Framework for the Control of Medical Exposure

International Nuclear Information System (INIS)

Larcher, A.M.; Ortiz lopez, Pedro; Arias, Cesar; Marechal, Maria H.; Hernandez Alvarez, Ramon; Ferrer Garcia, Natividad; Castaneda Mucino, Antonia; Faller, Blanca

2011-01-01

Background: One of the key elements to guide the improvement of the regulatory control is the availability of a self-assessment tool for regulatory performance. Although there is general guidance on self-assessment for regulators and users (IAEA), there is a need for specific advice on how to address challenges and difficulties faced by regulatory bodies, when regulating radiation protection of patients. Examples of these challenges are the need of regulatory initiatives, in cooperation with health and education authorities, professional bodies and equipment suppliers, and to put in place necessary elements that are beyond responsibility of individual users of radiation, to enable them compliance with safety standards. Purpose: within the programme of the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations, a project to develop such a self assessment tool for the regulatory control of medical exposure has been designed. Method: national experiences in transposing and enforcing the international radiation safety standards, as to how the requirements are included in national regulations are reviewed. Further, difficulties to the implementation of safety requirements are included in national regulations are analyzed and a self assessment approach and possible regulatory solutions are presented. Results and discussion: in tis study the following documents are being produced: 1) Transposition of international requirements into national regulations in the six countries of the Forum, 2) difficulties to implement and enforce the requirements, 3) guidance on self assessment of regulatory framework for medical exposure, 4) suggested contribution to the revision of international radiation safety standards. (authors)

The regulatory and waste safety infrastructure of Bangladesh: Present status and future direction

International Nuclear Information System (INIS)

Kazi, O.A.

2001-01-01

Although nuclear energy and ionizing radiation exist as this planet earth exists, the history of human use of these energies is only a little over hundred years old. Nuclear and radiological practices are of immense benefit to society. But, like all other practices, nuclear and radiological practices also involve risks of a special type and nature. People and media are particularly sensitive to the use as well as to any accident or emergency involving the practices. Necessary laws and regulatory bodies have existed in many countries for a long time to control and keep the risks within acceptable limits. Nonetheless, accidents do occur and emergencies arise, which leads to the questioning of such regulatory systems' effectiveness. International interaction and co-operation are essential to addressing societal concerns appropriately. Bangladesh, though late, has also enacted laws and established a regulatory system to control the practices. This paper focuses on the country's regulatory status, hurdles being faced in implementing the legal requirements, and future thinking to increase effectiveness and efficiency. (author)

The Challenges of Digital Leadership

Science.gov (United States)

McLeod, Scott

2015-01-01

Because digital devices and online environments can simultaneously be transformatively empowering and maddeningly disruptive, the work of integrating digital learning tools into schools is usually difficult and complex. Common challenges arise, however, and can be thoughtfully addressed by proactive leadership. In the end, technology change in…

Guidance notes for the protection of persons against ionising radiations arising from medical and dental use

International Nuclear Information System (INIS)

1988-01-01

Guidance notes have been prepared by the NRPB, the Health Departments and the Health and Safety Executive for the protection of all persons against ionising radiations arising from medical and dental use. The guidance notes are a guide to good radiation protection practice consistent with regulatory requirements. The areas covered include medical and dental radiology, diagnostic X-ray equipment for medical and dental radiography, beam therapy and remotely controlled after-loading, brachytherapy, diagnostic and therapeutic uses of unsealed radioactive substances, diagnostic uses of sealed or other solid radioactive sources, patients leaving hospital after administration of radioactive substances, precautions after death of a patient whom radioactive substances have been administered, storage and movement of radioactive substances, disposal of radioactive waste and contingency planning and emergency procedures. (U.K.)

Primary extradural meningioma arising from the calvarium | Ravi ...

African Journals Online (AJOL)

Meningiomas are the most common intracranial tumours. Meningiomas arising at other locations are termed primary extradural meningiomas (EDMs) and are rare. Here we report a case of EDM arising from the calvarium – a primary calvarial meningioma (PCM).

Challenges in Regulating Radiation Sources and Associated Waste Management

International Nuclear Information System (INIS)

Shehzad, A.

2016-01-01

Radiation sources are widely used in the fields of medical, industry, agriculture, research, etc. Owing to the inherent risk of exposure to ionizing radiations while using the radiation sources and management of associated waste, safety measures are of utmost importance including robust regulatory control. Pakistan Nuclear Regulatory Authority (PNRA) is responsible for supervising all matters pertaining to nuclear safety and radiation protection in the country. Since its inception, PNRA has made rigorous efforts to regulate the radiation facilities for which regulatory framework was further strengthened by taking into account international norms/practices and implemented afterwards. However, due to vibrant use of these facilities, there are numerous challenges being faced while implementing the regulatory framework. These challenges pertains to shielding design of some facilities, control over service provider for QC/repair maintenance of radiation equipment, assessment of patient doses, and establishment of national diagnostic reference levels for radiological procedures. Further, the regulatory framework also delineate requirements to minimize the generation of associated radioactive waste as low as practicable. The requirements also necessitates that certain sealed radioactive sources (SRS) are returned to the supplier upon completion of their useful life, while other radioactive sources are required to be transported for storage at designated radioactive waste storage facilities in the country, which requires commitment from the licensee. This paper will briefly describe the challenges in regulating the radiation sources and issues related to the waste management associated with these facilities. (author)

ITER safety challenges and opportunities

International Nuclear Information System (INIS)

Piet, S.J.

1992-01-01

This paper reports on results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ITER is capable of meeting anticipated regulatory dose limits, but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. Much research and development (R ampersand D) and design analysis is needed to establish that ITER meets regulatory requirements. There is a further oportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, three programmatic challenges and three technical challenges must be overcome. The first step is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of three key technical challenges is plasma engineering - burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost

Crisis Communication of Nuclear Regulatory Organisations: Towards global thinking

International Nuclear Information System (INIS)

Martell, Meritxell; Menendez, Susan; Calvo, Marina

2013-01-01

The OECD Nuclear Energy Agency (NEA) Committee on Nuclear Regulatory Activities (CNRA) Working Group on Public Communication of Nuclear Regulatory Organisations (WGPC) organised the workshop 'Crisis communication: facing the challenges' on 9-10 May 2012 in Madrid to address the international dimension of the communicative responses to crises by assessing the experience of Nuclear Regulatory Organisations of the NEA member countries and their stakeholders. The CNRA/WGPC also prepared in 2011, before the Fukushima-Daiichi nuclear accident occurred, a Road Map for Crisis Communication of Nuclear Regulatory Organisations which focused only on national aspects. This 'road map' had not considered the international dimension. CNRA mandated the WGPC to expand the Road Map so as to conclude the follow-up activity on crisis communication. The objective of the present document is to firstly, identify the key messages which can be extracted from three surveys carried out among the WGPC members after Fukushima-Daiichi's accident (Appendices II, III and IV), and incorporate them into the Road Map for Crisis Communication. Secondly, the good practices on public communication of NROs, which were presented during the OECD/NEA Workshop on Crisis Communication: Facing the Challenges, are reported. Following the structure of the road map for public communication responses during crisis included in the NEA report entitled 'Road Map for Crisis Communication of Nuclear Regulatory Organisations - National aspects', the good practices on communication before, during and after a crisis are provided. Overall, the emphasis of this report is on the international aspects of crisis communication, rather than the national dimension. (authors)

Does nanobiotechnology oversight present a uniquely complex challenge to interagency cooperation?

International Nuclear Information System (INIS)

Karkkainen, Bradley C.

2011-01-01

Numerous regulatory and oversight challenges exist in the field of nanobiotechnology. Although these challenges may appear novel and complex, similar issues have plagued environmental regulation since the 1970 s. This article argues that complexity, uncertainty, and regulatory gaps are common problems in environmental regulation, and that the lessons learned and progress made during more than 40 years of environmental regulation can serve as a guidepost for addressing nanobiotechnology regulation and oversight issues.

Translational and Regulatory Challenges for Exon Skipping Therapies

NARCIS (Netherlands)

Aartsma-Rus, Annemieke; Ferlini, Alessandra; Goemans, Nathalie; Pasmooij, Anna M. G.; Wells, Dominic J.; Bushby, Katerine; Vroom, Elizabeth; Balabanov, Pavel

2014-01-01

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and

Current status of developmental neurotoxicity: regulatory view

DEFF Research Database (Denmark)

Hass, Ulla

2003-01-01

in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US....... Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...

Barcoded DNA-tag reporters for multiplex cis-regulatory analysis.

Directory of Open Access Journals (Sweden)

Jongmin Nam

Full Text Available Cis-regulatory DNA sequences causally mediate patterns of gene expression, but efficient experimental analysis of these control systems has remained challenging. Here we develop a new version of "barcoded" DNA-tag reporters, "Nanotags" that permit simultaneous quantitative analysis of up to 130 distinct cis-regulatory modules (CRMs. The activities of these reporters are measured in single experiments by the NanoString RNA counting method and other quantitative procedures. We demonstrate the efficiency of the Nanotag method by simultaneously measuring hourly temporal activities of 126 CRMs from 46 genes in the developing sea urchin embryo, otherwise a virtually impossible task. Nanotags are also used in gene perturbation experiments to reveal cis-regulatory responses of many CRMs at once. Nanotag methodology can be applied to many research areas, ranging from gene regulatory networks to functional and evolutionary genomics.

Regulatory control analysis and design for sewer systems

DEFF Research Database (Denmark)

Mollerup, Ane Loft; Mikkelsen, Peter Steen; Thornberg, Dines

2015-01-01

A systematic methodology for regulatory control analysis and design is adapted for sewer system operation and evaluated. The main challenge with adapting the methodology is the handling of the stochastic and transient nature of the rainfall disturbances, inherent to sewer system operation...

Cryptocurrencies & the Challenge of Global Governance

Directory of Open Access Journals (Sweden)

Garry Jacbs

2018-05-01

Full Text Available The recent explosive development of new forms of digital currency opens up unprecedented opportunities and poses significant regulatory challenges. This new form of digital currency lowers the costs and other barriers to the global movement of money, international trade, foreign investment and speculation, while simultaneously enhancing the anonymity on which tax evasion, money-laundering and other illegal activities thrive. It also liberates the creation of money and regulation of economic activities from the political control of national governments and central banks. Since the value of a currency is related to the size of the population, strength of the economy and value of transactions that utilize it, a basket of cryptocurrencies could emerge as the first prototype of a world currency whose value is backed by the total productive capacity of the entire human community. Moreover, the triad of Internet, distributed ledger technologies and cryptocurrencies could serve as the basis for the development of new global economic potentials in a manner similar and a degree far exceeding the economic impact of the World Wide Web over the past two decades. At the same time, the rapid deployment of cryptocurrencies could have profound impact on the capacity of governments to tax transactions, income and wealth, one of the main pillars of the modern nation state. The development of autonomous global cryptocurrencies could dramatically reduce the control and effectiveness of existing regulatory mechanisms at the national level and generate considerable pressure for the evolution of more effective institutions for global governance. They could provide compelling incentives for national governments to enhance international cooperation and strengthen the functioning of international institutions to fill the regulatory void. International organizations will play an important role in harnessing the potentials and minimizing the risks arising from the growing

The African Health Profession Regulatory Collaborative for Nurses and Midwives

Directory of Open Access Journals (Sweden)

McCarthy Carey F

2012-08-01

Full Text Available Abstract Background More than thirty-five sub-Saharan African countries have severe health workforce shortages. Many also struggle with a mismatch between the knowledge and competencies of health professionals and the needs of the populations they serve. Addressing these workforce challenges requires collaboration among health and education stakeholders and reform of health worker regulations. Health professional regulatory bodies, such as nursing and midwifery councils, have the mandate to reform regulations yet often do not have the resources or expertise to do so. In 2011, the United States of America Centers for Disease Control and Prevention began a four-year initiative to increase the collaboration among national stakeholders and help strengthen the capacity of health professional regulatory bodies to reform national regulatory frameworks. The initiative is called the African Health Regulatory Collaborative for Nurses and Midwives. This article describes the African Health Regulatory Collaborative for Nurses and Midwives and discusses its importance in implementing and sustaining national, regional, and global workforce initiatives. Discussion The African Health Profession Regulatory Collaborative for Nurses and Midwives convenes leaders responsible for regulation from 14 countries in East, Central and Southern Africa. It provides a high profile, south-to-south collaboration to assist countries in implementing joint approaches to problems affecting the health workforce. Implemented in partnership with Emory University, the Commonwealth Secretariat, and the East, Central and Southern African College of Nursing, this initiative also supports four to five countries per year in implementing locally-designed regulation improvement projects. Over time, the African Health Regulatory Collaborative for Nurses and Midwives will help to increase the regulatory capacity of health professional organizations and ultimately improve regulation and

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

Science.gov (United States)

Kramer, Gregory M; Luxton, David D

2016-04-01

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

Future consequences and challenges for dairy cow production systems arising from climate change in Central Europe - a review.

Science.gov (United States)

Gauly, M; Bollwein, H; Breves, G; Brügemann, K; Dänicke, S; Daş, G; Demeler, J; Hansen, H; Isselstein, J; König, S; Lohölter, M; Martinsohn, M; Meyer, U; Potthoff, M; Sanker, C; Schröder, B; Wrage, N; Meibaum, B; von Samson-Himmelstjerna, G; Stinshoff, H; Wrenzycki, C

2013-05-01

It is well documented that global warming is unequivocal. Dairy production systems are considered as important sources of greenhouse gas emissions; however, little is known about the sensitivity and vulnerability of these production systems themselves to climate warming. This review brings different aspects of dairy cow production in Central Europe into focus, with a holistic approach to emphasize potential future consequences and challenges arising from climate change. With the current understanding of the effects of climate change, it is expected that yield of forage per hectare will be influenced positively, whereas quality will mainly depend on water availability and soil characteristics. Thus, the botanical composition of future grassland should include species that are able to withstand the changing conditions (e.g. lucerne and bird's foot trefoil). Changes in nutrient concentration of forage plants, elevated heat loads and altered feeding patterns of animals may influence rumen physiology. Several promising nutritional strategies are available to lower potential negative impacts of climate change on dairy cow nutrition and performance. Adjustment of feeding and drinking regimes, diet composition and additive supplementation can contribute to the maintenance of adequate dairy cow nutrition and performance. Provision of adequate shade and cooling will reduce the direct effects of heat stress. As estimated genetic parameters are promising, heat stress tolerance as a functional trait may be included into breeding programmes. Indirect effects of global warming on the health and welfare of animals seem to be more complicated and thus are less predictable. As the epidemiology of certain gastrointestinal nematodes and liver fluke is favourably influenced by increased temperature and humidity, relations between climate change and disease dynamics should be followed closely. Under current conditions, climate change associated economic impacts are estimated to be

NTL 11 spent fuel flask - meeting the challenge of regulatory and technological change

International Nuclear Information System (INIS)

Cory, A.R.

2004-01-01

By June 2005, when shipments of spent fuel for reprocessing from Germany are concluded, the NTL11 flask type will have been responsible for transporting a total of 1500 tonnes of heavy metal in the form of spent fuel. Excluding domestic transports in France and the UK, this represents 25% of the total European spent fuel transported for reprocessing since the flasks came into service in 1977. Approximately 40% of the total for the flask type will have been transported to BNFL's Sellafield facility, the remainder to Cogema at La Hague. The NTL11 flask can justifiably be described as being the workhorse of BNFL's European spent fuel transport business. The NTL11 flask started life under the ownership of Nuclear Transport Limited, an associate company of BNFL, and in recent years the original fleet of five flasks has been absorbed into the BNFL inventory. A recent build programme has seen a further four flasks added to the fleet, an expedient measure to cope with the additional transport requirements imposed by the need to meet the June 2005 deadline for the removal of contracted fuels from Germany. While there have been certain evolutionary changes affecting the package design, there have also been more significant changes in the Design Safety Case. These have sometimes been necessary to meet regulatory changes, or the challenges posed by the regulators. In other cases advantage has been taken of improvements in analytical techniques to demonstrate increased margins of operational safety. Where possible those margins have also been increased by other means, such as taking advantage of commercial trends to reduce package thermal loads. The NTL11 flask was designed around the reactor and fuel characteristics prevailing in the 1970's. Over the lifetime of the flask the responsible engineering teams have faced and met the successive challenges to develop the capability of the Package to face the changing requirements of the industry and the Transport Regulations. Both

Human-Interaction Challenges in UAV-Based Autonomous Surveillance

Science.gov (United States)

Freed, Michael; Harris, Robert; Shafto, Michael G.

2004-01-01

Autonomous UAVs provide a platform for intelligent surveillance in application domains ranging from security and military operations to scientific information gathering and land management. Surveillance tasks are often long duration, requiring that any approach be adaptive to changes in the environment or user needs. We describe a decision- theoretic model of surveillance, appropriate for use on our autonomous helicopter, that provides a basis for optimizing the value of information returned by the UAV. From this approach arise a range of challenges in making this framework practical for use by human operators lacking specialized knowledge of autonomy and mathematics. This paper describes our platform and approach, then describes human-interaction challenges arising from this approach that we have identified and begun to address.

A safe transoral surgical approach to parapharyngeal tumor arising from deep lobe of parotid gland

Directory of Open Access Journals (Sweden)

Manuele Casale

2016-12-01

Full Text Available The management of parapharyngeal tumor is surgical, but the approach remains a challenge. Attention should be paid to avoidance intra-operative bleeding or cranial nerves damage. We report a case of a 67-year-old male complaining of left-ear fullness. A submucosal mass arising from the lateral wall of oropharynx on the left side was observed. Magnetic resonance imaging detected a mass arising from the parotid gland, in particular from the deep lobe, and a fine needle biopsy was compatible with “Warthin tumor.” We performed a mini-invasive transoral approach under magnification, previous isolation of homolateral vessels. The decision on which surgical approach to be used is determined by site, size vascularity, and histology of the tumor. A literature review of the main surgical approaches was performed. We performed a combined transoral dissection under magnification with cervicotomic exposure of the neck vascular bundle allowing to dissect the tumor and manage any intra-operative complications.

Semi-supervised prediction of gene regulatory networks using ...

Indian Academy of Sciences (India)

2015-09-28

Sep 28, 2015 ... Use of computational methods to predict gene regulatory networks (GRNs) from gene expression data is a challenging ... two types of methods differ primarily based on whether ..... negligible, allowing us to draw the qualitative conclusions .... research will be conducted to develop additional biologically.

Breeding and regulatory opportunities and constraints for developing broccoli cultivars adapted to organic agriculture

NARCIS (Netherlands)

Renaud, E.N.C.

2014-01-01

This thesis is about the regulatory and technical challenges to the organic seed and breeding sector. This study specifically explored the mutual influence of the regulatory environment for organic seed sector development in the United States (US), Europe Union (EU) and Mexico, and the extent to

Regulatory adequacy of aquatic ecotoxicity testing of nanomaterials

DEFF Research Database (Denmark)

Hjorth, Rune; Skjolding, Lars Michael; Sørensen, Sara Nørgaard

2017-01-01

between studies, which question the regulatory reliability of the data currently available. Accordingly, lack of data suited for regulatory decision-making is still a pressing issue in nanoecotoxicology even though the data availability has increased. Nevertheless, we emphasize that by deliberately...... to question whether ecotoxicity testing is now able to facilitate regulatory decision-making on manufactured nanomaterials (MNs). In this paper, we review the state of aquatic ecotoxicity testing of MNs as well as the overarching issues that challenge the reliability and relevance of such testing. We conclude...... that within the field there is an increased focus on characterization of the exposure rather than controlling exposure as it is traditionally done in guideline testing of chemicals. However, the lack of characterization options under actual testing conditions makes it difficult to make meaningful comparisons...

The Regulatory Framework for Privacy and Security

Science.gov (United States)

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.

Understanding how to maintain compliance in the current regulatory climate

International Nuclear Information System (INIS)

Bignell, D.T.; Burns, R.

1995-01-01

High level radioactive waste facilities must maintain compliance with all regulatory requirements, even those requirements that have been promulgated after the facility was placed into operation. Facilities must aggressively pursue compliance because environmental laws often impose strict liability for violations; therefore, an honest mistake is no defense. Radioactive waste management is constantly under the public microscope, particularly those facilities that handle high-level radioactive waste. The Savannah River Site has effectively met the challenges of regulatory compliance in its HLRW facilities and plans are being formulated to meet future regulatory requirements as well. Understanding, aggressively achieving, and clearly demonstrating compliance is essential for the continued operations of radioactive waste management facilities. This paper examines how HLRW facilities are impacted by regulatory requirements and how compliance in this difficult area is achieved and maintained

Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

Science.gov (United States)

Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

2017-10-01

During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

The challenges for human factors in knowledge work

DEFF Research Database (Denmark)

Ipsen, Christine; Møller, Niels; Jensen, Per Langaa

2011-01-01

The development towards a service and knowledge intensive economy arise new challenges for ergonomics and human factors. Knowledge on work within mass service production exists, but the challenges within knowledge work have still to be addressed. The focus of this paper is on some of the challeng...... with the demands of the knowledge intensive work when KPI’s are central management tools. Especially handling the balance between high motivation and enthusiasm and burn out will be addressed....

Using Inequality Measures to Incorporate Environmental Justice into Regulatory Analyses

Science.gov (United States)

Harper, Sam; Ruder, Eric; Roman, Henry A.; Geggel, Amelia; Nweke, Onyemaechi; Payne-Sturges, Devon; Levy, Jonathan I.

2013-01-01

Formally evaluating how specific policy measures influence environmental justice is challenging, especially in the context of regulatory analyses in which quantitative comparisons are the norm. However, there is a large literature on developing and applying quantitative measures of health inequality in other settings, and these measures may be applicable to environmental regulatory analyses. In this paper, we provide information to assist policy decision makers in determining the viability of using measures of health inequality in the context of environmental regulatory analyses. We conclude that quantification of the distribution of inequalities in health outcomes across social groups of concern, considering both within-group and between-group comparisons, would be consistent with both the structure of regulatory analysis and the core definition of environmental justice. Appropriate application of inequality indicators requires thorough characterization of the baseline distribution of exposures and risks, leveraging data generally available within regulatory analyses. Multiple inequality indicators may be applicable to regulatory analyses, and the choice among indicators should be based on explicit value judgments regarding the dimensions of environmental justice of greatest interest. PMID:23999551

Regulatory Models and the Environment: Practice, Pitfalls, and Prospects

Energy Technology Data Exchange (ETDEWEB)

Holmes, K. John; Graham, Judith A.; McKone, Thomas; Whipple, Chris

2008-06-01

Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties, because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the US Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside of the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. Evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the"life cycle" of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than for non-regulatory models.

Drug shortages in Israel: regulatory perspectives, challenges and solutions.

Science.gov (United States)

Schwartzberg, Eyal; Ainbinder, Denize; Vishkauzan, Alla; Gamzu, Ronni

2017-01-01

Pharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients' wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013-2015, assessing their etiology and exploring the steps taken for their mitigation and prevention. The database of the Israeli Ministry of Health (MoH) on drug shortages contains all the DSs recorded in Israel since 2013, detailing the cause of the DS, its duration, steps taken in its' management and the availability of generic or therapeutic alternatives. Selected examples of DSs from the database are described in this paper in order to identify the causes of DSs, the scope of the problem and possible solutions. Additionally, we have reviewed the recent activities performed by European Medicine Agency (EMA) and the American Food and Drug Administration (FDA) in their efforts to minimize this problem. Several factors contributing towards DSs in Israel were identified, including quality problems in both the final drug product and in the raw materials, upgrades and improvements of the manufacturing process required by the MoH, manufacturing by a sole supplier, dramatic price decrease in off-patent medications causing the manufacturer to discontinue the distribution of the product in Israel, just-in-time inventory control, and others. One of the most important steps in managing drug shortages was identified to be early notification of the shortage by the Marketing Authorization Holder (MAH) to the MoH. In 2013, the Israeli MoH updated the regulation on drug shortages instructing MAHs on their obligation of early notification to the MoH. Furthermore, various steps dealing with marketing withdrawal of drugs

The Safety Culture of an Effective Nuclear Regulatory Body

International Nuclear Information System (INIS)

Carlsson, Lennart; Bernard, Benoit; Lojk, Robert; Koskinen, Kaisa; Rigail, Anne-Cecile; Stoppa, Gisela; Lorand, Ferenc; Aoki, Masahiro; Fujita, Kenichi; Takada, Hiroko; Kurasaki, Takaaki; Choi, Young Sung; Smit, Martin; Bogdanova, Tatiana; Sapozhnikov, Alexander; Smetnik, Alexander; Cid Campo, Rafael; Axelsson, Lars; Carlsson, Lennart; Edland, Anne; Ryser, Cornelia; Cohen, Miriam; Ficks, Ben; Valentin, Andrea; Nicic, Adriana; Lorin, Aurelie; Nezuka, Takayoshi; Creswell, Len

2016-01-01

The fundamental objective of all nuclear safety regulatory bodies is to ensure that activities related to the peaceful use of nuclear energy are carried out in a safe manner within their respective countries. In order to effectively achieve this objective, the nuclear regulatory body requires specific characteristics, one of which is a healthy safety culture. This regulatory guidance report describes five principles that support the safety culture of an effective nuclear regulatory body. These principles concern leadership for safety, individual responsibility and accountability, co-operation and open communication, a holistic approach, and continuous improvement, learning and self-assessment. The report also addresses some of the challenges to a regulatory body's safety culture that must be recognised, understood and overcome. It provides a unique resource to countries with existing, mature regulators and can be used for benchmarking as well as for training and developing staff. It will also be useful for new entrant countries in the process of developing and maintaining an effective nuclear safety regulator. (authors)

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

Science.gov (United States)

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.

Opening Address [International Conference on Effective Nuclear Regulatory Systems: Further Enhancing the Global Nuclear Safety and Security Regime, Cape Town (South Africa), 14-18 December 2009

International Nuclear Information System (INIS)

Peters, Elizabeth Dipuo

2010-01-01

Nuclear energy is seen by many countries as providing a sustainable solution to energy security challenges. In this context, many developing countries are considering the establishment of nuclear power build programmes, while countries with mature nuclear programmes are considering the possibility of further expansion. The challenges facing countries that are embarking on this new venture include, inter alia, the development of policies, legislation as well as the establishment of appropriate institutions such as regulatory bodies with effective independence to take regulatory decisions. Regional and international cooperation and coordination are therefore of critical importance. Accordingly, the establishment of the Forum of Regulatory Bodies in Africa is a welcome initiative. We are pleased that the national nuclear programme in post-apartheid South Africa places us in a position to become active global participants in the safe use of nuclear energy for peaceful purposes. However, we all have an obligation to ensure that the presence of a plethora of cooperation mechanisms such as this body are as inclusive and as supportive as possible. This will help the global community of nations in reaping maximum benefits that surely should arise from these initiatives to ensure security of energy supply. We do not have the luxury to duplicate such bodies. The role of the International Atomic Energy Agency in nuclear safety and security cannot be over-emphasized. That alone is the reason that drove the liberation movement of the people of our country, and now the ruling party, fully to conform to all the treaties and conventions that have been drafted by this reputable institution of the peoples of the world. The same goes for the facilitation of cooperation and the sharing of knowledge and experience. The IAEA is invariably trusted to provide independent views and advice in order to strengthen safety and security while preserving the sovereignty, authority and

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

Science.gov (United States)

McKenna, Dennis J

2004-05-01

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

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

Science.gov (United States)

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.

Endogeneously arising network allocation rules

NARCIS (Netherlands)

Slikker, M.

2006-01-01

In this paper we study endogenously arising network allocation rules. We focus on three allocation rules: the Myerson value, the position value and the component-wise egalitarian solution. For any of these three rules we provide a characterization based on component efficiency and some balanced

French Regulatory Framework for the Recycling/Reuse of Nuclear Waste and the Dismantling of George Besse Gaseous Diffusion Plant

Energy Technology Data Exchange (ETDEWEB)

Themines, R., E-mail: robert.themines@areva.com [AREVA (France)

2011-07-15

The regulatory framework in France governing the management of materials containing low levels of radionuclides is described. The plans for the management of the materials arising from the dismantling of the Georges Besse Gaseous Diffusion Plant are described as an example of the application of the regulations. (author)

A systems level approach reveals new gene regulatory modules in the developing ear

OpenAIRE

Chen, Jingchen; Tambalo, Monica; Barembaum, Meyer; Ranganathan, Ramya; Simões-Costa, Marcos; Bronner, Marianne E.; Streit, Andrea

2017-01-01

The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition ...

Deployment of SIP in MANET: challenges and circumvention

Directory of Open Access Journals (Sweden)

Abdelhamid Salma R.

2017-01-01

Full Text Available The immense growth in wireless network applications has encouraged the researchers to enhance and propose new approaches that facilitate the deployment of the widely used services, protocols, and applications of the wired networking area in the wireless networks. Among which, the Session Initiation Protocol (SIP is a signaling protocol that allows the establishment of multimedia sessions and calls between different parties. SIP functionality totally depends on a centralized infrastructure, and complexity arises when deploying such a protocol in a special type of wireless networks, namely Mobile Ad-hoc Networks (MANET, due to the absence of a centralized infrastructure, and the dynamic topology of the later. This paper highlights the the challenges arising when deploying SIP in MANETs and presents an overview of different proposed approaches to overcome these challenges.

Evaluation of NORM in facility Venezuelan oil industry to establish regulatory criteria; Evaluacion de NORM en una instalacion de la industria petrolera venezolana para establecer los criterios reguladores

Energy Technology Data Exchange (ETDEWEB)

Acevedo Lozada, D. J.; Rivas, I.; Davila, L.; Flores, Y.

2013-07-01

The present work shows the need to identify, in the Venezuelan oil industry, the existence of exposure to natural sources of radiation should be considered as occupational. As Regulatory Authority in the area of ionizing radiation the need for regulatory processes and ensure radiation protection of personnel involved in these practices arises, as well as personal and environmental monitoring. NORM identifying an installation of the Venezuelan oil industry to establish regulatory processes and take steps to ensure occupational radiation protection. (Author)

Carcinoma arising in thyroglossal remnants

NARCIS (Netherlands)

van Vuuren, P. A.; Balm, A. J.; Gregor, R. T.; Hilgers, F. J.; Loftus, B. M.; Delprat, C. C.; Rutgers, E. J.

1994-01-01

Three patients with a papillary carcinoma arising in a thyroglossal duct cyst are presented and the literature is reviewed. This rare malignancy is seen mostly in women between the ages of 20 and 50 years. The distribution of carcinoma subtypes differs from that of thyroid carcinomas and

The global conduct of cancer clinical trials: challenges and opportunities.

Science.gov (United States)

Barrios, Carlos H; Werutsky, Gustavo; Martinez-Mesa, Jeovany

2015-01-01

The nature of clinical research has changed substantially over the last 2 decades, evolving from being centered almost exclusively in developed countries to a more global scenario that is increasingly involving less developed regions of the world. Pharmaceutical companies and some academic cooperative groups have been conducting challenging, large pivotal registration studies with multinational participation. The much more needed globalization of academic research demands particular attention and represents a worthwhile subject for a more profound discussion. The requirement of large sample sizes and the potential for fast recruitment leading to a speedy completion of clinical studies are probably the most important factors that have fueled globalization of studies. Reduced operational costs and the ability to expedite the regulatory approval of drugs in various countries or regions are also important drivers. Globalization of research should be seen as having a much wider effect in the societies involved, in particular, when we consider public health, economic, social, and ethical implications. Most importantly, the process of expanding the network of clinical research sites also fosters the integration and the development of closer relationships among investigators at a global level. We consider this an essential element that should remain a prominent element in the discussion. In this article, we address the underlying reasons for globalization and we highlight some of the scientific and ethical concerns arising as a consequence. Finally, some strategies to address and mitigate the challenges of conducting multinational clinical research are proposed.

Precision genome engineering and agriculture: opportunities and regulatory challenges.

Science.gov (United States)

Voytas, Daniel F; Gao, Caixia

2014-06-01

Plant agriculture is poised at a technological inflection point. Recent advances in genome engineering make it possible to precisely alter DNA sequences in living cells, providing unprecedented control over a plant's genetic material. Potential future crops derived through genome engineering include those that better withstand pests, that have enhanced nutritional value, and that are able to grow on marginal lands. In many instances, crops with such traits will be created by altering only a few nucleotides among the billions that comprise plant genomes. As such, and with the appropriate regulatory structures in place, crops created through genome engineering might prove to be more acceptable to the public than plants that carry foreign DNA in their genomes. Public perception and the performance of the engineered crop varieties will determine the extent to which this powerful technology contributes towards securing the world's food supply.

Using Inequality Measures to Incorporate Environmental Justice into Regulatory Analyses

Science.gov (United States)

Abstract: Formally evaluating how specific policy measures influence environmental justice is challenging, especially in the context of regulatory analyses in which quantitative comparisons are the norm. However, there is a large literature on developing and applying quantitative...

Emotion: The Self-regulatory Sense.

Science.gov (United States)

Peil, Katherine T

2014-03-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system-perhaps the first sensory system to have emerged, serving the ancient autopoietic function of "self-regulation." Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of "self-relevant" sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes-evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health.

Emotion: The Self-regulatory Sense

Science.gov (United States)

2014-01-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system—perhaps the first sensory system to have emerged, serving the ancient autopoietic function of “self-regulation.” Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of “self-relevant” sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes—evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health. PMID:24808986

Adenosarcoma arising in hepatic endometriosis

International Nuclear Information System (INIS)

N'Senda, P.; Dahan, H.; Tubiana, J.M.; Arrive, L.; Wendum, D.; Balladur, P.

2000-01-01

We report a case of adenosarcoma arising in hepatic endometriosis. Both CT and MR scans demontrated a huge heterogeneous mass containing septated, thick-walled cystic lesions. After enlarged right hepatectomy, the patient was asymptomatic with no abnormalities at liver and abdominal CT scan at 2-year follow-up. (orig.)

Adenosarcoma arising in hepatic endometriosis

Energy Technology Data Exchange (ETDEWEB)

N' Senda, P.; Dahan, H.; Tubiana, J.M.; Arrive, L. [Service de Radiologie, Hopital Saint-Antoine, 75 - Paris (France); Wendum, D. [Service d' Anatomie Pathologie, Hopital Saint-Antoine, 75 - Paris (France); Balladur, P. [Service de Chirurgie Digestive et Generale, Hopital Saint-Antoine, 75 - Paris (France)

2000-08-01

We report a case of adenosarcoma arising in hepatic endometriosis. Both CT and MR scans demontrated a huge heterogeneous mass containing septated, thick-walled cystic lesions. After enlarged right hepatectomy, the patient was asymptomatic with no abnormalities at liver and abdominal CT scan at 2-year follow-up. (orig.)

T regulatory cells and related immunoregulatory factors in polymorphic light eruption following ultraviolet A1 challenge.

Science.gov (United States)

Gambichler, T; Terras, S; Kampilafkos, P; Kreuter, A; Skrygan, M

2013-12-01

Polymorphic light eruption (PLE) is considered to be an autoimmune-mediated skin condition in which the normal ultraviolet (UV)-induced local immunosuppression appears to be absent, leading to recognition of photoinduced autoantigens and subsequent inflammation. To investigate T regulatory cells (Tregs) and related immunoregulatory factors in PLE lesions and controls. Skin biopsies were performed in 13 patients with UVA1-challenged PLE, 12 female patients with chronic discoid lupus erythematosus (CDLE) and 11 healthy controls who had exposure to UVA1. Immunohistochemistry and four-colour immunofluorescence studies were performed. Patients with CDLE and UVA1-exposed controls showed significantly decreased epidermal immunoreactivity for CD1a compared with patients with PLE (P = 0·0001). Four-colour immunofluorescence revealed a median percentage of CD4+CD25+FOXP3+ Tregs of 7·6% (range 3·7-13·6%) in PLE, a median of 11·7% (range 9·5-13·9%) in CDLE and a median of 3·4% (range 0-6·8%) in controls. Compared with UVA1-exposed controls, PLE and CDLE lesions showed significantly decreased transforming growth factor (TGF)-β1 immunoreactivity in the epidermis (P = 0·0003). In PLE lesions, we observed significantly decreased interleukin (IL)-10 expression compared with CDLE (P = 0·022). In the dermis, receptor activator of nuclear factor-κB ligand (RANKL) expression was increased in UVA1-exposed controls compared with PLE and CDLE (P = 0·018). Similar to CDLE lesions, UVA1-challenged PLE lesions display an altered immunoregulatory network, as indicated by decreased epidermal or dermal expression of TGF-β1, IL-10 and RANKL, and a relatively low number of Tregs, particularly when compared with other inflammatory skin conditions reported in the literature. © 2013 British Association of Dermatologists.

ITER safety challenges and opportunities

International Nuclear Information System (INIS)

Piet, S.J.

1991-01-01

Results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ''ITER is capable of meeting anticipated regulatory dose limits,'' but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. We need much research and development (R ampersand D) and design analysis to establish that ITER meets regulatory requirements. We have a further opportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, we need to overcome three programmatic challenges and three technical challenges. The first programmatic challenge is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of the three key technical challenges is plasma engineering -- burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost. Some design requirements are now too strict; some are too lax. Fuel cycle design requirements are presently too strict, mandating inappropriate T separation from H and D. Heat sink requirements are presently too lax; they should be strengthened to ensure that maximum loss of coolant accident temperatures drop

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

Science.gov (United States)

Branson, Bernard M

2015-03-01

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

In silico discovery of transcription regulatory elements in Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Le Roch Karine G

2008-02-01

Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

U.S. Nuclear Regulatory Commission fiscal year 1980 supplemental budget request

International Nuclear Information System (INIS)

1979-01-01

The proposed supplemental will enable the Nuclear Regulatory Commission to implement necessary additional effort arising from the agency's assessment of the accident at the Three Mile Island Unit 2 facility on March 28, 1979. The TMI accident has had a major impact on all NRC program areas, in particular on research activities and reactor operations. In addition, funds are requested to enhance the agency's Waste Management program to reflect the recommendations of the President's Interagency Review Group on Waste Management. Specific activities involved in this effort will include developing regulatory guidance, developing a licensing review capability and completing a plan for the site characterization review, all in support of the preparation of NRC guidelines necessary to conduct a construction authorization review. FY 1980 appropriations did not include funds to cover these requirements. A detailed analysis across program lines of the supplemental request is contained in this report

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

Science.gov (United States)

Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Legal Challenges Related to the Regulation of a Domain Name System

Directory of Open Access Journals (Sweden)

Marius Kalinauskas

2012-12-01

Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system.Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies.Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field.Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis.Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models.Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes. The

Legal Challenges Related to the Regulation of a Domain Name System

Directory of Open Access Journals (Sweden)

Marius Kalinauskas

2013-02-01

Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system. Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies. Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field. Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis. Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models. Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes

Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

Science.gov (United States)

Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

2014-04-11

Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

Five challenges for public administrations in Europe

Directory of Open Access Journals (Sweden)

Ongaro Edoardo

2015-12-01

Full Text Available This article examines five ‘challenges’ facing most administrative systems across Europe. The first challenge stems from the increasingly asymmetric nature of European multilevel governance; the second challenge arises from the missed opportunity of reforming in the absence of a dominant administrative paradigm; the third challenge lies in rescuing and transforming the welfare state; the fourth challenge is concerned with making the most of the knowledge generated in the field of strategic management for strategically managing public services; the fifth challenge lies in staff (demotivation. These challenges are pitched at very different levels: some are related to issues of public governance, some to issues of scholarly and practitioners’ collective understandings of public administration in Europe, and some to trends in the global economy, and notably the financial, economic and fiscal ‘crises’.

Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

Science.gov (United States)

Bowman, Diana M; Gatof, Jake

2015-01-01

Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.

Challenges: a state and compact perspective

International Nuclear Information System (INIS)

Brown, H.

1987-01-01

The challenges facing states and compacts in their efforts to implement the Low-Level Waste Policy Amendments Act are described. Institutional challenges include: small-volume sites; compact maintenance; shifting agencies and changing personnel; and timing of progress. The technical challenge lies in the enormous number of plans, procedures, and regulations that have to be developed over the next four years. There are two main fiscal challenges: funding of day-to-day operations of compact commissions; and financing the siting and construction of new disposal sites. There are also two main regulatory challenges: host states must develop regulations for siting and selection of technology; and all states have to await federal regulations to be completed. The final challenge is political: whether a region can overcome public opposition and actually site a facility

Small finance banks: Challenges

Directory of Open Access Journals (Sweden)

Jayadev M

2017-12-01

Full Text Available A recent innovation in the Indian banking structure has been the formation of a new banking institution—small finance banks (SFBs. These banks are expected to penetrate into financial inclusion by providing basic banking and credit services with a differentiated banking model to the larger population. In this context the new SFBs have multiple challenges in coming out with a new, differentiated business model. The challenges include building low cost liability portfolio, technology management, and balancing the regulatory compliances. This paper also presents the top of mind views of three senior executives of new small finance banks.

Quenching rate for a nonlocal problem arising in the micro-electro mechanical system

Science.gov (United States)

Guo, Jong-Shenq; Hu, Bei

2018-03-01

In this paper, we study the quenching rate of the solution for a nonlocal parabolic problem which arises in the study of the micro-electro mechanical system. This question is equivalent to the stabilization of the solution to the transformed problem in self-similar variables. First, some a priori estimates are provided. In order to construct a Lyapunov function, due to the lack of time monotonicity property, we then derive some very useful and challenging estimates by a delicate analysis. Finally, with this Lyapunov function, we prove that the quenching rate is self-similar which is the same as the problem without the nonlocal term, except the constant limit depends on the solution itself.

Strengthening the regulatory control of consumer goods through international harmonization

International Nuclear Information System (INIS)

Yus Rusdian Akhmad

2013-01-01

The International Atomic Energy Agency (IAEA) is currently working on a recommendation in the form of guidelines for regulating consumer goods. Preparation of this document has a significant dimension of international issues, especially in terms of the application of the principles of justification and application of the concept of exemption. International harmonization among regulators ranging from the regional to the global level is a central issue and considering the complex issues that arise in addition to covering the scientific aspects also involve consideration of the legal aspects or values espoused by any State which may differ from one another. PERKA BAPETEN on consumer goods is still in the preparation stage so that the discussion of the material will be useful for improving the quality of the regulation in time. There is a significant gap of understanding to the related materials by the parties concerned (between local and international parties were among the local party). This paper intends to propose the understanding and views on radiation protection and regulatory control for consumer goods and hopely could contributed significantly to strengthening its regulatory control which is primarily through a reduction in the gap of understanding to the related concept that potentially multi perceptions and encourage stronger cooperation among regulatory bodies. (author)

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

Science.gov (United States)

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.

An Ethics Challenge for School Counselors

Science.gov (United States)

Froeschle, Janet G.; Crews, Charles

2010-01-01

Ethical issues arise more often for school counselors than for those who work in other settings (Remley, 2002). The challenge of working not only with minors but also with other stakeholders including parents, teachers, school administrators, and community members sets the stage for potential legal and ethical dilemmas. Awareness and adherence to…

Cutaneous osteosarcoma arising from a burn scar

Energy Technology Data Exchange (ETDEWEB)

Lee, Min A.; Yi, Jaehyuck [Kyungpook National University, Department of Radiology, College of Medicine, Daegu (Korea, Republic of); Kyungpook National University Hospital, Department of Radiology, Daegu (Korea, Republic of); Chae, Jong Min [Kyungpook National University, Department of Pathology, College of Medicine, Daegu (Korea, Republic of)

2017-04-15

Tumors that develop in old burn scars are usually squamous cell carcinomas. Sarcomas have also been reported, albeit rarely. To our knowledge, there has been only one case report of an extraskeletal osteosarcoma arising in a prior burn scar reported in the English-language literature, mainly discussing the clinicopathological features. Herein, we present a case of cutaneous osteosarcoma visualized as a mineralized soft-tissue mass arising from the scar associated with a previous skin burn over the back. This seems to be the first report describing the imaging features of a cutaneous osteosarcoma from an old burn scar. (orig.)

Validation and acceptability of double-blind, placebo-controlled food challenges in children

NARCIS (Netherlands)

Venter, Carina; Maslin, Kate; Patil, Veeresh; Grundy, Jane; Glasbey, Gillian; Raza, Abid; Vlieg-Boerstra, Berber; Dean, Taraneh

2016-01-01

The Double Blind Placebo Controlled Food Challenge (DBPCFC) is considered the gold standard for food allergy diagnosis (1, 2). It is recommended that active and placebo challenge foods for DBPCFCs are sufficiently blinded in terms of smell, flavour and texture. Difficulties arise with children

78 FR 67344 - American Energy Data Challenge

Science.gov (United States)

2013-11-12

... in cases of willful misconduct, for any injury, death, damage, or loss of personal property, revenue... Challenge competition, whether the injury, death, damage, or loss arises through negligence or otherwise. F... Government is without any warranty or representation whatsoever, including but not limited to its suitability...

Regulatory Safety Requirements for Operating Nuclear Installations

International Nuclear Information System (INIS)

Gubela, W.

2017-01-01

The National Nuclear Regulator (NNR) is established in terms of the National Nuclear Regulator Act (Act No 47 of 1999) and its mandate and authority are conferred through sections 5 and 7 of this Act, setting out the NNR's objectives and functions, which include exercising regulatory control over siting, design, construction etc of nuclear installations through the granting of nuclear authorisations. The NNR's responsibilities embrace all those actions aimed at providing the public with confidence and assurance that the risks arising from the production of nuclear energy remain within acceptable safety limits -> Therefore: Set fundamental safety standards, conducting pro-active safety assessments, determining licence conditions and obtaining assurance of compliance. The promotional aspects of nuclear activities in South Africa are legislated by the Nuclear Energy Act (Act No 46 of 1999). The NNR approach to regulations of nuclear safety and security take into consideration, amongst others, the potential hazards associated with the facility or activity, safety related programmes, the importance of the authorisation holder's safety related processes as well as the need to exercise regulatory control over the technical aspects such as of the design and operation of a nuclear facility in ensuring nuclear safety and security. South Africa does not have national nuclear industry codes and standards. The NNR is therefore non-prescriptive as it comes to the use of industry codes and standards. Regulatory framework (current) provide for the protection of persons, property, and environment against nuclear damage, through Licensing Process: Safety standards; Safety assessment; Authorisation and conditions of authorisation; Public participation process; Compliance assurance; Enforcement

Regulatory RNA-assisted genome engineering in microorganisms.

Science.gov (United States)

Si, Tong; HamediRad, Mohammad; Zhao, Huimin

2015-12-01

Regulatory RNAs are increasingly recognized and utilized as key modulators of gene expression in diverse organisms. Thanks to their modular and programmable nature, trans-acting regulatory RNAs are especially attractive in genome-scale applications. Here we discuss the recent examples in microbial genome engineering implementing various trans-acting RNA platforms, including sRNA, RNAi, asRNA and CRISRP-Cas. In particular, we focus on how the scalable and multiplex nature of trans-acting RNAs has been used to tackle the challenges in creating genome-wide and combinatorial diversity for functional genomics and metabolic engineering applications. Advances in computational design and context-dependent regulation are also discussed for their contribution in improving fine-tuning capabilities of trans-acting RNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Innovative farmers and regulatory gatekeepers: Genetically modified crops regulation and adoption in developing countries.

Science.gov (United States)

Sinebo, Woldeyesus; Maredia, Karim

2016-01-02

The regulation of genetically modified (GM) crops is a topical issue in agriculture and environment over the past 2 decades. The objective of this paper is to recount regulatory and adoption practices in some developing countries that have successfully adopted GM crops so that aspiring countries may draw useful lessons and best practices for their biosafatey regulatory regimes. The first 11 mega-GM crops growing countries each with an area of more than one million hectares in 2014 were examined. Only five out of the 11 countries had smooth and orderly adoption of these crops as per the regulatory requirement of each country. In the remaining 6 countries (all developing countries), GM crops were either introduced across borders without official authorization, released prior to regulatory approval or unapproved seeds were sold along with the approved ones in violation to the existing regulations. Rapid expansion of transgenic crops over the past 2 decades in the developing world was a result of an intense desire by farmers to adopt these crops irrespective of regulatory roadblocks. Lack of workable biosafety regulatory system and political will to support GM crops encouraged unauthorized access to GM crop varieties. In certain cases, unregulated access in turn appeared to result in the adoption of substandard or spurious technology which undermined performance and productivity. An optimal interaction among the national agricultural innovation systems, biosafety regulatory bodies, biotech companies and high level policy makers is vital in making a workable regulated progress in the adoption of GM crops. Factoring forgone opportunities to farmers to benefit from GM crops arising from overregulation into biosafety risk analysis and decision making is suggested. Building functional biosafety regulatory systems that balances the needs of farmers to access and utilize the GM technology with the regulatory imperatives to ensure adequate safety to the environment and human

National Program Initiative to Prevent Illicit Trafficking for Radioactive Materials Out of Regulatory Control at the Border

International Nuclear Information System (INIS)

Suharyanta, S.

2016-01-01

The existing function of regulatory authority in a country which use a lot of radioactive sources is important key. The regulatory body has to in a position independence from other operators and nuclear research centre activities, so that their justification on Regulatory objective of safety and security can be achieved. The essential function of regulatory authority has to be represented such as development regulations, perform review and assessment, inspection and enforcement, and emergency preparedness and response functions. Under regulatory object coverage is divided into two clusters i.e. licensed nuclear installation and radiation facilities clusters,. There is other regulatory object is radioactive material out of regulatory control. This kind object is new option in the county and there for need priority policy judgement. This paper will discuss the Regulatory infrastructure and functions and it focused on the experience about National Programme Initiative to Prevent Illicit Trafficking for Radioactive Materials out of Regulatory Control at the Border. Regulatory Infrastructure and Functions. In Indonesia the independent regulatory authority ''called BAPETEN'' has been established since early 2000 based on the Act No. 10 year 1997, independent from operator organization and other nuclear research centre. Organization structure of BAPETEN has defined main divisions dealing with developing regulations, perform review and assessments, inspection and enforcement, and emergency preparedness and response, and also covered assessment function as a backup technical support division as a think-tank functions. Regulatory objects are nuclear installations such as three research reactors, Fuel fabrication facility, Isotope production facility, and waste storage facility for spent fuel and dis-used radioactive sources is running well. Recently, Regulatory of radioactive sources out of regulatory control is a new challenges, they need strengthened

Safeguards inventory and process monitoring regulatory comparison

Energy Technology Data Exchange (ETDEWEB)

Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

2013-06-27

Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

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

Science.gov (United States)

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

2017-01-01

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

32 CFR 537.19 - Demands arising from maritime claims.

Science.gov (United States)

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Demands arising from maritime claims. 537.19 Section 537.19 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY CLAIMS AND ACCOUNTS CLAIMS ON BEHALF OF THE UNITED STATES § 537.19 Demands arising from maritime claims. (a) It is...

Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan.

Science.gov (United States)

Halioua-Haubold, Celine-Lea; Peyer, James G; Smith, James A; Arshad, Zeeshaan; Scholz, Matthew; Brindley, David A; MacLaren, Robert E

2017-12-01

Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive approaches

CSIR Research Space (South Africa)

Musee, N

2012-05-01

Full Text Available -1 NANOLCA Symposium, "Safety issues and regulatory challenges of nanomaterials", San Sebastian, Spain, 3-4 May 2012 Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive...

Regulating Nuclear Reactor Construction and Commissioning, and Preparation for Operation – Challenges for a New Regulatory Body

International Nuclear Information System (INIS)

Viktorsson, C.

2016-01-01

Following an introduction with a description of the peaceful nuclear energy program in the United Arab Emirates (UAE) and an overview of the regulatory framework for safety, security and safeguards, this paper describes the regulatory approach for oversight of construction and the granting of an Operating Licence for the first nuclear power plant in the UAE. The paper describes the inspection programme set up by the Federal Authority for Nuclear Regulation (FANR) to verify construction and preoperational testing by the licensee. Moreover, it outlines the content of the operating licence application and focus areas for the regulatory review and assessment. Also, the paper describes the basic elements required by FANR for the decision-making regarding the issuance of the Operating Licence including integration of the results of review and assessment and the implementation of a systematic inspection programme to ensure operational readiness to operate and maintain the plant in accordance with FANR regulations. Finally, the paper addresses the preparation for regulatory oversight and the skill-set needed at FANR to ensure an effective and efficient oversight of safety, security of the nuclear energy power in the UAE. (author)

Using Linked Electronic Health Records to Estimate Healthcare Costs: Key Challenges and Opportunities.

Science.gov (United States)

Asaria, Miqdad; Grasic, Katja; Walker, Simon

2016-02-01

This paper discusses key challenges and opportunities that arise when using linked electronic health records (EHR) in health economics and outcomes research (HEOR), with a particular focus on estimating healthcare costs. These challenges and opportunities are framed in the context of a case study modelling the costs of stable coronary artery disease in England. The challenges and opportunities discussed fall broadly into the categories of (1) handling and organising data of this size and sensitivity; (2) extracting clinical endpoints from datasets that have not been designed and collected with such endpoints in mind; and (3) the principles and practice of costing resource use from routinely collected data. We find that there are a number of new challenges and opportunities that arise when working with EHR compared with more traditional sources of data for HEOR. These call for greater clinician involvement and intelligent use of sensitivity analysis.

Towards a predictive theory for genetic regulatory networks

Science.gov (United States)

Tkacik, Gasper

When cells respond to changes in the environment by regulating the expression levels of their genes, we often draw parallels between these biological processes and engineered information processing systems. One can go beyond this qualitative analogy, however, by analyzing information transmission in biochemical ``hardware'' using Shannon's information theory. Here, gene regulation is viewed as a transmission channel operating under restrictive constraints set by the resource costs and intracellular noise. We present a series of results demonstrating that a theory of information transmission in genetic regulatory circuits feasibly yields non-trivial, testable predictions. These predictions concern strategies by which individual gene regulatory elements, e.g., promoters or enhancers, read out their signals; as well as strategies by which small networks of genes, independently or in spatially coupled settings, respond to their inputs. These predictions can be quantitatively compared to the known regulatory networks and their function, and can elucidate how reproducible biological processes, such as embryonic development, can be orchestrated by networks built out of noisy components. Preliminary successes in the gap gene network of the fruit fly Drosophila indicate that a full ab initio theoretical prediction of a regulatory network is possible, a feat that has not yet been achieved for any real regulatory network. We end by describing open challenges on the path towards such a prediction.

A Process Perspective on Regulation: A Grounded Theory Study into Regulatory Practice in Newly Liberalized Network-Based Markets

NARCIS (Netherlands)

Ubacht, J.

The transition from a former monopolistic towards a more competitive market in
newly liberalized network-based markets raises regulatory issues. National Regulatory Authorities (NRA) face the challenge to deal with these issues in order to guide the transition process. Although this transition

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

Science.gov (United States)

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.

Nuclear regulatory organisations: Learning from stakeholders to enhance communication

International Nuclear Information System (INIS)

Lorin, Aurelie

2015-01-01

Since its creation 15 years ago, the NEA Committee on Nuclear Regulatory Activities (CNRA) Working Group on Public Communication of Nuclear Regulatory Organisations (WGPC) has been addressing a broad range of communication issues, with two reports recently issued on Nuclear Regulatory Organisations, the Internet and Social Media: The What, How and Why of Their Use as Communication Tools and on Nuclear Regulatory Organisations and Communication Strategies. After the Fukushima Daiichi nuclear power plant accident in 2011, nuclear regulatory organisations around the world reaffirmed the need to strengthen stakeholder outreach and communication, and to create more robust avenues for stakeholder involvement in regulatory matters. The WGPC proposed a means for stakeholders to play a more active role in the group by holding one-day workshops in conjunction with regular meetings. These workshops offer a platform for stakeholder exchange with communication experts from nuclear regulatory organisations (NROs). The objective is to stimulate co-operation and improve communication by better understanding stakeholder perceptions, needs and expectations, and by discussing how to use traditional and social media more effectively. While nuclear regulatory organisations may have a common willingness to improve their communication methods and to build constructive relationships with stakeholders, every country has its own practices and cultural background, and thus its own challenges. Following the first workshop in Paris, which brought together European stakeholders, and the second in North America, the NEA is now organising a third workshop in Asia (Japan) to be held in April 2016. This third workshop will enable the NEA to gather stakeholder views from a third continent. A report on the workshops' findings will be issued after the completion of this third workshop, thus giving a broader idea of how to improve the overall communication methods of nuclear regulatory

Four Different Tumors Arising in a Nevus Sebaceous

Directory of Open Access Journals (Sweden)

Takeshi Namiki

2016-04-01

Full Text Available Nevus sebaceous is known by its association with one or more secondary tumors, but more than three multiple tumors arising from a nevus sebaceous is extremely rare. A 67-year-old female presented with a light brown plaque on the back of her head that contained a dome-shaped black node and an erosive lesion. Histopathological examination showed atypical basaloid cells in the black node. At the periphery of that node, structures resembling follicular germs extruded from interlacing cords in the upper portion and tumor nests with sebocytes were in the lower portion. In the erosive lesion, papillated structures with an apocrine epithelium were observed. In the light brown plaque, enlargement of sebaceous lobules was noted. From those histopathological features, a diagnosis of syringocystadenoma papilliferum, sebaceoma, trichoblastoma and basal cell carcinoma arising from a nevus sebaceous was made. We discuss the rarity of multiple tumors arising from a nevus sebaceous.

The European Medicines Agency's strategies to meet the challenges of Alzheimer disease.

Science.gov (United States)

Haas, Manuel; Mantua, Valentina; Haberkamp, Marion; Pani, Luca; Isaac, Maria; Butlen-Ducuing, Florence; Vamvakas, Spiros; Broich, Karl

2015-04-01

Regulatory agencies have a key role in facilitating the development of new drugs for Alzheimer disease, particularly given the challenges associated with early intervention. Here, we highlight the strategies of the European Medicines Agency to help address such challenges.

Challenges for decommissioning policies

International Nuclear Information System (INIS)

Riotte, H.

2007-01-01

In the coming years, OECD member countries will be increasingly faced with the need to make appropriate provisions, in terms of policy, finance and management, for all aspects of decommissioning. Decommissioning requires regulatory approval and oversight, the directions of which are guided by national policy. In several instances, governments have only recently begun to address their approaches to decommissioning policy and regulation in national legislation, and international overviews of such approaches, which may eventually lead to international harmonization, are only now beginning to emerge. In parallel, policy and regulation have been evolving and a broadened competence has developed in relevant regulatory authorities. The challenge lying ahead is to establish a framework that will allow for the growth of nuclear industrial activities in competitive, globalized markets, while maintaining and assuring the safety of decommissioning for the public and for workers. Within this context, institutional arrangements, stakeholder issues, costs and funding, waste management and policies for release from regulatory control, as well as the availability of technologies and skills, need to be reviewed. (author)

The role of women in nuclear - attracting public participation in regulatory decision-making process

Science.gov (United States)

Mohamad Jais, Azlina; Hassan, Najwa

2018-01-01

Public participation is vital in demonstrating transparency and enhancing effectiveness of a nuclear regulatory process. As such, it is necessary for nuclear practitioners to involve the public in key nuclear delivery milestones. This paper specifically discusses challenges faced in attracting public participation throughout the nuclear regulatory decision-making process, and highlights the roles of women in nuclear (WiN) in initiating the said public discourse.

Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection.

Science.gov (United States)

Shi, Jiandong; Sun, Jing; Wang, Bin; Wu, Meini; Zhang, Jing; Duan, Zhiqing; Wang, Haixuan; Hu, Ningzhu; Hu, Yunzhang

2014-10-01

MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs. © FASEB.

Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells.

Directory of Open Access Journals (Sweden)

Cyndi Chen

Full Text Available BACKGROUND: Both naturally arising Foxp3(+ and antigen-induced Foxp3(- regulatory T cells (Treg play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel class II MHC tetramer, we have isolated a population of CD4(+ Foxp3(- T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells from diabetes-resistant non-obese resistant (NOR mice. These Foxp3(- NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. CONCLUSIONS/SIGNIFICANCE: These studies identified a unique population of autoantigen-specific Foxp3(- Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.

Challenges Involved in the Development and Delivery of Abuse-deterrent Formulations of Opioid Analgesics.

Science.gov (United States)

Cohen, Joshua P; Mendoza, Mario; Roland, Carl

2018-02-01

This commentary examines the development, regulatory, and reimbursement challenges facing abuse-deterrent formulation (ADF) products. In January 2017, the Tufts Center for the Study of Drug Development convened a roundtable to explore clinical development, regulatory, and reimbursement challenges with respect to ADFs of opioid analgesics. Roundtable participants, who included a range of pharmaceutical industry and other experts, discussed multiple challenges. First, several key clinical development challenges were identified and discussed. These challenges pertain to prodrug development and development of deterrents against oral abuse. Second, experts suggested that more clarity is needed from regulatory authorities regarding standards for proving ADF labeling claims and for being rewarded with 3-year data exclusivity. Similarly, given the substantial burdens associated with the development of postapproval evidence generation, experts raised the need for a consistent regulatory policy related to postapproval evidence generation for all ADFs (branded and generic). Third, despite the public health benefits of certain ADF products, current coverage and access policies impede patient access. Payer justification for restrictive policies appears to be based more on budget impact considerations than cost-effectiveness. Fourth, there remains a need to further expand the evidence base regarding clinical and cost-effectiveness as well as abuse deterrence in a real-world setting for all ADF products. Clinical development challenges need to be overcome with respect to novel ADF technologies, such as prodrugs and deterrents against oral abuse. More clarity is needed from regulatory authorities on labeling claims and data exclusivity eligibility with respect to ADFs. Ensuring prescriber training and awareness of various options for treating pain, including ADF products, is an important step, as is educating payers about the public health benefits of ADFs in appropriate

Towards new regulatory concepts for the regulation of audiovisual media

NARCIS (Netherlands)

Schulz, W.; van Eijk, N.

2016-01-01

European media regulation currently faces several challenges: technology, media and markets have become convergent, while – at the same time – the situations in the individual member states differ in respect of media use, the usage of end devices as well as regulatory aims and frameworks. These

Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

DEFF Research Database (Denmark)

Zelezniak, Aleksej; Pers, Tune Hannes; Pinho Soares, Simao Pedro

2010-01-01

mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets...... with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment...... factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic...

Conjunctival lymphoma arising from reactive lymphoid hyperplasia

Directory of Open Access Journals (Sweden)

Fukuhara Junichi

2012-09-01

Full Text Available Abstract Extra nodal marginal zone B-cell lymphoma (EMZL of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU. Specimens from conjunctival tumors in the right eye, oculus dexter (OD, revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS, and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

Towards addressing transient learning challenges in undergraduate physics: an example from electrostatics

Science.gov (United States)

Fredlund, T.; Linder, C.; Airey, J.

2015-09-01

In this article we characterize transient learning challenges as learning challenges that arise out of teaching situations rather than conflicts with prior knowledge. We propose that these learning challenges can be identified by paying careful attention to the representations that students produce. Once a transient learning challenge has been identified, teachers can create interventions to address it. By illustration, we argue that an appropriate way to design such interventions is to create variation around the disciplinary-relevant aspects associated with the transient learning challenge.

32 CFR 536.111 - Investigation of claims arising under international agreements (for those claims arising in the...

Science.gov (United States)

2010-07-01

... under international agreements (for those claims arising in the United States). Responsibility for... civilian component is attached, including the legal office of another armed force, to carry out the responsibility to investigate. The investigation will comply with the responsible Service's implementing claims...

Issues, challenges, and approaches for risk-informed decommissioning in the United States

International Nuclear Information System (INIS)

Orlando, D.A.; Johnson, R.L.

2005-01-01

Full text: The U.S. Nuclear Regulatory Commission (US-NRC) is the principal Federal regulatory authority in the United States responsible for ensuring public health and safety from the civilian use of radioactive material. US-NRC staff has developed and implemented various risk-informed approaches for regulating and managing the remediation of contaminated sites. A risk-informed approach to regulating the decommissioning of nuclear facilities has been generally defined by the US-NRC staff as an approach to decision-making that uses risk insights as well as traditional considerations to focus regulator and licensee attention on decommissioning activities commensurate with their importance to health and safety. Ensuring that decommissioning is carried out using a risk-informed approach should improve the focus on safety in decommissioning, improve the effectiveness, efficiency, and realism in regulatory decisions, and reduce unnecessary regulatory burden, and cost, on licensees. This paper summarizes the efforts by the US-NRC to develop and implement risk-informed approaches to the remediation of nuclear facilities in the United States. It also discusses the issues and challenges encountered by the US-NRC in attempting to implement a risk-informed approach to decommissioning. The US-NRC has been incrementally implementing its existing risk-informed and performance-based approach as it has completed its decommissioning regulations, guidance and other tools over the past several years. The principal challenge for US-NRC is implementing the existing risk-informed approach at specific sites in a manner that maintains safety, reduces costs, and enhances public understanding of the US-NRC's approach. In addition, effectively communicating how the US-NRC approaches are risk-informed and performance-based; ensuring that licensees understand, and take advantage of, the flexibility in meeting the decommissioning goals; ensuring that licensees and staff are aware of the

Squamous cell carcinoma arising in mature cystic teratoma of ovary

Directory of Open Access Journals (Sweden)

Ranu Patni

2014-01-01

Full Text Available Squamous cell carcinoma of the ovary is a rare condition and usually arises in mature cystic teratoma (MCT or dermoid cyst of the ovary. The reported incidence of malignant transformation in MCT is approximately 2%. A case of squamous cell carcinoma arising in a dermoid cyst of the ovary presenting at an early stage is presented here. A 53-year-old postmenopausal lady, presented with the complaint of pain in right lower abdomen since one month and a large complex abdomino-pelvic mass on examination and investigations. Final histopathology was reported as squamous cell carcinoma of left ovary arising from dermoid cyst and a benign dermoid cyst in the right ovary. The patient was assigned to squamous cell carcinoma of the ovary arising in a mature cystic teratoma, surgical stage Ic2. In view of the poor prognosis, adjuvant chemotherapy was started.

Continuing challenges in nuclear air cleaning

International Nuclear Information System (INIS)

Moeller, D.W.

1976-01-01

The safe operation of nuclear facilities is heavily dependent upon the adequate performance of air cleaning systems. Although many problems have been solved, new questions and new challenges continue to arise. These are well illustrated by weaknesses in air cleaning and ventilating systems revealed by the Browns Ferry fire, and the need to develop additional data on the reliability of such systems, particularly under emergency conditions, as revealed by the Reactor Safety Study. Assessments of the degree to which engineered safety features can compensate for deficiencies in nuclear power plant sites continue to challenge those involved in risk/benefit evaluations. Additional challenges are being generated by the air cleaning requirements associated with the commercial development of the liquid metal fast breeder reactor

Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

Science.gov (United States)

Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

2015-01-01

The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2010-01-01

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.

Inferring Gene Regulatory Networks Using Conditional Regulation Pattern to Guide Candidate Genes.

Directory of Open Access Journals (Sweden)

Fei Xiao

Full Text Available Combining path consistency (PC algorithms with conditional mutual information (CMI are widely used in reconstruction of gene regulatory networks. CMI has many advantages over Pearson correlation coefficient in measuring non-linear dependence to infer gene regulatory networks. It can also discriminate the direct regulations from indirect ones. However, it is still a challenge to select the conditional genes in an optimal way, which affects the performance and computation complexity of the PC algorithm. In this study, we develop a novel conditional mutual information-based algorithm, namely RPNI (Regulation Pattern based Network Inference, to infer gene regulatory networks. For conditional gene selection, we define the co-regulation pattern, indirect-regulation pattern and mixture-regulation pattern as three candidate patterns to guide the selection of candidate genes. To demonstrate the potential of our algorithm, we apply it to gene expression data from DREAM challenge. Experimental results show that RPNI outperforms existing conditional mutual information-based methods in both accuracy and time complexity for different sizes of gene samples. Furthermore, the robustness of our algorithm is demonstrated by noisy interference analysis using different types of noise.

International Conference on Effective Nuclear Regulatory Systems: Sustaining Improvements Globally. Book of Abstracts

International Nuclear Information System (INIS)

2016-01-01

The objective of this conference is to review and assess ways of further improving the effectiveness of regulatory systems for nuclear facilities and activities for both nuclear safety and nuclear security. The action items in the summary presented by the President of the conference held in 2013 in Ottawa, the lessons of the Fukushima Daiichi accident, the discussions at other international conferences and at international experts’ meetings conducted within the framework of the IAEA Action Plan on Nuclear Safety, as well as the CNS and the principles outlined in the Vienna Declaration on Nuclear Safety, will continue to have a significant impact on regulatory systems. All the aforementioned need to be taken into account to sustain improvements to regulatory systems. The expected outcomes of the conference are: - Enhanced safety and security of nuclear installations worldwide; - Challenges in regulating radiation sources and radioactive waste addressed; - Enhanced international cooperation for sustaining regulatory effectiveness; - Strengthened and sustained regulatory competence for nuclear safety and security; and - Strategies and actions for the future identified, as well as issues for consideration by governments, regulatory bodies and international organizations.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

Science.gov (United States)

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

Strategies to Address Common Challenges When Teaching in an Active Learning Classroom

Science.gov (United States)

Petersen, Christina I.; Gorman, Kristen S.

2014-01-01

This chapter provides practical strategies for addressing common challenges that arise for teachers in active learning classrooms. Our strategies come from instructors with experience teaching in these environments.

Expert Views on Regulatory Preparedness for Managing the Risks of Nanotechnologies

Science.gov (United States)

Beaudrie, Christian E. H.; Satterfield, Terre; Kandlikar, Milind; Harthorn, Barbara H.

2013-01-01

The potential and promise of nanotechnologies depends in large part on the ability for regulatory systems to assess and manage their benefits and risks. However, considerable uncertainty persists regarding the health and environmental implications of nanomaterials, hence the capacity for existing regulations to meet this challenge has been widely questioned. Here we draw from a survey (N=254) of US-based nano-scientists and engineers, environmental health and safety scientists, and regulatory scientists and decision-makers, to ask whether nano experts regard regulatory agencies as prepared for managing nanomaterial risks. We find that all three expert groups view regulatory agencies as unprepared. The effect is strongest for regulators themselves, and less so for scientists conducting basic, applied, or health and safety work on nanomaterials. Those who see nanotechnology risks as novel, uncertain, and difficult to assess are particularly likely to see agencies as unprepared. Trust in regulatory agencies, views of stakeholder responsibility regarding the management of risks, and socio-political values were also found to be small but significant drivers of perceived agency preparedness. These results underscore the need for new tools and methods to enable the assessment of nanomaterial risks, and to renew confidence in regulatory agencies’ ability to oversee their growing use and application in society. PMID:24244662

Expert views on regulatory preparedness for managing the risks of nanotechnologies.

Directory of Open Access Journals (Sweden)

Christian E H Beaudrie

Full Text Available The potential and promise of nanotechnologies depends in large part on the ability for regulatory systems to assess and manage their benefits and risks. However, considerable uncertainty persists regarding the health and environmental implications of nanomaterials, hence the capacity for existing regulations to meet this challenge has been widely questioned. Here we draw from a survey (N=254 of US-based nano-scientists and engineers, environmental health and safety scientists, and regulatory scientists and decision-makers, to ask whether nano experts regard regulatory agencies as prepared for managing nanomaterial risks. We find that all three expert groups view regulatory agencies as unprepared. The effect is strongest for regulators themselves, and less so for scientists conducting basic, applied, or health and safety work on nanomaterials. Those who see nanotechnology risks as novel, uncertain, and difficult to assess are particularly likely to see agencies as unprepared. Trust in regulatory agencies, views of stakeholder responsibility regarding the management of risks, and socio-political values were also found to be small but significant drivers of perceived agency preparedness. These results underscore the need for new tools and methods to enable the assessment of nanomaterial risks, and to renew confidence in regulatory agencies' ability to oversee their growing use and application in society.

A new way of teaching an old subject: Pharmacy Law and Ethics ...

African Journals Online (AJOL)

Background. Pharmacy educators are responsible for ensuring that students are equipped with the necessary regulatory knowledge required to deal with ethical challenges that arise in practice. Teaching methods have a strong impact on student learning, making it essential to determine how learning is influenced when ...

ARISE: American renaissance in science education

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-14

The national standards and state derivatives must be reinforced by models of curricular reform. In this paper, ARISE presents one model based on a set of principles--coherence, integration of the sciences, movement from concrete ideas to abstract ones, inquiry, connection and application, sequencing that is responsive to how people learn.

Squamous Cell Carcinoma of the Larynx Arising in Multifocal Pharyngolaryngeal Oncocytic Papillary Cystadenoma

Science.gov (United States)

Stenner, Markus; Müller, Klaus-Michael; Koopmann, Mario; Rudack, Claudia

2014-01-01

Abstract We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well. PMID:25211046

Steering healthcare service delivery: a regulatory perspective.

Science.gov (United States)

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.

Issues arising in applying the BSS concepts

International Nuclear Information System (INIS)

Linsley, G.

1997-01-01

The following issues are discussed arising in applying the basic safety standard concepts: terminology, naturally occurring radionuclides, the exemption and clearance levels, management of very low level wastes, transboundary movements, the waste convention

Salinity- and population-dependent genome regulatory response during osmotic acclimation in the killifish (Fundulus heteroclitus) gill.

Science.gov (United States)

Whitehead, Andrew; Roach, Jennifer L; Zhang, Shujun; Galvez, Fernando

2012-04-15

The killifish Fundulus heteroclitus is abundant in osmotically dynamic estuaries and it can quickly adjust to extremes in environmental salinity. We performed a comparative osmotic challenge experiment to track the transcriptomic and physiological responses to two salinities throughout a time course of acclimation, and to explore the genome regulatory mechanisms that enable extreme osmotic acclimation. One southern and one northern coastal population, known to differ in their tolerance to hypo-osmotic exposure, were used as our comparative model. Both populations could maintain osmotic homeostasis when transferred from 32 to 0.4 p.p.t., but diverged in their compensatory abilities when challenged down to 0.1 p.p.t., in parallel with divergent transformation of gill morphology. Genes involved in cell volume regulation, nucleosome maintenance, ion transport, energetics, mitochondrion function, transcriptional regulation and apoptosis showed population- and salinity-dependent patterns of expression during acclimation. Network analysis confirmed the role of cytokine and kinase signaling pathways in coordinating the genome regulatory response to osmotic challenge, and also posited the importance of signaling coordinated through the transcription factor HNF-4α. These genome responses support hypotheses of which regulatory mechanisms are particularly relevant for enabling extreme physiological flexibility.

Assisting IAEA Member States to Strengthen Regulatory Control, Particularly in the Medical Area

International Nuclear Information System (INIS)

Johnston, P.

2016-01-01

As per its Statue and Mandate, IAEA is developing Safety Standards and is also providing assistance for their application in Member States. One target and very large audience of this programme is the community of national regulatory bodies for radiation safety, expected to be established in all 168 Member States. Ionizing radiation is being used throughout the world in medical practices and medical exposure is the most significant manmade source of exposure to the population from ionizing radiation. Radiation accidents involving medical uses have accounted for more injuries and early acute health effects than any other type of radiation accident, including accidents at nuclear facilities. With the constant emerging of new technologies using ionizing radiation for medical diagnostic and treatment, there are on-going challenges for Regulatory bodies. The presentation will highlight some figures related to the medical exposure worldwide, and then it will introduce the main safety standards and other publications developed specifically for Regulatory Bodies and focusing on medical practices. It will also highlight the most important and recent mechanisms (tools, peer reviews and advisory services, training courses, networks) that the Agency is offering to its Member States in order to cope with the main challenges worldwide, contributing thus to the efficiency and effectiveness of the regulatory oversight of medical facilities and activities. (author)

The challenges of energy - response to Moody-Stuart

Directory of Open Access Journals (Sweden)

John Houghton

2002-09-01

Full Text Available Sir Mark has lucidly addressed the growing demand for accessible energy throughout the world, the need for basic provision of energy to one third of the world's population and the conflicts that arise between the ways in which energy is supplised and used and the constraints of sustainability. It is, of course, the innovation, creativity and activity of industry that will provide solutions to the problems we face. It is therefore appropriate and helpful to hear form one of the leaders of the energy industry. The vision he presents i one of a vibrant, innovation, market-driven industry operating within a regulatory framework that gives the maximum flexibility for creative solutions. The greatest challenges faced by the world energy sector are concerned with environmental sustainability. Because the emissions of greenhouse gases such as carbon dioxide spread rapidly around the globe, sustainability has to be considered on a global basis and global solutions are rquired. International agreements concerning action, for instance the Framework Convention on Climate Change (FCCC, need to be based on sound science and on four widely accepted principles, namely the Precautionary Principle, the Polluter Pays Principles and the Principles of Sustainable Development and Equity. The challenge to the FCCC is to devise mechanisms and arragements that will bring about substantial reductions in greenhouse gas concentrations in the atmosphere and that also satisfy there principles. A recent Energy Review from the Policy Innovation Unit of the UK Government's Cabinet Office has considered in detail how a sustainable energy strategy can be developed. Finally, reasons are given for optimism that, given the necessary commitment by the world community, a sustainable energy strategy for the world can be developed and realised during the 21st century.

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

Electric reaction arising in bone subjected to mechanical loadings

Science.gov (United States)

Murasawa, Go; Cho, Hideo; Ogawa, Kazuma

2006-03-01

The aim of present study is the investigation of the electric reaction arising in bone subjected to mechanical loadings. Firstly, specimen was fabricated from femur of cow, and ultrasonic propagation in bone was measured by ultrasonic technique. Secondary, 4-point bending test was conducted up to fracture, and electric reaction arising in bone was measured during loading. Thirdly, cyclic 4-point bending test was conducted to investigate the effect of applied displacement speed on electric reaction.

Identifying noncoding risk variants using disease-relevant gene regulatory networks.

Science.gov (United States)

Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

2018-02-16

Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Directory of Open Access Journals (Sweden)

M Venkatesh

2011-01-01

Full Text Available Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20 th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Science.gov (United States)

Venkatesh, M.; Bairavi, V. G.; Sasikumar, K. C.

2011-01-01

Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

Regulatory Compliance in Multi-Tier Supplier Networks

Science.gov (United States)

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.

Harnessing diversity towards the reconstructing of large scale gene regulatory networks.

Directory of Open Access Journals (Sweden)

Takeshi Hase

Full Text Available Elucidating gene regulatory network (GRN from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks.

Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies.

Science.gov (United States)

Hanrahan, Donna; Sexton, Patrina; Hui, Katrina; Teitcher, Jennifer; Sugarman, Jeremy; London, Alex John; Barnes, Mark; Purpura, James; Klitzman, Robert

2015-01-01

Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications--US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies

Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies

Science.gov (United States)

2015-01-01

Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications – US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies

Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies.

Directory of Open Access Journals (Sweden)

Donna Hanrahan

Full Text Available Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN, regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1 context, (2 process, (3 content and (4 translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level, and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh, syntax, manner of questions posed, and the concept of the consent; and the contexts of use affect meaning. Problems also emerged in bilateral communications--US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several

Governing Nanomedicine: Lessons from within, and for the EU medical technology regulatory framework.

NARCIS (Netherlands)

Dorbeck-Jung, Barbel R.; Bowman, Diana M.; van Calster, Geert

2010-01-01

Rapidly emerging technologies, such as nanotechnologies, are posing significant challenges to regulatory governance due to the uncertainties of development trajectories, product properties, and potential risk problems (Davies 2009). While nanotechnology-based products and processes fall within the

Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

Science.gov (United States)

Risso-Gill, Isabelle; Legido-Quigley, H; Panteli, D; Mckee, M

2014-08-01

This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care. © The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Pragmatic application of the precautionary principle to deal with unknown safety challenges

Energy Technology Data Exchange (ETDEWEB)

Frappier, G.; Viktorov, A., E-mail: gerry.frappier@cnsc-ccsn.gc.ca, E-mail: alex.viktorov@cnsc-ccsn.gc.ca [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada)

2011-07-01

Nuclear power technology has matured over a number of decades to the point where our understanding of the technology under a wide variety of circumstances is quite high. Despite this high degree of maturity, discoveries of new challenges occasionally surface. These may arise from either unusual or unexpected operational conditions or new experimental findings from ongoing research. With the early realization that such discoveries could occur, a conscious effort was made to take precautions against their negative impacts. Principles such as defence-in-depth, designing for high reliability, incorporation of robust safety margins and use of justified conservatisms are key examples of established practices that are embedded in national regulatory regimes of most, if not all countries with nuclear programs. Because of these provisions the safety cases of the current generation of reactors proved to be quite resilient to discoveries of earlier unrecognized challenges. A fundamentally important element in the management of “unknown unknowns” is a healthy research programme. Such a programme is especially necessary as a precondition for understanding potential impacts from changes in operating conditions or implementation of novel design features. A research programme helps minimizing chances of stumbling on “unknown unknowns”, and allows resolution of emerging issues to by virtue of the accumulated understanding and capability to predict challenges to safety. In the few instances when discoveries occurred with recognized negative effects on safety, these spurred changes in operating conditions, maintenance or testing practices, design modifications, as well as required targeted research projects. This paper outlines several CANDU-specific “discoveries” in the field of thermalhydraulics, illustrating past “unknown unknowns” and the actions taken to address those. The main message, however, is to point out that both the industry and the regulator should

Pragmatic application of the precautionary principle to deal with unknown safety challenges

International Nuclear Information System (INIS)

Frappier, G.; Viktorov, A.

2011-01-01

Nuclear power technology has matured over a number of decades to the point where our understanding of the technology under a wide variety of circumstances is quite high. Despite this high degree of maturity, discoveries of new challenges occasionally surface. These may arise from either unusual or unexpected operational conditions or new experimental findings from ongoing research. With the early realization that such discoveries could occur, a conscious effort was made to take precautions against their negative impacts. Principles such as defence-in-depth, designing for high reliability, incorporation of robust safety margins and use of justified conservatisms are key examples of established practices that are embedded in national regulatory regimes of most, if not all countries with nuclear programs. Because of these provisions the safety cases of the current generation of reactors proved to be quite resilient to discoveries of earlier unrecognized challenges. A fundamentally important element in the management of “unknown unknowns” is a healthy research programme. Such a programme is especially necessary as a precondition for understanding potential impacts from changes in operating conditions or implementation of novel design features. A research programme helps minimizing chances of stumbling on “unknown unknowns”, and allows resolution of emerging issues to by virtue of the accumulated understanding and capability to predict challenges to safety. In the few instances when discoveries occurred with recognized negative effects on safety, these spurred changes in operating conditions, maintenance or testing practices, design modifications, as well as required targeted research projects. This paper outlines several CANDU-specific “discoveries” in the field of thermalhydraulics, illustrating past “unknown unknowns” and the actions taken to address those. The main message, however, is to point out that both the industry and the regulator should

Genome-wide comparative analysis reveals human-mouse regulatory landscape and evolution.

Science.gov (United States)

Denas, Olgert; Sandstrom, Richard; Cheng, Yong; Beal, Kathryn; Herrero, Javier; Hardison, Ross C; Taylor, James

2015-02-14

Because species-specific gene expression is driven by species-specific regulation, understanding the relationship between sequence and function of the regulatory regions in different species will help elucidate how differences among species arise. Despite active experimental and computational research, relationships among sequence, conservation, and function are still poorly understood. We compared transcription factor occupied segments (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and tissues from the Human and the Mouse ENCODE projects. We based the map between human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper, that utilizes whole genome alignments (WGA). Our analysis shows that TFos are under evolutionary constraint, but a substantial portion (25.1% of mouse and 25.85% of human on average) of the TFos does not have a homologous sequence on the other species; this portion varies among cell types and TFs. Furthermore, 47.67% and 57.01% of the homologous TFos sequence shows binding activity on the other species for human and mouse respectively. However, 79.87% and 69.22% is repurposed such that it binds the same TF in different cells or different TFs in the same cells. Remarkably, within the set of repurposed TFos, the corresponding genome regions in the other species are preferred locations of novel TFos. These events suggest exaptation of some functional regulatory sequences into new function. Despite TFos repurposing, we did not find substantial changes in their predicted target genes, suggesting that CRMs buffer evolutionary events allowing little or no change in the TFos - target gene associations. Thus, the small portion of TFos with strictly conserved occupancy underestimates the degree of conservation of regulatory interactions. We mapped regulatory sequences from an extensive number of TFs and cell types between human and mouse using WGA. A comparative analysis of this correspondence unveiled the

Self-regulatory fatigue in hematologic malignancies: impact on quality of life, coping, and adherence to medical recommendations.

Science.gov (United States)

Solberg Nes, Lise; Ehlers, Shawna L; Patten, Christi A; Gastineau, Dennis A

2013-03-01

Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.

Law of the Energy Regulatory Commission

International Nuclear Information System (INIS)

1995-01-01

This Decree-Law consist of three chapters each on divided in articles and subsections and came into force in November 1 st., 1995. Chapter I, with the heading 'Nature and Powers', defines the Energy Regulatory Commission as a decentralized organ of the Energy Secretariat with technical and operative autonomy in terms of the law, and establish the conditions for the sell, generation, exportation and importation of electricity with destination to particular and public services. The sell transport, storage and distribution of natural gas, as well as the gas liquefied from petroleum are also considered. Chapter II with the heading 'Organization and duties' establish that the Commission is integrated by five Committee, the President included. The Committee members will deliberate in collegiate manner and the decisions are by majority, having the President a vote of quality. Chapter III for 'General provisions' is related to the lawsuits arises between the Commission and the users of services. (Author)

Industrial Adoption of Model-Based Systems Engineering: Challenges and Strategies

Science.gov (United States)

Maheshwari, Apoorv

As design teams are becoming more globally integrated, one of the biggest challenges is to efficiently communicate across the team. The increasing complexity and multi-disciplinary nature of the products are also making it difficult to keep track of all the information generated during the design process by these global team members. System engineers have identified Model-based Systems Engineering (MBSE) as a possible solution where the emphasis is placed on the application of visual modeling methods and best practices to systems engineering (SE) activities right from the beginning of the conceptual design phases through to the end of the product lifecycle. Despite several advantages, there are multiple challenges restricting the adoption of MBSE by industry. We mainly consider the following two challenges: a) Industry perceives MBSE just as a diagramming tool and does not see too much value in MBSE; b) Industrial adopters are skeptical if the products developed using MBSE approach will be accepted by the regulatory bodies. To provide counter evidence to the former challenge, we developed a generic framework for translation from an MBSE tool (Systems Modeling Language, SysML) to an analysis tool (Agent-Based Modeling, ABM). The translation is demonstrated using a simplified air traffic management problem and provides an example of a potential quite significant value: the ability to use MBSE representations directly in an analysis setting. For the latter challenge, we are developing a reference model that uses SysML to represent a generic infusion pump and SE process for planning, developing, and obtaining regulatory approval of a medical device. This reference model demonstrates how regulatory requirements can be captured effectively through model-based representations. We will present another case study at the end where we will apply the knowledge gained from both case studies to a UAV design problem.

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

Science.gov (United States)

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

2017-10-01

Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

Science.gov (United States)

O'Connor, Timothy R.; Bailey, Timothy L.

2014-01-01

Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

Politically Induced Regulatory Risk and Independent Regulatory Agencies

OpenAIRE

Strausz, Roland

2015-01-01

Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

Regulatory control and challenges in Medical facilities using ionising radiation sources

International Nuclear Information System (INIS)

Agarwal, S.P.

2008-01-01

Medical facilities utilising ionising radiation sources for diagnostic and treatment of cancer are regulated under the provisions of Atomic Energy (Radiation Protection) Rules, 2004 promulgated under the Atomic Energy Act 1962. The Competent Authority for the enforcement of the rules is Chairman, Atomic Energy Regulatory Board (AERB). Practice specific codes are issued by AERB for medical facilities such as Radiotherapy, Nuclear Medicine and Radiology. Regulatory process for control of medical facilities covers the entire life cycle of the radiation sources in three stages viz pre-Iicensing, during useful life and decommissioning and disposal. Pre-Iicensing requirements include use of type approved sources and equipment, approval of design layout of the facility and installation, exclusive (safe and secure) source storage facility when the equipment is not in use, radiation (area/individual) monitoring devices, qualified, trained and certified manpower, emergency response plans and commitment from the licensee for the safe disposal of disused/decayed sources. Compliance to these requirements makes the applicant eligible to obtain license from AERB for the operation of the medical facility. During the use of radiation sources, specific prior approval of the Competent Authority is required in respect of every source replacement, sale, transfer, transport, import and export. Further, all licensees are required to send the periodic safety Status reports to AERB as well as reporting of any off normal events. AERB conducts inspection of the facilities to ensure compliance with the safety requirements during operation of the facility. Violation of safety norms by licensee attracts enforcement action which includes suspension, modification or withdrawal of licensee for operation of the facility. Upon completion of the useful life of the source, the licensee decommissions the facility and returns the source to the original supplier. For returning the source, prior

Regulatory dendritic cell therapy: from rodents to clinical application.

Science.gov (United States)

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

2014-10-01

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

Distributed generation in European electricity markets. Current challenges and future opportunities

Energy Technology Data Exchange (ETDEWEB)

Ropenus, S. (Technical Univ. of Denmark, Risoe National Lab. for Sustainable Energy. Systems Analysis Div., Roskilde (Denmark))

2010-07-01

This Ph.D. thesis studies the role of distributed generation in European electricity markets. It focuses primarily on the interactions of economics and policy with the aim of contributing to the understanding of how distributed generation is embedded in the present regulatory and market framework, which barriers exist, and which role it may possibly play in the future. To capture the interdisciplinarity of the topic, a combination of qualitative and quantitative methods is applied. Subsequent to the identification of barriers, this thesis turns to the microeconomic perspective on the interplay of vertical structure, regulation and distributed generation. This is done through the application of quantitative methods in the form of partial equilibrium models focusing on the effects induced by the vertical structure of the network operator, either a combined operator or a distribution system operator, in a market with small distributed producers. In areas where the promotion of renewable energy sources and combined heat and power has induced a substantial increase in distributed generation, new challenges in system integration arise. In particular, high levels of generation from intermittent energy sources, such as wind, add to the complexity of network operation and control, which can hardly be tackled with the present 'fit and forget' approach. The conclusion is that distributed generation has great potential to enhance competitiveness, sustainability and security of supply in European electricity markets. A prerequisite is the removal of market and regulatory barriers, taking the interdependencies of vertical structure, support mechanisms and network access into account. In the future, higher penetration levels of distributed generation necessitate changes in the power system and the adoption of new technologies, where hydrogen production by grid connected electrolysis constitutes one example. (LN)

Technical support organization of national regulators: Challenges and strategy

International Nuclear Information System (INIS)

Mallick, S.A.; Maqbul, N.; Kanwal, S.; Hashmi, J.A.

2007-01-01

technical support organization called the 'Centre for Nuclear Safety' within PNRA to meet the future regulatory challenges. This paper discusses the objectives and organization of Centre for Nuclear Safety and the challenges that the centre is facing as the strategy being devised to meet those challenges. The paper includes a brief description of co-operation under an IAEA TC project titled 'Further Improvement of Nuclear Regulatory Infrastructure in Pakistan-(PAK/9/28)' which is an example of international co-operation in the establishment of technical support organization to enhance the regulatory effectiveness of the national regulator in Pakistan. (author)

Challenges in conducting a community-based influenza vaccine trial in a rural community in northern India.

Science.gov (United States)

Kumar, Rakesh; Amarchand, Ritvik; Narayan, Venkatesh Vinayak; Saha, Siddhartha; Lafond, Kathryn E; Kapoor, Suresh K; Dar, Lalit; Jain, Seema; Krishnan, Anand

2018-04-04

Evidence on influenza vaccine effectiveness from low and middle countries (LMICs) is limited due to limited institutional capacities; lack of adequate resources; and lack of interest by ministries of health for influenza vaccine introduction. There are concerns that the highest ethical standards will be compromised during trials in LMICs leading to mistrust of clinical trials. These factors pose regulatory and operational challenges to researchers in these countries. We conducted a community-based vaccine trial to assess the efficacy of live attenuated influenza vaccine and inactivated influenza vaccine in rural north India. Key regulatory challenges included obtaining regulatory approvals, reporting of adverse events, and compensating subjects for trial-related injuries; all of which were required to be completed in a timely fashion. Key operational challenges included obtaining audio-visual consent; maintaining a low attrition rate; and administering vaccines during a narrow time period before the influenza season, and under extreme heat. We overcame these challenges through advanced planning, and sustaining community engagement. We adapted the trial procedures to cope with field conditions by conducting mock vaccine camps; and planned for early morning vaccination to mitigate threats to the cold chain. These lessons may help investigators to confront similar challenges in other LMICs.

Transitioning from first- to second-generation biosimilars: An appraisal of regulatory and post-marketing challenges.

Science.gov (United States)

Blandizzi, Corrado; Galeazzi, Mauro; Valesini, Guido

2018-02-01

Second-generation biosimilars (i.e. monoclonal antibodies or proteins generated by fusion of antibody and receptor moieties) differ in several respects as compared to first-generation ones (e.g. epoetins, bone marrow stimulating factors, somatotropins). In this respect, as second-generation biosimilars are endowed with much greater structural and molecular complexity, which might translate into a number of pharmacological and therapeutic issues, they raise new challenges for manufacturers and regulatory authorities as well as new concerns for clinicians. Based on these arguments, the present article was intended to review information on the main differences between first- and second-generation biosimilars for treatment of immune-mediated inflammatory diseases, as well as their impact on immunogenicity, the design of clinical trials and the critical issue of extrapolation of therapeutic indications. The positions taken by relevant medical associations and the crucial role of pharmacovigilance are also reviewed. According to current knowledge, the initial post-marketing clinical experience with second-generation biosimilars is providing encouraging results, though their long-term safety and efficacy as well as the scientific basis underlying the extrapolation of therapeutic indications are still matter of discussion. There is some consensus that marketing applications should rely on studies supporting the clinical use of biosimilars in their different target diseases and patient populations. In parallel, clinical safety must be ensured by a strict control of the manufacturing processes and a solid pharmacovigilance program. It remains then a responsibility of the physician to drive a proper use of second-generation biosimilars into clinical practice, in accordance with guidelines issued by scientific societies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Healing and coping with life within challenges of spiritual insecurity ...

African Journals Online (AJOL)

Spiritual insecurity among African Christians is a huge challenge. The insecurity among other things arises from African people's former traditional African ancestral world view of ancestral veneration. The ancestors promote or hinder African Christians' reliance on Christ because they have presupposedly acquired the ...

Challenges of attracting private capital investments in the Russian power sector

Energy Technology Data Exchange (ETDEWEB)

Kiss, Peter; Sagodi, Attila

2010-09-15

The level of investment required by the Russian power sector by 2020 are expected to be in the range of USD 500-550 billion. It is of vital importance that Russia outlines an appropriate regulatory regime for its energy market that attracts foreign investors and combats corruption. The most important challenges determining the long term development of the country's power sector are skills development, regulatory effectiveness, corporate governance, and assurance regarding private investments.

Anomalous Posterior Intercostal Arterial Trunk Arising From the Abdominal Aorta

Energy Technology Data Exchange (ETDEWEB)

Jie, Bing, E-mail: jbshh@163.com; Yu, Dong, E-mail: yudong-mail@126.com; Jiang, Sen, E-mail: jasfly77@vip.163.com [Tongji University School of Medicine, Department of Radiology, Shanghai Pulmonary Hospital (China)

2016-04-15

A common trunk of the ipsilateral posterior intercostal artery (PIA) arising from the thoracic aorta is usually an anatomical variation. However, a common trunk of bilateral posterior intercostal arterial trunk (PIAT) arising from the abdominal aorta is rare. It is important to recognize this anatomical variation of PIA when performing interventional radiological procedures. We present a rare case of an anomalous PIAT that originated from the abdominal aorta in a patient with hemoptysis caused by tuberculosis sequelae. Bilateral 4th to 11th PIAs arose from a common trunk and the trunk arising from the posterior aspect of the abdominal aorta at the level of T12/L1 intervertebral space. The pathological right 4th and 5th PIAs and bronchial arteries were embolized. Hemoptysis has been controlled for 3 months.

Biodiversity maintenance in food webs with regulatory environmental feedbacks.

Science.gov (United States)

Bagdassarian, Carey K; Dunham, Amy E; Brown, Christopher G; Rauscher, Daniel

2007-04-21

Although the food web is one of the most fundamental and oldest concepts in ecology, elucidating the strategies and structures by which natural communities of species persist remains a challenge to empirical and theoretical ecologists. We show that simple regulatory feedbacks between autotrophs and their environment when embedded within complex and realistic food-web models enhance biodiversity. The food webs are generated through the niche-model algorithm and coupled with predator-prey dynamics, with and without environmental feedbacks at the autotroph level. With high probability and especially at lower, more realistic connectance levels, regulatory environmental feedbacks result in fewer species extinctions, that is, in increased species persistence. These same feedback couplings, however, also sensitize food webs to environmental stresses leading to abrupt collapses in biodiversity with increased forcing. Feedback interactions between species and their material environments anchor food-web persistence, adding another dimension to biodiversity conservation. We suggest that the regulatory features of two natural systems, deep-sea tubeworms with their microbial consortia and a soil ecosystem manifesting adaptive homeostatic changes, can be embedded within niche-model food-web dynamics.

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

Science.gov (United States)

Harvey, B E; Alpert, S

1997-01-01

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

A regulatory science viewpoint on botanical–drug interactions

Directory of Open Access Journals (Sweden)

Manuela Grimstein

2018-04-01

Full Text Available There is a continued predisposition of concurrent use of drugs and botanical products. Consumers often self-administer botanical products without informing their health care providers. The perceived safety of botanical products with lack of knowledge of the interaction potential poses a challenge for providers and both efficacy and safety concerns for patients. Botanical–drug combinations can produce untoward effects when botanical constituents modulate drug metabolizing enzymes and/or transporters impacting the systemic or tissue exposure of concomitant drugs. Examples of pertinent scientific literature evaluating the interaction potential of commonly used botanicals in the US are discussed. Current methodologies that can be applied to advance our efforts in predicting drug interaction liability is presented. This review also highlights the regulatory science viewpoint on botanical–drug interactions and labeling implications. Keywords: Drug interaction, Botanical product, St. John's wort, Fruit juices, Regulatory science

Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations.

Science.gov (United States)

Lysaght, Tamra; Kerridge, Ian H; Sipp, Douglas; Porter, Gerard; Capps, Benjamin J

2017-06-01

Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts. We find that while there are many subtle technical differences in how these regulations are implemented, they are sufficiently similar that it is difficult to explain why these practices appear more prevalent in some countries and not in others. We conclude with suggestions for how international governance frameworks might be improved to discourage the exploitation of vulnerable patient populations while enabling innovation in the clinical application of cellular therapies.

Multi-objective convex programming problem arising in multivariate ...

African Journals Online (AJOL)

user

Multi-objective convex programming problem arising in ... However, although the consideration of multiple objectives may seem a novel concept, virtually any nontrivial ..... Solving multiobjective programming problems by discrete optimization.

MYC Amplification in Angiosarcoma Arising from an Arteriovenous Graft Site

Directory of Open Access Journals (Sweden)

Kristen M. Paral

2015-01-01

Full Text Available Angiosarcoma arising in association with an arteriovenous graft (AVG or fistula is a unique clinicopathologic scenario that appears to be gaining recognition in the literature. Among reported cases, none has described high-level MYC gene amplification, a genetic aberration that is increasingly unifying the various clinicopathologic subdivisions of angiosarcoma. We therefore report the MYC gene status in a case of angiosarcoma arising at an AVG site.

Manufacturing a Better Planet: Challenges Arising from the Gap between the Best Intentions and Social Realities

Directory of Open Access Journals (Sweden)

Darrin Durant

2018-05-01

Full Text Available With rising concerns about the social and environmental impacts of industrial and manufacturing waste, scientists and engineers have sought solutions to the burdens of waste which do not simply involve burying, burning, dumping or diluting. Our purpose here is to sketch how social science perspectives can illuminate aspects of the waste problem which are not routinely grappled with within science and engineering perspectives. We argue that if one is concerned about the burdens of waste, it is crucial to understand the way political and cultural contexts shape what happens (or does not happen in regards to reuse. We sketch some of the challenges facing green manufacturing; challenges that hinge on the gap between the best laid plans and social realities. Rather than imply green manufacturing is simply a post hoc move to hide the excesses of industrial capitalism in the green cloth of sustainability, we hope our discussion can assist those who hope to use green manufacturing as a pre-emptive move to build sustainability into industrial capitalism. We suggest that a socio-political conception of technology can bring greater depth to understandings of the industrial, political and consumer environments into which green manufacturing researchers hope to insert their efforts.

Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

Science.gov (United States)

Hall, Wayne

2017-04-01

The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

Cosmetic Surgery: Regulatory Challenges in a Global Beauty Market.

Science.gov (United States)

Griffiths, Danielle; Mullock, Alex

2017-02-28

The market for cosmetic surgery tourism is growing with an increase in people travelling abroad for cosmetic surgery. While the reasons for seeking cosmetic surgery abroad may vary the most common reason is financial, but does cheaper surgery abroad carry greater risks? We explore the risks of poorly regulated cosmetic surgery to society generally before discussing how harm might be magnified in the context of cosmetic tourism, where the demand for cheaper surgery drives the market and makes surgery accessible for increasing numbers of people. This contributes to the normalisation of surgical enhancement, creating unhealthy cultural pressure to undergo invasive and risky procedures in the name of beauty. In addressing the harms of poorly regulated surgery, a number of organisations purport to provide a register of safe and ethical plastic surgeons, yet this arguably achieves little and in the absence of improved regulation the risks are likely to grow as the global market expands to meet demand. While the evidence suggests that global regulation is needed, the paper concludes that since a global regulatory response is unlikely, more robust domestic regulation may be the best approach. While domestic regulation may increase the drive towards foreign providers it may also have a symbolic effect which will reduce this drive by making people more aware of the dangers of surgery, both to society and individual physical wellbeing.

EU risk governance of 'cloned food': regulatory uncertainty between trade and non-trade

NARCIS (Netherlands)

Weimer, M.; van Asselt, M.B.A.; Versluis, E.; Vos, E.

2013-01-01

This chapter analyzes the difficulties of creating a viable legal framework for ‘cloned food’ in the EU combining a legal perspective with insights from the interdisciplinary research on risk governance. Animal cloning offers an instructive example for the challenges of designing regulatory

NEW FORMS OF EMPLOYMENT AS CONTEMPORARY CHALLENGE FOR LABOUR LAW – THE CASE OF UBER

Directory of Open Access Journals (Sweden)

Iva Bjelinski Radić

2017-01-01

Full Text Available Recently, under the influence of rapid development of digital technologies, new flexible forms of employment have emerged, which are characterized by strong or prevalent support of information and communication technology. Online platform Uber which provides urban passenger transport services is one of the best known examples of the abovementioned changes in work organization. Taking into account that emergence of Uber has given rise to numerous controversies and set new contemporary regulatory challenges in the labour law field, the author in this paper problematizes the main labour law issues and challenges arising from Uber’s business model. The first part of the paper contains the short overview of the new forms of employment emerged under the influence of digitalisation of labour market, with the special emphasis on the model of crowd work. In the second part the author analyses the Uber’s business model. In the third part the issue of classification of Uber drivers as employees or self-employed persons is examined in detail. The following question has been considered especially from the Croatian labour law perspective – whether the key elements of an employment relationship are de facto present, and to what extent, in the contractual relationship between Uber and its drivers – partners. Finally, the author concludes with the final remarks and underlines the need to establish clear and transparent legal framework which will be suitable for development of the new forms of employment emerged under the influence of digital technologies.

Regulatory T Cells in Post-stroke Immune Homeostasis.

Science.gov (United States)

Liesz, Arthur; Kleinschnitz, Christoph

2016-08-01

The secondary neuroinflammatory response has come into focus of experimental stroke research. Immunological mechanisms after acute stroke are being investigated in the hope to identify novel and druggable pathways that contribute to secondary infarct growth after stroke. Among a variety of neuroimmunological events after acute brain ischemia, including microglial activation, brain leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have been identified as the key leukocyte subpopulation driving the neuroinflammatory response and contributing to stroke outcome. Several studies have shown that pro-inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting their invasion to the injured brain is neuroprotective. In contrast to the effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are critically involved in maintaining immune homeostasis and have been characterized as disease-limiting protective cells in several inflammatory conditions, particularly in primary inflammatory diseases of the central nervous system (CNS). However, due to the complex function of regulatory cells in immune homeostasis and disease, divergent findings have been described for the role of Treg in stroke models. Emerging evidence suggests that this discrepancy arises from potentially differing functions of Treg depending on the predominant site of action within the neurovascular unit and the surrounding inflammatory milieu. This article will provide a comprehensive review of current findings on Treg in brain ischemia models and discuss potential reasons for the observed discrepancies.

Challenges in sexual medicine

DEFF Research Database (Denmark)

Cellek, Selim; Giraldi, Annamaria

2012-01-01

The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

Empiricism Verses Rationalism: Matters Arising in Medical Practice ...

African Journals Online (AJOL)

Empiricism Verses Rationalism: Matters Arising in Medical Practice. ... AFRREV STECH: An International Journal of Science and Technology ... entirely antagonistic to one another, one favoring the senses and the other favoring the mind.

PNRA: Practically Improving Safety Culture within the Regulatory Body

International Nuclear Information System (INIS)

Bhatti, S.A.N.; Habib, M.A.

2016-01-01

The prevalence of a good safety culture is equally important for all kind of organizations involved in nuclear business including operating organizations, designers, regulator, etc., and this should be reflected through the processes and activities of these organizations. The need for inculcating safety culture into regulatory processes and practices is gradually increasing since the major nuclear accident of Fukushima, Japan. Accordingly, several international fora in last few years repeatedly highlighted the importance of prevalence of safety culture in regulatory bodies as well. The utilisation of concept of safety culture remained applicable in regulatory activities of PNRA in the form of core values. After the Fukushima accident, PNRA considered it important to check the extent of utilisation of safety culture concept in organizational activities and decided to conduct its “Safety Culture Self-Assessment (SCSA)” for presenting itself as role model in-order to endorse the fact that safety culture at regulatory authority plays an important role to influence safety culture at licenced facilities. Considering the complexity of cultural assessment starting from visual manifestations to the basic assumptions at the deeper level, PNRA decided to utilise IAEA emerging methodology for assessment of culture and then used modified IAEA normative framework (made it applicable for regulatory body) for assessing safety culture at a regulatory body. PNRA SCSA team utilised safety culture assessment tools (observations, focus groups, surveys, interviews and document analysis) for collecting cultural facts by including all level of personnel involved in different activities and functions in the organization. Different challenges were encountered during implementation of these tools which were tackled with the background of training on SCSA and with the help of experts during support missions arranged by IAEA. Before formally starting the SCSA process, pre-launch activities

Self-Regulatory Skill Among Children with and without Developmental Coordination Disorder: An Exploratory Study.

Science.gov (United States)

Sangster Jokić, Claire A; Whitebread, David

2016-11-01

Children with developmental coordination disorder (DCD) experience difficulty learning and performing everyday motor tasks due to poor motor coordination. Recent research applying a cognitive learning paradigm has argued that children with DCD have less effective cognitive and metacognitive skills with which to effectively acquire motor skills. However, there is currently limited research examining individual differences in children's use of self-regulatory and metacognitive skill during motor learning. This exploratory study aimed to compare the self-regulatory performance of children with and without DCD. Using a mixed methods approach, this study observed and compared the self-regulatory behavior of 15 children with and without DCD, aged between 7 and 9 years, during socially mediated motor practice. Observation was conducted using a quantitative coding scheme and qualitative analysis of video-recorded sessions. This paper will focus on the results of quantitative analysis, while data arising from the qualitative analysis will be used to support quantitative findings. In general, findings indicate that children with DCD exhibit less independent and more ineffective self-regulatory skill during motor learning than their typically developing peers. In addition, children with DCD rely more heavily on external support for effective regulation and are more likely to exhibit negative patterns of motivational regulation. These findings provide further support for the notion that children with DCD experience difficulty effectively self-regulating motor learning. Implications for practice and directions for future research are discussed.

Scientific and regulatory challenges in evaluating clinical trial protocols for HIV-1/AIDS vaccines - A review from a regulatory perspective.

Science.gov (United States)

Sheets, Rebecca L; Zhou, TieQun; Knezevic, Ivana

2016-03-01

Clinical development of prophylactic HIV/AIDS vaccines presents many scientific challenges that result in challenges for regulators reviewing clinical trial applications (CTAs). The World Health Organization (WHO) has the responsibility to provide technical support to these regulators. The search for an HIV/AIDS vaccine will only succeed through well-designed, -conducted and -controlled human efficacy studies reviewed and approved by regulators in countries worldwide, particularly in countries where the epidemic has hit hardest, such as in sub-Saharan Africa and Asia. This review summarizes the current candidates in development and focuses on challenges regulators face when reviewing CTAs, such as the evolving landscape of "standard of prevention," trials in adolescents, adaptive trial designs, correlates of protection and their analysis, and access to successful vaccines. There are many unknowns in the field of HIV/AIDS vaccine development and often, there is not a clear right or wrong approach because of the scientific challenges described in this review. Consequently, regulators should not feel that decisions need be made in isolation, when there are many available international collaborative efforts and opportunities to seek expert advice. The WHO provides many such opportunities and support to regulators across the globe. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles

DEFF Research Database (Denmark)

Wagner, Sebastian Alexander; Beli, Petra; Weinert, Brian Tate

2011-01-01

Post-translational modification of proteins by ubiquitin is a fundamentally important regulatory mechanism. However, proteome-wide analysis of endogenous ubiquitylation remains a challenging task, and almost always has relied on cells expressing affinity tagged ubiquitin. Here we combine single...

XcisClique: analysis of regulatory bicliques

Directory of Open Access Journals (Sweden)

Grene Ruth

2006-04-01

Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

Clinical Challenges in the Growing Medical Marijuana Field.

Science.gov (United States)

Barker, Jonathan

2018-02-02

Unique clinical challenges arise with the growing number of patients who possess medical marijuana cards. Medical marijuana patients with mental disorders can have worsening symptoms with marijuana use. Often there is sparse continuity of care between the patient and the medical marijuana practitioner. Lack of communication between the patient's treating practitioners and the practitioner who has authorized the medical marijuana can be problematic. This article is a discussion of the new clinical challenges practitioners are likely to encounter with the growing number of medical marijuana patients. [Full article available at http://rimed.org/rimedicaljournal-2018-02.asp].

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

Regulatory body core competencies: when should a regulator contract a TSO?

International Nuclear Information System (INIS)

Wieland, Patricia; Salati de Almeida, Ivan P.; Almeida, Claudio U.; Costa, Eduardo M.

2008-01-01

The main nuclear regulatory functions are authorization, safety review and assessment, inspection and enforcement and development of regulations and guides. Additionally, the following supplementary functions may be executed by the regulatory body: research and development, emergency response and international cooperation. In order to function properly, the regulatory body should also have the following support functions: general management, logistics, training, communication and information, information technology support, institutional relationship, internal controls and audits, ombudsman and legal support. Technical Support Organizations (TSOs) may assist the regulatory body in meeting the challenges in a rapid growing and changing environment. Specially when there is a temporary need for a wider technical expertise diversity, short time to finish a project or when the cost of developing and maintaining infrastructure of their own laboratories for analysis and research is too high and may deviate the focus on the regulator's mission. Decision on the 'size' of the regulatory body and on what can be contracted to a Technical Support Organization (TSO) depends on the resources and capabilities needed to fulfil the regulatory functions efficiently. It is important to establish the core competencies that must be at the regulatory body, keeping the focus on the regulatory goals and define the real need to contract a TSO, weighting the benefits and disadvantages. As a contribution to the definition of the regulatory core competencies, the paper discusses what is essential to be kept at the regulatory body and what can be delegated to a TSO; how to manage and control the work of the TSO; the cost effectiveness of contracting, sharing of tacit knowledge; how to handle eventual conflicts between the parties involved in the licensing process; contract types and risk evaluation, concerning the dependence on a TSO, eventual change of partners and the intellectual capital

Economic regulation of Canada's natural gas delivery industry : policy and regulatory principles

International Nuclear Information System (INIS)

Gormley, B.

2006-03-01

This policy paper demonstrated how restoring balance and clarity to Canada's regulatory environment will ensure the continued strength of the economy, environment, and communities. It was noted that regulatory outcomes that reflect the broad public interest can be achieved if 4 basic principles for economic regulation are pursued. These principles include strength, balance, efficiency, and clarity. In particular, this paper addressed the challenge facing Canada's natural gas delivery industry in terms of increased energy demand, tight supply, ageing infrastructure and increasing cost pressures on the energy system. It emphasized that transparent, efficient energy policy developed through informed debate can provide the foundation for a reliable, environmentally acceptable and sustainable energy future. It was suggested that immediate attention be given to rebalancing the regulatory processes that have placed short term considerations above the longer term strength of the natural gas system; improving the support for new natural gas supply development; reconsidering pricing in some energy markets where information has been distorted; and revisiting the regulatory processes that have become inefficient

Cellular schwannoma arising from sigmoid mesocolon presenting ...

African Journals Online (AJOL)

Schwannomas are a type of peripheral nerve sheath tumors with clinically indolent behavior. Though, they can occur anywhere in body, the incidence in retroperitoneum, mediastinum, and pelvis is exceedingly rare. We present a case of a 58‑year‑old female with a massive twisted tumor arising from sigmoid mesocolon.

Cellular Schwannoma Arising from Sigmoid Mesocolon Presenting ...

African Journals Online (AJOL)

Schwannomas are a type of peripheral nerve sheath tumors with clinically indolent behavior. Though, they can occur anywhere in body, the incidence in retroperitoneum, mediastinum, and pelvis is exceedingly rare. We present a case of a 58‑year‑old female with a massive twisted tumor arising from sigmoid mesocolon.

Legal framework of the environmental regulatory regime

International Nuclear Information System (INIS)

Black, D.

1992-01-01

The growing concern regarding environmental issues has presented a number of new challenges to those exploring and developing the hydrocarbon reserves located on the Newfoundland continental shelf. Not the least of these challenges is the development of new technologies in the harsh environment of the North Atlantic; in addition, these new technologies must be implemented in an existing and ever-changing regulatory regime. The legal framework of the environmental regulatory regime relating to offshore development in Canada is reviewed along with some of the more important legislation involved in regulating environmental issues in the offshore area. The legal basis for exploration, development, and management of resources located on the Newfoundland continental shelf is the Canada-Newfoundland Accord on Joint Management of Offshore Oil and Gas Resources off Newfoundland and Labrador. Administration of the Accord is the responsibility of the Canada-Newfoundland Offshore Petroleum Board. To be able to apply Canadian laws to the continental shelf, legislation was passed including the Canadian Laws Offshore Application Act as well as the Act implementing the Accord. The latter gives the Offshore Petroleum Board authority to regulate all stages involved in bringing an oil pool to production, such as granting of licenses and work authorizations. Granting of such licenses and authorizations is subject to compliance with environmental requirements, and there are provisions against certain environmental offenses such as spills. Other federal legislation applicable to the offshore includes the Canada Shipping Act and the Canadian Environmental Protection Act

Regulatory issues of natural gas distribution; Aspectos regulatorios acerca da distribuicao de gas natural

Energy Technology Data Exchange (ETDEWEB)

Leite, Fabio Augusto C.C.M.; Costa, Hirdan Katarina de M. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Faculdade de Direito

2004-07-01

In these past few years, natural gas in Brazil has arised as one of the alternatives for the energetic crisis suffered by the country. Such situation was one of the motives for its expansion, rising, after that, the importance of the regulation of its distribution. The regulation of canalized natural gas distribution can be found in the Federal Constitution, after Constitutional Amendment n. 05/95, in the article n. 25, para. 2nd, which say that belongs to the Federal States the concession or direct exercise of canalized natural gas services, now clearly classified as a public service. In order of these events, its imperative the analysis of natural gas distribution's public service, because it belongs to the Federal States. According to this situation, the study of the new regulatory function of the Administration and the tracing of action for the regulatory state agencies are the main goals of this work. As so, the present research aims to focus the reflexes from the actual dimension of natural gas distribution, specially referring to its regulatory statements, the limitations of state agencies, the National Petroleum Agency and the market where distribution belongs, and particularly the open access of new agents. (author)

Primary chondroid chordoma arising from the petrous temporal bone: a case report

Energy Technology Data Exchange (ETDEWEB)

Lee, Young Uk; Youn, Eun Kyung [Koryo General Hospital, Seoul (Korea, Republic of)

1991-01-15

Chordomas are uncommon tumors which arise from remnants of the primitive notochord. They are situated chiefly in the anterior spinal axis with a predilection for the sacrococcygeal region and the basiocciput. About 50% of chordomas are sacrococcygeal, 35% are intracranial, and 15% arise from a vertebral body. As a histologic variant of chordoma, /chondroid chordoma' was first described by Heffelfinger et al. We present a rare case of primary chondroid chordoma arising from the petrous temporal bone. To our knowledge, only two other cases of this type have been reported earlier.

Primary chondroid chordoma arising from the petrous temporal bone: a case report

International Nuclear Information System (INIS)

Lee, Young Uk; Youn, Eun Kyung

1991-01-01

Chordomas are uncommon tumors which arise from remnants of the primitive notochord. They are situated chiefly in the anterior spinal axis with a predilection for the sacrococcygeal region and the basiocciput. About 50% of chordomas are sacrococcygeal, 35% are intracranial, and 15% arise from a vertebral body. As a histologic variant of chordoma, /chondroid chordoma' was first described by Heffelfinger et al. We present a rare case of primary chondroid chordoma arising from the petrous temporal bone. To our knowledge, only two other cases of this type have been reported earlier

Regulatory Oversight of Cell and Gene Therapy Products in Canada.

Science.gov (United States)

Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

2015-01-01

Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

Simple mathematical models of gene regulatory dynamics

CERN Document Server

Mackey, Michael C; Tyran-Kamińska, Marta; Zeron, Eduardo S

2016-01-01

This is a short and self-contained introduction to the field of mathematical modeling of gene-networks in bacteria. As an entry point to the field, we focus on the analysis of simple gene-network dynamics. The notes commence with an introduction to the deterministic modeling of gene-networks, with extensive reference to applicable results coming from dynamical systems theory. The second part of the notes treats extensively several approaches to the study of gene-network dynamics in the presence of noise—either arising from low numbers of molecules involved, or due to noise external to the regulatory process. The third and final part of the notes gives a detailed treatment of three well studied and concrete examples of gene-network dynamics by considering the lactose operon, the tryptophan operon, and the lysis-lysogeny switch. The notes contain an index for easy location of particular topics as well as an extensive bibliography of the current literature. The target audience of these notes are mainly graduat...

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

Science.gov (United States)

Johnson, F Reed; Zhou, Mo

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

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

Approaches to technical and scientific support for the nuclear regulatory body in Belarus

International Nuclear Information System (INIS)

Lobacha, Dmitry J.; Teskeb, Hartmuth

2010-01-01

Approaches to technical and scientific support for the State NPP Program in Belarus are described and compared with the recommendations of the IAEA. The past infrastructure in Belarus did not have specialized technical support organization (TSO) for the nuclear regulatory body. Currently, there are two technical and scientific support centers, nominated by decrees. They are part of the NPP infrastructure and belong to the National Academy of Sciences and the Ministry of Energy. It is a challenge to establish the needed TSO capacities for the nuclear regulatory body (the Ministry for Emergency Situations) inside existing institutions of the Ministry for Emergency Situations (MES). Initially, the new technical support structure could focus on well known topics like emergency preparedness and radiation protection. The scope of work has to be extended to all major aspects of radiation and nuclear safety of the new NPP soon. National education as well as international knowledge transfer are important for that. Tasks and challenges of new technical safety institution(s) are described. (author)

The CANDU-PHW generating system waste arisings

International Nuclear Information System (INIS)

Simmons, G.R.

1979-03-01

In this report, the volume of material and level of contained radioactive nuclides are tabulated for wastes arising from four fuel cycles which might be operated in CANDU-PHW (CANada Deuterium Uranium - Pressurized Heavy Water) reactors. The data presented, based on Canadian experience and/or studies, cover the range of conditioned waste volumes which could be expected from steady-state (no growth), CANDU-PHW-powered electrical generating systems. The wastes arising from operation and decommissioning of facilities in each phase of each fuel cycle are estimated. Each fuel cycle is considered to operate in isolation with the data given in terms of quantities per gigawatt-year of electricity produced. Three of the fuel cycles for which data are presented, the natural uranium once-through cycle, the plutonium-enriched uranium cycle (plutonium recycle) and the low-burnup uranium-enriched thorium cycle (thorium and uranium recycle), were studied by INFCE WG.7 (the International Nuclear Fuel Cycle Evaluation, Working Group 7) as fuel cycles 4, 5 and 6. The high-burnup uranium-enriched thorium cycle is included for comparison. INFCE WG.7 selected many common reference parameters which are applied uniformly to all seven INFCE WG.7 reference fuel cycles in determining waste arisings. Where these parameters differ from the data of Canadian origin given in the body of this report, the INFCE WG.7 data are given in an appendix. The waste management costs associated with operation of each INFCE WG.7 reference fuel cycle were calculated and compared by the working group. An arbitrary set of costing parameters and disposal technologies was selected by the working group for application to each of the reference fuel cycles. The waste management and disposal costs for the PHW reactor fuel cycles based on these arbitrary cost parameters are given in an appendix. (author)

Squamous cell carcinoma arising within a maxillary odontogenic keratocyst: A rare occurrence

International Nuclear Information System (INIS)

Jalali, Elnaz; Tadinada, Aditya; Rengasamy, Kandasamy; Ferneini, Elie M.

2017-01-01

Squamous cell carcinoma (SCC) arising within the lining of an odontogenic keratocyst (OKC) is a rare occurrence. Although potentially locally destructive, OKC is a benign odontogenic process that typically presents with clinical and radiographic features characteristic of a benign intraosseous neoplasm. We present the clinical and radiographic features of a maxillary mass that demonstrated SCC arising from the lining of an OKC. Although the initial clinical and radiographic presentation suggested an infection or malignant neoplasm, biopsies revealed an infiltrative well-differentiated SCC contiguous with and arising from the focus of a pre-existing OKC. The patient subsequently underwent a type II hemi-maxillectomy with neoadjuvant chemoradiation. This report discusses the clinical and radiographic features associated with intraosseous malignancies, especially those arising from an otherwise benign odontogenic lesion. While the majority of OKCs are benign, the current report illustrates the potential for carcinomatous transformation within the lining of an OKC

Squamous cell carcinoma arising within a maxillary odontogenic keratocyst: A rare occurrence

Energy Technology Data Exchange (ETDEWEB)

Jalali, Elnaz [Eliray Oral and Maxillofacial Radiology Consulting Services, Miami (United States); Tadinada, Aditya; Rengasamy, Kandasamy; Ferneini, Elie M. [University of Connecticut, School of Dental Medicine, Farmington (United States)

2017-06-15

Squamous cell carcinoma (SCC) arising within the lining of an odontogenic keratocyst (OKC) is a rare occurrence. Although potentially locally destructive, OKC is a benign odontogenic process that typically presents with clinical and radiographic features characteristic of a benign intraosseous neoplasm. We present the clinical and radiographic features of a maxillary mass that demonstrated SCC arising from the lining of an OKC. Although the initial clinical and radiographic presentation suggested an infection or malignant neoplasm, biopsies revealed an infiltrative well-differentiated SCC contiguous with and arising from the focus of a pre-existing OKC. The patient subsequently underwent a type II hemi-maxillectomy with neoadjuvant chemoradiation. This report discusses the clinical and radiographic features associated with intraosseous malignancies, especially those arising from an otherwise benign odontogenic lesion. While the majority of OKCs are benign, the current report illustrates the potential for carcinomatous transformation within the lining of an OKC.

Accomplishments and challenges of the severe accident research

International Nuclear Information System (INIS)

Sehga, B.R.

1998-01-01

This paper describes the progress of the severe accident research since 1980, in terms of the accomplishments made so far and the challenges that remain. Much has been accomplished: many important safety issues have been resolved and consensus is near on some others. However, some of the previously identified safety issues remain as challenges, while some new ones have arisen due to the shift in focus from containment integrity to vessel integrity. New reactor designs have also created some new challenges. In general, the regulatory demands in new reactor designs are much stricter, thereby requiring much greater attention to the safety issues concerned with the containment design of the new large reactors

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

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

Science.gov (United States)

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

Dissection of regulatory networks that are altered in disease via differential co-expression.

Directory of Open Access Journals (Sweden)

David Amar

Full Text Available Comparing the gene-expression profiles of sick and healthy individuals can help in understanding disease. Such differential expression analysis is a well-established way to find gene sets whose expression is altered in the disease. Recent approaches to gene-expression analysis go a step further and seek differential co-expression patterns, wherein the level of co-expression of a set of genes differs markedly between disease and control samples. Such patterns can arise from a disease-related change in the regulatory mechanism governing that set of genes, and pinpoint dysfunctional regulatory networks. Here we present DICER, a new method for detecting differentially co-expressed gene sets using a novel probabilistic score for differential correlation. DICER goes beyond standard differential co-expression and detects pairs of modules showing differential co-expression. The expression profiles of genes within each module of the pair are correlated across all samples. The correlation between the two modules, however, differs markedly between the disease and normal samples. We show that DICER outperforms the state of the art in terms of significance and interpretability of the detected gene sets. Moreover, the gene sets discovered by DICER manifest regulation by disease-specific microRNA families. In a case study on Alzheimer's disease, DICER dissected biological processes and protein complexes into functional subunits that are differentially co-expressed, thereby revealing inner structures in disease regulatory networks.

Small reactors in the Canadian context: opportunities and challenges

Energy Technology Data Exchange (ETDEWEB)

Walker, R.S. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

2013-07-01

This presentation discusses the opportunities and challenges for small reactors in Canada. It concludes by suggesting that the success of small reactors in Canada will depend on a number of factors including private sector investment, access to international markets, stable, equitable and adaptable regulatory regime, public trust and technology.

A system-level model for the microbial regulatory genome.

Science.gov (United States)

Brooks, Aaron N; Reiss, David J; Allard, Antoine; Wu, Wei-Ju; Salvanha, Diego M; Plaisier, Christopher L; Chandrasekaran, Sriram; Pan, Min; Kaur, Amardeep; Baliga, Nitin S

2014-07-15

Microbes can tailor transcriptional responses to diverse environmental challenges despite having streamlined genomes and a limited number of regulators. Here, we present data-driven models that capture the dynamic interplay of the environment and genome-encoded regulatory programs of two types of prokaryotes: Escherichia coli (a bacterium) and Halobacterium salinarum (an archaeon). The models reveal how the genome-wide distributions of cis-acting gene regulatory elements and the conditional influences of transcription factors at each of those elements encode programs for eliciting a wide array of environment-specific responses. We demonstrate how these programs partition transcriptional regulation of genes within regulons and operons to re-organize gene-gene functional associations in each environment. The models capture fitness-relevant co-regulation by different transcriptional control mechanisms acting across the entire genome, to define a generalized, system-level organizing principle for prokaryotic gene regulatory networks that goes well beyond existing paradigms of gene regulation. An online resource (http://egrin2.systemsbiology.net) has been developed to facilitate multiscale exploration of conditional gene regulation in the two prokaryotes. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Occupancy statistics arising from weighted particle rearrangements

International Nuclear Information System (INIS)

Huillet, Thierry

2007-01-01

The box-occupancy distributions arising from weighted rearrangements of a particle system are investigated. In the grand-canonical ensemble, they are characterized by determinantal joint probability generating functions. For doubly non-negative weight matrices, fractional occupancy statistics, generalizing Fermi-Dirac and Bose-Einstein statistics, can be defined. A spatially extended version of these balls-in-boxes problems is investigated

ACR-1000TM Project - Licensing Opportunities and Challenges

International Nuclear Information System (INIS)

Popov, N.; Doerffer, S.; Ion, R.; Hopwood, J.

2011-01-01

Atomic Energy of Canada Limited (AECL) has developed the Advanced CANDU Reactor TM 1 1000 (ACR-1000 TM ) as an evolutionary advancement of the current CANDU 6 reactor. The ACR-1000 design has evolved from AECL's in-depth knowledge of CANDU TM systems, components, and materials, as well as the experience and feedback received from owners and operators of CANDU plants. The ACR design retains the proven strengths and features of CANDU reactors, while incorporating innovations and state-of-the-art technology. It also features major improvements in economics, inherent safety characteristics, and performance, while retaining the proven benefits of the CANDU family of nuclear power plants. To ensure that the ACR design is compliant with Canadian and international requirements, regulatory pre-project reviews of the ACR-1000 (and ACR-700 TM 1 with lower output) were conducted early in the design work. The regulatory feedback from these pre-project regulatory reviews helped AECL to better understand regulatory expectations in Canada, US and the UK, and to make further advancements and improvements in the ACR design to meet the Canadian and international regulatory requirements. This paper provides an overview of the key design features of the ACR-1000 reactor design, and summary of the pre-project reviews by those above-mentioned regulatory bodies, demonstrating opportunities and challenges in licensing process of and pointing to the importance of efficient vendor-regulator interaction. (author)

Assessing and managing regulatory risk in renewable energy: Contrasts between Canada and the United States

International Nuclear Information System (INIS)

Holburn, Guy L.F.

2012-01-01

Abstact: A challenge for energy firms when considering new investments is to balance expected financial gains against potential risks. However, while investment opportunities in different jurisdictions are often straightforward to identify, the policy or regulatory risks for investors are more difficult to accurately ascertain. Here, I provide a novel conceptual framework for how firms can assess regulatory risk that focuses on the institutional processes governing policy-making. Risks are lower – and policies will subsequently be more stable – in jurisdictions where regulatory agencies have greater autonomy from politicians and where policies are formulated through more ‘rigid’ policy-making processes. The contrasting development patterns of renewable energy policies in Ontario and Texas offer support for the framework. I further develop strategies for how firms can successfully manage regulatory risks in different types of environment. - Highlights: ► The paper provides a conceptual framework for how firms can assess regulatory risk. ► Risks are lower when regulators have greater autonomy from elected politicians. ► Risks are lower when policy-making processes are more ‘rigid’. ► Firms can strategically mitigate regulatory risk in different types of environment.

Social media and pharmacovigilance: A review of the opportunities and challenges.

Science.gov (United States)

Sloane, Richard; Osanlou, Orod; Lewis, David; Bollegala, Danushka; Maskell, Simon; Pirmohamed, Munir

2015-10-01

Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges remain to be addressed. We outline these key challenges identifying relevant current research and present possible solutions. © 2015 The British Pharmacological Society.

Applying evolutionary biology to address global challenges

Science.gov (United States)

Carroll, Scott P.; Jørgensen, Peter Søgaard; Kinnison, Michael T.; Bergstrom, Carl T.; Denison, R. Ford; Gluckman, Peter; Smith, Thomas B.; Strauss, Sharon Y.; Tabashnik, Bruce E.

2014-01-01

Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens and pests that evolve too quickly, and the second from the inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This review highlights both progress and gaps in genetic, developmental and environmental manipulations across the life sciences that either target the rate and direction of evolution, or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development. PMID:25213376

Technical challenges for dismantlement verification

International Nuclear Information System (INIS)

Olinger, C.T.; Stanbro, W.D.; Johnston, R.G.; Nakhleh, C.W.; Dreicer, J.S.

1997-01-01

In preparation for future nuclear arms reduction treaties, including any potential successor treaties to START I and II, the authors have been examining possible methods for bilateral warhead dismantlement verification. Warhead dismantlement verification raises significant challenges in the political, legal, and technical arenas. This discussion will focus on the technical issues raised by warhead arms controls. Technical complications arise from several sources. These will be discussed under the headings of warhead authentication, chain-of-custody, dismantlement verification, non-nuclear component tracking, component monitoring, and irreversibility. The authors will discuss possible technical options to address these challenges as applied to a generic dismantlement and disposition process, in the process identifying limitations and vulnerabilities. They expect that these considerations will play a large role in any future arms reduction effort and, therefore, should be addressed in a timely fashion

76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Science.gov (United States)

2011-04-19

... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

Security and Privacy in Fog Computing: Challenges

OpenAIRE

Mukherjee, Mithun; Matam, Rakesh; Shu, Lei; Maglaras, Leandros; Ferrag, Mohamed Amine; Choudhry, Nikumani; Kumar, Vikas

2017-01-01

open access article Fog computing paradigm extends the storage, networking, and computing facilities of the cloud computing toward the edge of the networks while offloading the cloud data centers and reducing service latency to the end users. However, the characteristics of fog computing arise new security and privacy challenges. The existing security and privacy measurements for cloud computing cannot be directly applied to the fog computing due to its features, such as mobility, heteroge...

Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

International Nuclear Information System (INIS)

2002-01-01

The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

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

Science.gov (United States)

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.

Twin-Peak Financial Regulatory Regime in China: A Desirability Analysis

DEFF Research Database (Denmark)

Hu, Chenchen

2015-01-01

In the past two decades, the Chinese financial markets have witnessed an unprecedented development and expansion, changing the landscape of the whole financial markets. But it has also drawn controversy with many scholars warning the negative consequences of the behemoth size and the increasing...... speed of the expansion of shadow banking activities. The banking activity expansion and the emergence of financial conglomerates have been challenging the effectiveness of the current institutional regulatory structure: the fragmented "One Bank and Three Commissions" system and the "Joint Meeting...... as a "deep context". By drawing on the Australia experience of the twin-peak reform and discussing the new ecology of the Chinese financial markets, the article attempts to answer the question of the desirability of a twin-peak regulatory regime in China....

The challenge of legitimizing spatially differentiated regulation

DEFF Research Database (Denmark)

Thorsøe, Martin Hvarregaard; Graversgaard, Morten; Noe, Egon

2017-01-01

Differentiating regulation is a promising approach to agri-environmental regulation that may potentially reduce the environmental impact of agriculture at the lowest possible costs for the farmers and society, but also possesses a number of challenges. In this article, we explore the challenges...... to the legitimacy of agri-environmental regulation that occurs when the regulatory regime changes from general regulation to differentiated regulation. The analysis is based on a case study of the implementation of the Buffer zone act in Denmark – a regulation that prevents agricultural production in a 10 (later 9......) meter fringe around selected waterbodies. We distinguish between two different ways of legitimizing: Producing knowledge and participation. We conclude that to harvest some of the obvious benefits of differentiated regulation a number of challenges must be resolved, 1) ensuring legitimacy...

Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature.

Science.gov (United States)

Reddy, Kavitha K; Hanke, C William; Tierney, Emily P

2011-08-01

Dermatofibrosarcoma protuberans (DFSP) is an uncommon tumor of the skin with high rates of local recurrence. Several reports describe a frequent history of local trauma. In one prior case, a DFSP arising in a tattoo site has been reported. Mohs micrographic surgery (MMS) has been used successfully for treatment. To present a case of dermatofibrosarcoma protuberans arising in the site of a prior and current tattoo, and treated with Mohs micrographic surgery. We present findings of a case of a DFSP arising in a tattoo and a review of Medline literature on the association between tattoos and cutaneous malignancy, and treatment of DFSP with MMS. Review of the literature confirms multiple reports of DFSP arising in sites of local trauma, as well as malignancies arising in sites of tattoos. The recurrence rate for MMS treatment of DFSP (0-6.6%) was found to be significantly lower than that for patients treated with wide local excision (13% to 95%). DFSP should be considered in the differential diagnosis of neoplasms arising within areas of tattoos. Sites of local trauma and tattoos may show predilection for benign and malignant changes and should be evaluated during regular skin exams. Review of the literature confirms MMS is an ideal treatment modality for DFSP as the tumor often extends far beyond clinical margins.

Two cases of basal cell carcinoma arising from chronic radiation dermatitis

International Nuclear Information System (INIS)

Wakamori, Takeshi; Takenaka, Hideya; Ueda, Eiichiro; Katoh, Norito; Kishimoto, Saburo

2003-01-01

A 48-year-old female and a 51-year-old male with basal cell carcinoma (BCC) arising from chronic radiation dermatitis are reviewed. They are treated with radiotherapy for hemangioma on their right cheek in their childhood. Review in the literature showed high incidence of the histological diagnosis of malignant skin tumors arising from chronic radiation dermatitis are follows: squamous cell carcinoma (SCC), BCC, sarcoma, and Bowen's disease. (author)

Challenges in licensing a sodium-cooled advanced recycling reactor

International Nuclear Information System (INIS)

Levin, Alan E.

2008-01-01

As part of the Global Nuclear Energy Partnership (GNEP), the U.S. Department of Energy (DOE) has focused on the use of sodium-cooled fast reactors (SFRs) for the destruction of minor actinides derived from used reactor fuel. This approach engenders an array of challenges with respect to the licensing of the reactor: the U.S. Nuclear Regulatory Commission (NRC) has never completed the review of an application for an operating license for a sodium-cooled reactor. Moreover, the current U.S. regulatory structure has been developed to deal almost exclusively with light-water reactor (LWR) designs. Consequently, the NRC must either (1) develop a new regulatory process for SFRs, or (2) reinterpret the existing regulations to apply them, as appropriate, to SFR designs. During the 1980s and 1990s, the NRC conducted preliminary safety assessments of the Sodium Advanced Fast Reactor (SAFR) and the Power Reactor Innovative Small Module (PRISM) designs, and in that context, began to consider how to apply LWR-based regulations to SFR designs. This paper builds on that work to consider the challenges, from the reactor designer's point of view, associated with licensing an SFR today, considering (1) the evolution of SFR designs, (2) the particular requirements of reactor designs to meet GNEP objectives, and (3) the evolution of NRC regulations since the conclusion of the SAFR and PRISM reviews. (author)

Are Some Technologies Beyond Regulatory Regimes?

Energy Technology Data Exchange (ETDEWEB)

Jones, Wendell B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kusnezov, Dimitri [National Nuclear Security Administration (NNSA), Washington, DC (United States)

2017-08-01

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. 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.

Ergonomics and sustainability – challenges from global supply chains

DEFF Research Database (Denmark)

Hasle, Peter; Jensen, Per Langaa

2012-01-01

The development of globalised supply chains is a major challenge for sustainability. For several years, there has been discussion within the profession whether and how ergonomics and human factors can play a role. Based on our research, we have identified five major challenges from global supply...... chains especially related to the social aspects of sustainability: (1) criteria for social sustainability, (2) the role of key performance indicators in the management of supply chains, (3) the constant changes in supply chains, (4) the challenge in establishing participation, and (5) the development...... of agency and regulatory mechanisms. There are obviously no clear and simple solutions to these challenges. One possible avenue for progress might lie in acquiring a greater understanding of the challenges from global supply chains and developing a strategy which combines social and long-term business...

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

International Nuclear Information System (INIS)

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

2016-01-01

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 that 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

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

Energy Technology Data Exchange (ETDEWEB)

Coleman, Justin Leigh [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kammerer, Annie M. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Whittaker, Andrew S. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-12-01

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 that 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 in 10 CFR

A primer on thermodynamic-based models for deciphering transcriptional regulatory logic.

Science.gov (United States)

Dresch, Jacqueline M; Richards, Megan; Ay, Ahmet

2013-09-01

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulatory challenges in manufacturing of pancreatic islets.

Science.gov (United States)

Linetsky, E; Ricordi, C

2008-03-01

At the present time, transplantation of pancreatic islet cells is considered an experimental therapy for a selected cohort of patients with type 1 diabetes, and is conducted under an Investigational New Drug (IND) application. Encouraging results of the Edmonton Protocol published in the year 2000 sparked a renewed interest in clinical transplantation of allogeneic islets, triggering a large number of IND applications for phase I clinical trials. Promising results reported by a number of centers since then prompted the Food and Drug Administration (FDA) to consider the possibility of licensing allogeneic islets as a therapeutic treatment for patients with type 1 diabetes. However, prior to licensure, issues such as safety, purity, efficacy, and potency of the islet product must be addressed. This is complicated by the intricate nature of pancreatic islets and limited characterization prior to transplantation. In this context, control of the manufacturing process plays a critical role in the definition of the final product. Despite significant progress made in standardization of the donor organ preservation methods, reagents used, and characterization assays performed to qualify an islet cell product, control of the isolation process remains a challenge. Within the scope of the FDA regulations, islet cells meet the definition of a biologic product, somatic cell therapy, and a drug. In addition, AABB standards that address cellular therapy products apply to manufacturing facilities accredited by this organization. Control of the source material, isolation process, and final product are critical issues that must be addressed in the context of FDA and other relevant regulations applicable to islet cell products.

Trait-level and week-level regulatory focus as a motivation to craft a job

NARCIS (Netherlands)

Petrou, P.; Demerouti, E.

2015-01-01

Purpose – The purpose of this paper is to address regulatory focus (promotion vs prevention) as a trait-level variable and a week-level variable linked to employee job crafting behaviors (i.e. seeking resources, seeking challenges and reducing demands). The authors hypothesized that while promotion

CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome.

Science.gov (United States)

Klann, Tyler S; Black, Joshua B; Chellappan, Malathi; Safi, Alexias; Song, Lingyun; Hilton, Isaac B; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

2017-06-01

Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. CRISPR-Cas9-based epigenome editing technologies have enabled precise perturbation of the activity of specific regulatory elements. Here we describe CRISPR-Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. Using dCas9 KRAB repressor and dCas9 p300 activator constructs and lentiviral single guide RNA libraries to target DNase I hypersensitive sites surrounding a gene of interest, we carried out both loss- and gain-of-function screens to identify regulatory elements for the β-globin and HER2 loci in human cells. CERES readily identified known and previously unidentified regulatory elements, some of which were dependent on cell type or direction of perturbation. This technology allows the high-throughput functional annotation of putative regulatory elements in their native chromosomal context.

Enrolling Advisers in Governing Privatised Agricultural Extension in Australia: Challenges and Opportunities for the Research, Development and Extension System

Science.gov (United States)

Paschen, Jana-Axinja; Reichelt, Nicole; King, Barbara; Ayre, Margaret; Nettle, Ruth

2017-01-01

Purpose: Current developments in the Australian agricultural research, development and extension (RD&E) system exemplify the complex governance challenges arising from the international privatisation of agricultural extension. Presenting early challenges emerging from a multi-stakeholder project aimed at stimulating the role of the private…

Regulatory guidance document

International Nuclear Information System (INIS)

1994-05-01

The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

Nano(Q)SAR: Challenges, pitfalls and perspectives.

Science.gov (United States)

Tantra, Ratna; Oksel, Ceyda; Puzyn, Tomasz; Wang, Jian; Robinson, Kenneth N; Wang, Xue Z; Ma, Cai Y; Wilkins, Terry

2015-01-01

Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure-activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data.

Preparation of safety regulatory requirements for new technology like digital system

International Nuclear Information System (INIS)

2012-01-01

The current regulatory requirements on digital instrumentation and control system have been reviewed by JNES, considering international trend discussed in DICWG of MDEP. MDEP DICWG held in OECD/NEA gives the opportunity to identify the convergence of applicable standards. The working group's activities include: identifying and prioritising the member countries' challenges, practices, and needs regarding standards and regulatory guidance on digital instrumentation and control; identifying areas of importance and needs for convergence of existing standards and guidance or development of new standards; sharing of information; and identifying common positions among the member countries for areas of particular importance and need. The DICWG drafted common positions on specific issues which are based on the existing standards, national regulatory guidance, best practices, and group inputs using an agreed process and framework. The following two general common positions are discussed and to be issued in this fiscal year. Verification and Validation throughout the life cycle of safety systems using digital computers. The Impact of Cyber Security Features on Digital I and C Safety Systems. (author)

Families of returned defence force personnel: a changing landscape of challenges.

Science.gov (United States)

Berle, David; Steel, Zachary

2015-08-01

This paper aims to identify the key challenges experienced by the families of defence force personnel following deployment. We undertook a selective review of four post-deployment challenges to the families of defence force personnel: (1) changes to relationships; (2) changes to family member roles and responsibilities; (3) adjustment of children and parenting challenges; and (4) anger, family conflict and violence. Emerging issues in the area of post-deployment adjustment are also discussed. Empirical studies of post-deployment family adjustment are lacking. Each of the reviewed challenges can contribute to psychological difficulties and precipitate contact with mental health services. The challenges faced by defence force personnel when returning from deployment arise within a family context. Clinicians should thoroughly assess these factors in families following deployment, but also recognise family strengths and resilience to these challenges. © The Royal Australian and New Zealand College of Psychiatrists 2015.

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

Science.gov (United States)

2010-03-10

... 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) and the Nuclear Regulatory Commission (NRC) will hold...

Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis.

Science.gov (United States)

Paik, E Sun; Kim, Tae Joong; Choi, Chel Hun; Kim, Byoung Gie; Bae, Duk Soo; Lee, Jeong Won

2018-03-01

The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC). This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery. Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p<0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant. CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan.

Science.gov (United States)

Delaney, Anthony P; Peake, Sandra L; Bellomo, Rinaldo; Cameron, Peter; Holdgate, Anna; Howe, Belinda; Higgins, Alisa; Presneill, Jeffrey; Webb, Steve

2013-09-01

The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis. In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies. Our statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. We reviewed the data collected by the research team as specified in the study protocol and detailed in the study case report form. We describe information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation, other related therapies and other relevant data with appropriate comparisons between groups. We define the primary, secondary and tertiary outcomes for the study, with description of the planned statistical analyses. We have developed a statistical analysis plan with a trial profile, mock-up tables and figures. We describe a plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies and adverse events. We describe the primary, secondary and tertiary outcomes with identification of subgroups to be analysed. We have developed a statistical analysis plan for the ARISE study, available in the public domain, before the completion of recruitment into the study. This will minimise analytical bias and

Technical and regulatory challenges for digital instrumentation and control and control room systems in nuclear plants

International Nuclear Information System (INIS)

Torok, R.; Naser, J.; Harris, T.; Keithline, K.

2006-01-01

There are several unsettled technical and licensing issues in the areas of instrumentation and control (I and C), human factors, and updated control room designs that need coordinated, proactive industry attention. Some of these issues are already causing protracted regulatory reviews for existing plants, and left untreated, may cause substantial delays and increased costs for new plant combined construction and operating license approvals. Both industry and the NRC will have roles in resolving the key issues and addressing them in future design efforts and regulatory reviews. Where action is needed, the industry will want to minimize costs and risks by defining industry consensus solutions with corresponding technical bases. NEI has formed a working group to coordinate industry efforts and communications with NRC staff. The working group will also help determine priorities and coordinate both new and existing plant resources. EPRI will provide technical input and guidance for the working group. In order to be able to conduct reviews in a timely fashion, the NRC will likely need to enhance and expand staff resources as existing plants are upgraded and new plant reviews become more active. The industry initiative began with a workshop sponsored by EPRI and NEI on March 28-29, 2006, which led to the creation of the NEI working group. The working group has now identified and prioritized important generic issues, established resolution paths and schedules, and identified the roles of various stakeholders including utility companies, EPRI, NEI, vendors and the NRC. Through the course of this initiative I and C issues for both existing and new plants are being addressed. This paper describes the key I and C related technical and regulatory issues and their implications for new and operating plants, and provides a status report on the efforts to resolve them. (authors)

Overcoming regulatory challenges in the development of companion diagnostics for monitoring and safety.

Science.gov (United States)

Shimazawa, Rumiko; Ikeda, Masayuki

2016-03-01

Concurrent development and co-approval of a companion diagnostic (CDx) with a corresponding drug is ideal, but often unfeasible. Because of limited exposure to a drug in clinical trials, crucial information on safety is sometimes revealed only after approval. Therefore, a CDx for monitoring/safety is often developed after approval of a corresponding drug. However, regulatory guidance is insufficient if contemporaneous development is not possible, thereby leaving plenty of opportunities for improvement with respect to pharmacovigilance and retrospective validation of the CDx. Furthermore, global harmonization of guidance on how to incorporate new scientific information from retrospective analyses of biomarkers should lead to the establishment of more evidence for the development of CDx for approved drugs.

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

2012-01-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks.

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A; Kellis, Manolis

2012-07-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein-protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level.

A regulatory view of nuclear containment on UK licensed sites

International Nuclear Information System (INIS)

Bradford, P.M.; McNair, I.J.

1997-01-01

Members of the UK regulatory body, HM Nuclear Installations Inspectorate (NII) have previously presented conference papers and official reports which have dealt separately with either reactor applications or chemical plant applications. The objective of this paper is to draw together a brief overview of the role of containment in protecting against potential radiological and related hazards, and to describe the factors which influence the NII's assessment of containment safety cases. It draws upon the NII's experience of regulating many types of nuclear facility, from those designed in the late 1940s through to the modern plants, such as Sizewell 'B' and THORP. The paper reviews the legislative and regulatory background within which the facilities exist and are operated. Finally, the paper reviews recent, ongoing and planned research in the field of containment, which has been designed to behave under challenge. (author)

Tolerogenic dendritic cells for regulatory T cell induction in man

Directory of Open Access Journals (Sweden)

Verena eRaker

2015-11-01

Full Text Available Dendritic cells are (DC highly specialized professional antigen-presenting cells (APC that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively well understood. Phase I trials have been conducted in autoimmune disease, with results that emphasize the feasibility and safety of treatments with tolerogenic DC. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of transplantation medicine and allergic and autoimmune diseases is strong. This review will give an overview on efforts and protocols to generate human tolerogenic DC with focus on IL-10-modulated DC as inducers of regulatory T cells and discuss their clinical applications and challenges faced in further developing this form of immunotherapy.

Regulatory Anatomy: How "Safety Logics" Structure European Transplant Medicine.

Science.gov (United States)

Hoeyer, Klaus

2015-07-01

This article proposes the term "safety logics" to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. Instead of evaluating whether safety is achieved, the point is to explore the types of "safety" produced through these logics as well as to consider the sometimes unintended consequences of such safety work. In fact, the EU rules have been giving rise to complaints from practitioners finding the directives problematic and inadequate. In this article, I explore the problems practitioners face and why they arise. In short, I expose the regulatory anatomy of the policy landscape.

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

Science.gov (United States)

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...

A New Wave of Vaccines for Non-Communicable Diseases: What Are the Regulatory Challenges?

Science.gov (United States)

Darrow, Jonathan J; Kesselheim, Aaron S

2015-01-01

Vaccines represent one of the greatest achievements of medicine, dramatically reducing the incidence of serious or life-threatening infectious diseases and allowing people to live longer, healthier lives. As life expectancy has increased, however, the burden of non-communicable diseases (NCDs) such as cancer, hypertension, atherosclerosis, and diabetes has increased. This shifting burden of disease has heightened the already urgent need for therapies that treat or prevent NCDs, a need that is now being met with increased efforts to develop NCD vaccines. Like traditional vaccines, NCD vaccines work by modulating the human immune system, but target cells, proteins or other molecules that are associated with the NCD in question rather than pathogens or pathogen-infected cells. Efforts are underway to develop NCD vaccines to address not only cancer and hypertension, but also addiction, obesity, asthma, arthritis, psoriasis, multiple sclerosis, and Crohn's disease, among others. NCD vaccines present an interesting challenge for the U.S. Food and Drug Administration (FDA), which is tasked with approving new treatments on the basis of efficacy and safety. Should NCD vaccines be evaluated under the same analytic frame as traditional vaccines, or that of biologic drugs? Despite the borrowed nomenclature, NCD vaccines differ in important ways from infectious disease vaccines. Because infectious disease vaccines are generally administered to healthy individuals, often children, tolerance for adverse events is low and willingness to pay is limited. It is important to have infectious disease vaccines even for rare or eradicated disease (e.g., smallpox), in the event of an outbreak. The efficacy of infectious disease vaccines is generally high, and the vaccines convey population level benefits associated with herd immunity and potential eradication. The combination of substantial population-level benefits, low willingness to pay, and low tolerance for adverse events explains the

Proceedings of a specialist meeting on regulatory approaches for the control of environmental residues containing naturally occurring radioactive material. Working material

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

Naturally occurring radionuclides are present in most material. The most common naturally occurring radionuclides in material are those of the uranium and thorium series and potassium-40. This material is commonly referred to as Naturally Occurring Radioactive Material (NORM). In some material the levels of naturally occurring radionuclides are significantly higher, to the extent that regulatory control may be required for radiation protection purposes. Regulation of NORM presents a range of new challenges for both regulators and operators. Unlike more traditional industries dealing with radionuclides, NORM industries have generally not had any radiological oversight and, for example, are not equipped for radiological monitoring. Some consumer goods containing NORM, which have not traditionally been considered as a radiological problem (such as some fertilizers), may require regulation and this may have social and economic consequences. The transport and disposal of NORM are also a concern, particularly due to the large volumes, which may need to be considered. For the majority of NORM, disposal has been by conventional means in the same way as for non-hazardous waste with no specific attention to radiological aspects. In some cases, there may be a need for intervention into existing NORM disposal sites. The International Commission on Radiological Protection (ICRP) published ICRP No. 82, Protection of the Public in Situations of Prolonged Radiation Exposure in 2000. This document provides guidance on managing residues, such as those arising from NORM industries, with potential impact on the public. However, with NORM residual waste there may be three different situations: residual waste created as the result of a past practice, residual waste created by an ongoing practice and waste which will arise from future activities. Regulation of NORM may therefore be consistent with consideration of a practice, an intervention or a combination of both. Different regulatory

Proceedings of a specialist meeting on regulatory approaches for the control of environmental residues containing naturally occurring radioactive material. Working material

International Nuclear Information System (INIS)

2005-01-01

Naturally occurring radionuclides are present in most material. The most common naturally occurring radionuclides in material are those of the uranium and thorium series and potassium-40. This material is commonly referred to as Naturally Occurring Radioactive Material (NORM). In some material the levels of naturally occurring radionuclides are significantly higher, to the extent that regulatory control may be required for radiation protection purposes. Regulation of NORM presents a range of new challenges for both regulators and operators. Unlike more traditional industries dealing with radionuclides, NORM industries have generally not had any radiological oversight and, for example, are not equipped for radiological monitoring. Some consumer goods containing NORM, which have not traditionally been considered as a radiological problem (such as some fertilizers), may require regulation and this may have social and economic consequences. The transport and disposal of NORM are also a concern, particularly due to the large volumes, which may need to be considered. For the majority of NORM, disposal has been by conventional means in the same way as for non-hazardous waste with no specific attention to radiological aspects. In some cases, there may be a need for intervention into existing NORM disposal sites. The International Commission on Radiological Protection (ICRP) published ICRP No. 82, Protection of the Public in Situations of Prolonged Radiation Exposure in 2000. This document provides guidance on managing residues, such as those arising from NORM industries, with potential impact on the public. However, with NORM residual waste there may be three different situations: residual waste created as the result of a past practice, residual waste created by an ongoing practice and waste which will arise from future activities. Regulation of NORM may therefore be consistent with consideration of a practice, an intervention or a combination of both. Different regulatory

Lower Limb Injuries Arising From Motorcycle Crashes | Kortor ...

African Journals Online (AJOL)

Background: Motorcycle accidents are the second most common cause of road traffic accidents in both developing and developed countries. In this study we aim to look at the pattern and characteristics of lower limb injuries arising from motorcycle accidents and evaluate early outcome of treatment. Methods: All the patients ...

On time-dependent diffusion coefficients arising from stochastic processes with memory

Science.gov (United States)

Carpio-Bernido, M. Victoria; Barredo, Wilson I.; Bernido, Christopher C.

2017-08-01

Time-dependent diffusion coefficients arise from anomalous diffusion encountered in many physical systems such as protein transport in cells. We compare these coefficients with those arising from analysis of stochastic processes with memory that go beyond fractional Brownian motion. Facilitated by the Hida white noise functional integral approach, diffusion propagators or probability density functions (pdf) are obtained and shown to be solutions of modified diffusion equations with time-dependent diffusion coefficients. This should be useful in the study of complex transport processes.

Squamous cell carcinoma arising in previously burned or irradiated skin

International Nuclear Information System (INIS)

Edwards, M.J.; Hirsch, R.M.; Broadwater, J.R.; Netscher, D.T.; Ames, F.C.

1989-01-01

Squamous cell carcinoma (SCC) arising in previously burned or irradiated skin was reviewed in 66 patients treated between 1944 and 1986. Healing of the initial injury was complicated in 70% of patients. Mean interval from initial injury to diagnosis of SCC was 37 years. The overwhelming majority of patients presented with a chronic intractable ulcer in previously injured skin. The regional relapse rate after surgical excision was very high, 58% of all patients. Predominant patterns of recurrence were in local skin and regional lymph nodes (93% of recurrences). Survival rates at 5, 10, and 20 years were 52%, 34%, and 23%, respectively. Five-year survival rates in previously burned and irradiated patients were not significantly different (53% and 50%, respectively). This review, one of the largest reported series, better defines SCC arising in previously burned or irradiated skin as a locally aggressive disease that is distinct from SCC arising in sunlight-damaged skin. An increased awareness of the significance of chronic ulceration in scar tissue may allow earlier diagnosis. Regional disease control and survival depend on surgical resection of all known disease and may require radical lymph node dissection or amputation

Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

Science.gov (United States)

Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

2015-12-01

Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Regulatory monitoring systems of fortified salt and wheat flour in selected ASEAN countries.

Science.gov (United States)

van den Wijngaart, Annoek; Bégin, France; Codling, Karen; Randall, Philip; Johnson, Quentin W

2013-06-01

Considerable efforts have been made over the past decade to address vitamin and mineral deficiencies. An increasing number of countries in the Association of Southeast Asian Nations (ASEAN) are adopting mandatory food fortification as one of the primary strategies to overcome these deficiencies. Experience shows that fortified foods can reach large parts of the population, including the poor, if the fortification is done on a mandatory rather than a voluntary basis and if the food vehicle is widely consumed. To review the importance of regulatory monitoring as an essential component of food fortification efforts in selected ASEAN countries, with special focus on the available information on regulatory monitoring systems for iodized salt and fortified wheat flour. The role of regulatory monitoring in strengthening food fortification programs was discussed during a joint regional meeting of the World Health Organization, UNICEF, the Flour Fortification Initiative, the Global Alliance for Improved Nutrition, the Micronutrient Initiative, and the World Bank on regulatory monitoring of salt and wheat flour fortification programs in Asia, which took place in Manila, Philippines, on 27-29 September 2011. This paper reviews the regulatory monitoring systems of selected ASEAN countries that participated in this meeting. Problems and challenges in regulatory monitoring systems for iodized salt and fortified wheat flour in selected ASEAN countries are identified, and a description of the role of regulatory monitoring in strengthening food fortification initiatives, particularly of salt and flour, and highlights of areas for improvement are presented. Regulatory monitoring consists of monitoring activities conducted at the production level, at customs warehouses, and at retail stores by concerned regulatory authorities, and at the production level by producers themselves, as part of quality control and assurance efforts. Unless there are appropriate enforcement and quality

Regulatory aspects of management of change - Summary and conclusions

International Nuclear Information System (INIS)

2002-01-01

Nuclear licensees are increasingly required to adapt to a more challenging commercial environment as moves to de-regulate electricity markets gather pace. One of the costs that is often perceived as being amenable to control is staffing, and hence there is significant exploration of new strategies for managing staffing levels. This report presents the outputs from a Workshop convened by the Special Experts' Group in Human and Organisational Factors (SEGHOF) of the Committee for the Safety of Nuclear Installations (CSNI) and organised by the UK Nuclear Installations Inspectorate (NII). The purpose of the workshop was to facilitate the exchange of views on, and approaches towards, the regulation of organisational change. The major risks associated with organisational change were discussed, and a range of regulatory challenges was identified for detailed discussion. There was agreement that the licensee must retain the responsibility to manage its own business but that organisational issues should be subject to regulatory scrutiny if they have the potential to impact on safety. The regulator should be able to demonstrate an approach to oversight of organisational change which is valid, transparent and consistent, and should inform the licensee of its expectations in terms of information supplied, communication and timing. The workshop confirmed that there is significant agreement between regulators concerning the need for licensees to put in place arrangements to manage organisational change. There was also broad consensus on what should constitute the elements of a licensee's management of change process. Differing views were evident about the balance between regulatory scrutiny of the process, as opposed to the outcomes of change, which largely represents differing regulatory regimes and philosophies. However, it was acknowledged that the regulator must be capable of taking an early view of the adequacy of proposed changes, rather than monitoring outcomes alone

Solitary osteochondroma arising in lumbar spinous process: Case report

Directory of Open Access Journals (Sweden)

Khaled Hadhri

2016-12-01

Full Text Available Solitary osteochondromas rarely occur in the axial skeleton. Those tumors mostly arise on the posterior elements of the cervical column causing various symptoms especially when developing within the spinal canal. Exophytic lumbar variety is uncommon presenting with palpable mass or spinal deformity. We report a 20-year-old man presenting with a solid painless mass at the lower lumbar region. Radiological examinations revealed an exophytic lesion arising in the third lumbar spinous process appearing to be a solitary osteochondroma. The lesion was treated by en-bloc resection; histopathological examination confirmed the diagnosis of osteochondroma with no evidence of recurrence at the end of 2-year follow up.

Risk-based regulation: Challenges and opportunities

International Nuclear Information System (INIS)

Bari, R.A.

1995-01-01

Over the last twenty years, man has witnessed a gradual but steady movement toward increased usage of risk-based methods and results in the regulatory process. The ''risk perspective'' as a supportive view to existing (non-risk-based or deterministic) information used in decision making has a firm foothold now in most countries that regulate nuclear power. Furthermore, in the areas outside the nuclear power field, such as health risk assessment, risk-based information is used increasingly to make decisions on potential impacts of chemical, biological, and radiological exposures. Some of the principal concepts and issues that are pertinent to risk-based regulation are reviewed. There is a growing interest in most countries in the use of risk-based methods and results to facilitate decision-making associated with regulatory processes. A summary is presented of the challenges and opportunities related to expanded use of risk-based regulation

Giant lipoma arising from deep lobe of the parotid gland

Directory of Open Access Journals (Sweden)

Hsu Ying-Che

2006-06-01

Full Text Available Abstract Background Lipomas are common benign soft tissue neoplasms but they are found very rarely in the deep lobe of parotid gland. Surgical intervention in these tumors is challenging because of the proximity of the facial nerve, and thus knowledge of the anatomy and meticulous surgical technique are essential. Case presentation A 71-year-old female presented with a large asymptomatic mass, which had occupied the left facial area for over the past fifteen years, and she requested surgical excision for a cosmetically better facial appearance. The computed tomography (CT scan showed a well-defined giant lipoma arising from the left deep parotid gland. The lipoma was successfully enucleated after full exposure and mobilization of the overlying facial nerve branches. The surgical specimen measured 9 × 6 cm in size, and histopathology revealed fibrolipoma. The patient experienced an uneventful recovery, with a satisfying facial contour and intact facial nerve function. Conclusion Giant lipomas involving the deep parotid lobe are extremely rare. The high-resolution CT scan provides an accurate and cost-effective preoperative investigative method. Surgical management of deep lobe lipoma should be performed by experienced surgeons due to the need for meticulous dissection of the facial nerve branches. Superficial parotidectomy before deep lobe lipoma removal may be unnecessary in selected cases because preservation of the superficial lobe may contribute to a better aesthetic and functional result.

Clinical Research Environment in India: Challenges and Proposed Solutions.

Science.gov (United States)

Burt, Tal; Sharma, Pooja; Dhillon, Savita; Manchanda, Mukul; Mittal, Sanjay; Trehan, Naresh

2014-11-01

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005-2013, phase-2 trials grew by (+) 19.8% CAGR from 2005-2009 and contracted by (-) 12.6% CAGR from 2009-2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005-2010 and contracted by (-) 28.8% CAGR from 2010-2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India.

Trends and impact of prudence challenges on operating nuclear plants

International Nuclear Information System (INIS)

Hoke, J.R. II

1989-01-01

Although the concept and standard for prudence associated with capital investments were first defined by U.S. Supreme Court Justice Brandeis in 1923, prudence reviews have become a growing phenomenon within the electric utility industry over the past decade. These examinations were primarily initiated by state public utilities commissions (PUCs) in response to public and political pressure in the evaluation of delays, cancellations, and cost overruns associated with large nuclear construction projects. The early application of the prudence standard was intended to be, not so much a part of the normal means of regulatory oversight, but a specific review of the management process that could not be adequately addressed within the existing regulatory framework. Since these initial construction reviews, however, the regulators have found the prudence examination to be an effective regulatory tool to evaluate other utility functions, operations, and projects. The broadening in application and scope of these reviews has introduced a new and growing dimension of concern for utility management. The primary target for prudence challenges has been the utility's decision-making process, which typically has not been well defined or documented. This paper briefly presents the trends and issues of prudence within the nuclear industry to date, the form and focus of future examinations, and the strategic measures to prepare for these preemptive challenges

Regulatory activities; Actividades regulatorias

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

Regulating the path from legacy recognition, through recovery to release from regulatory control.

Science.gov (United States)

Sneve, Malgorzata Karpow; Smith, Graham

2015-04-01

Past development of processes and technologies using radioactive material led to construction of many facilities worldwide. Some of these facilities were built and operated before the regulatory infrastructure was in place to ensure adequate control of radioactive material during operation and decommissioning. In other cases, controls were in place but did not meet modern standards, leading to what is now considered to have been inadequate control. Accidents and other events have occurred resulting in loss of control of radioactive material and unplanned releases to the environment. The legacy from these circumstances is that many countries have areas or facilities at which abnormal radiation conditions exist at levels that give rise to concerns about environmental and human health of potential interest to regulatory authorities. Regulation of these legacy situations is complex. This paper examines the regulatory challenges associated with such legacy management and brings forward suggestions for finding the path from: legacy recognition; implementation, as necessary, of urgent mitigation measures; development of a longer-term management strategy, through to release from regulatory control. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

2010-06-15

Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

Regulatory relevant and reliable methods and data for determining the environmental fate of manufactured nanomaterials

DEFF Research Database (Denmark)

Baun, Anders; Sayre, Phil; Steinhäuser, Klaus Günter

2017-01-01

The widespread use of manufactured nanomaterials (MN) increases the need for describing and predicting their environmental fate and behaviour. A number of recent reviews have addressed the scientific challenges in disclosing the governing processes for the environmental fate and behaviour of MNs,...... data. Gaps do however exist in test methods for environmental fate, such as methods to estimate heteroagglomeration and the tendency for MNs to transform in the environment.......The widespread use of manufactured nanomaterials (MN) increases the need for describing and predicting their environmental fate and behaviour. A number of recent reviews have addressed the scientific challenges in disclosing the governing processes for the environmental fate and behaviour of MNs......, however there has been less focus on the regulatory adequacy of the data available for MN. The aim of this paper is therefore to review data, testing protocols and guidance papers which describe the environmental fate and behaviour of MN with a focus on their regulatory reliability and relevance. Given...

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

Energy Technology Data Exchange (ETDEWEB)

Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Miller, John [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sigrin, Ben [National Renewable Energy Lab. (NREL), Golden, CO (United States); Reiter, Emerson [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cory, Karlynn [National Renewable Energy Lab. (NREL), Golden, CO (United States); McLaren, Joyce [National Renewable Energy Lab. (NREL), Golden, CO (United States); Seel, Joachim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, Naim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-05-01

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 retail 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.

Assessing Biobehavioural Self-Regulation and Coregulation in Early Childhood: The Parent-Child Challenge Task.

Science.gov (United States)

Lunkenheimer, Erika; Kemp, Christine J; Lucas-Thompson, Rachel G; Cole, Pamela M; Albrecht, Erin C

2017-01-01

Researchers have argued for more dynamic and contextually relevant measures of regulatory processes in interpersonal interactions. In response, we introduce and examine the effectiveness of a new task, the Parent-Child Challenge Task, designed to assess the self-regulation and coregulation of affect, goal-directed behavior, and physiology in parents and their preschoolers in response to an experimental perturbation. Concurrent and predictive validity was examined via relations with children's externalizing behaviors. Mothers used only their words to guide their 3-year-old children to complete increasingly difficult puzzles in order to win a prize ( N = 96). A challenge condition was initiated mid-way through the task with a newly introduced time limit. The challenge produced decreases in parental teaching and dyadic behavioral variability and increases in child negative affect and dyadic affective variability, measured by dynamic systems-based methods. Children rated lower on externalizing showed respiratory sinus arrhythmia (RSA) suppression in response to challenge, whereas those rated higher on externalizing showed RSA augmentation. Additionally, select task changes in affect, behavior, and physiology predicted teacher-rated externalizing behaviors four months later. Findings indicate the Parent-Child Challenge Task was effective in producing regulatory changes and suggest its utility in assessing biobehavioral self-regulation and coregulation in parents and their preschoolers.

Security risks arising from portable storage devices

CSIR Research Space (South Africa)

Molotsi, K

2012-10-01

Full Text Available of the security risks arising from the use of PSDs, and further provides possible security countermeasures to help organisations and users to protect their digital assets. APPROACH Literature review: ? To investigate security risks posed by PSDs... technology in the workplace. International Journal of Electronic Security and Digital Forensics. 3(1): 73?81 [3] Kim, K., Kim, E. & Hong S. (2009). Privacy information protection in portable device. Proceedings of International Conference on Convergence...

The Psychological Study of Video Game Players: Methodological Challenges and Practical Advice

Science.gov (United States)

King, Daniel; Delfabbro, Paul; Griffiths, Mark

2009-01-01

Video game playing has received increased academic interest over the last few decades, particularly with regard to the psychological understanding of addiction. Based on the many studies carried out by the authors, this paper summarises some of the methodological challenges which may arise when studying video game players, including obstacles…

Small-Scale Design Experiments as Working Space for Larger Mobile Communication Challenges

Science.gov (United States)

Lowe, Sarah; Stuedahl, Dagny

2014-01-01

In this paper, a design experiment using Instagram as a cultural probe is submitted as a method for analyzing the challenges that arise when considering the implementation of social media within a distributed communication space. It outlines how small, iterative investigations can reveal deeper research questions relevant to the education of…

Discovering regulatory motifs in the Plasmodium genome using comparative genomics

OpenAIRE

Wu, Jie; Sieglaff, Douglas H.; Gervin, Joshua; Xie, Xiaohui S.

2008-01-01

Motivation: Understanding gene regulation in Plasmodium, the causative agent of malaria, is an important step in deciphering its complex life cycle as well as leading to possible new targets for therapeutic applications. Very little is known about gene regulation in Plasmodium, and in particular, few regulatory elements have been identified. Such discovery has been significantly hampered by the high A-T content of some of the genomes of Plasmodium species, as well as the challenge in associat...

Legal and Regulatory Barriers to Reverse Innovation.

Science.gov (United States)

Rowthorn, Virginia; Plum, Alexander J; Zervos, John

Reverse innovation, or the importation of new, affordable, and efficacious models to high-income countries from the developing world, has emerged as a way to improve the health care system in the United States. Reverse innovation has been identified as a key emerging trend in global health systems in part because low-resourced settings are particularly good laboratories for low-cost/high-impact innovations that are developed out of necessity. A difficult question receiving scant attention is that of legal and regulatory barriers. The objective of this paper is to understand and elucidate the legal barriers faced by innovators bringing health interventions to the United States. Semistructured qualitative interviews were conducted with 9 key informants who have directly participated in the introduction of global health care approaches to the United States health system. A purposive sampling scheme was employed to identify participants. Phone interviews were conducted over one week in July 2016 with each participant and lasted an average of 35 minutes each. Purely legal barriers included questions surrounding tort liability, standard of care, and concerns around patient-administered self-care. Regulatory burdens included issues of international medical licensure, reimbursement, and task shifting and scope of work challenges among nonprofessionals (e.g. community health workers). Finally, perceived (i.e. not realized or experienced) legal and regulatory barriers to innovative modalities served as disincentives to bringing products or services developed outside of the United States to the United States market. Conflicting interests within the health care system, safety concerns, and little value placed on low-cost interventions inhibit innovation. Legal and regulatory barriers rank among, and contribute to, an anti-innovation atmosphere in healthcare for domestic and reverse innovators alike. Reverse innovation should be fostered through the thoughtful development of

Challenges in Regulating Radiation Sources and Radioactive Waste in Nigeria

International Nuclear Information System (INIS)

Ngwakwe, C.

2016-01-01

Identifying challenges that hamper the efficiency and efficacy of Regulatory Infrastructure (People and Processes) as regards ensuring safety & security of radiation sources and radioactive waste is a major step towards planning for improvement. In a world constantly motivated by technological advancements, there has been considerable increase in the use of new technologies incorporating radioactive sources in both medical and industrial applications due to its perceived benefits, hence changing the dynamics of regulation. This paper brings to the fore, contemporary challenges experienced by regulators in the course of regulating radiation sources and radioactive waste in Nigeria. These challenges encountered in the business of regulating radiation sources and radioactive waste in Nigeria amongst others include; knowledge gap in the use of novel technologies for industrial applications (e.g. radiotracers in oil & gas and wastewater management), inadequate collaboration with operators to ensure transparency in their operations, inadequate cooperation from other government agencies using ionizing radiation sources, lack of synergy between relevant government agencies, difficulty in establishing standard radioactive waste management facility for orphan & disused sources, and inadequate control of NORMS encountered in industrial activities (e.g. well logging, mining). Nigerian Nuclear Regulatory Authority (NNRA), the body saddled with the responsibility of regulating the use of ionizing radiation sources in Nigeria is empowered by the Nuclear Safety and Radiation Protection Act to ensure the protection of life, property, and the environment from the harmful effects of ionizing radiation, hence are not immune to the aforementioned challenges. (author)

The core to regulatory reform

International Nuclear Information System (INIS)

Partridge, J.W. Jr.

1993-01-01

Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

Common Practices of Transparency in the Nuclear Regulatory Organizations

International Nuclear Information System (INIS)

Lee, Chang Ju; Hah, Yeon Hee; Oh, Kju Myeng

2010-01-01

Along with greater access to information, particularly through the Internet, there is the increasing demand of the public for transparency, particularly in matters and decisions affecting their lives. The public demands to know more about Nuclear Regulatory Organization's (NROs) and their activities resulting in more interactions with the public to help make nuclear safety activities more understandable and transparent. As a general concept, 'transparency' means literally that something can be seen through. The definition tells us that it is, more actively, to provide the public with factual information about our activities, and to respond promptly to 'the public's right to know' about the information acquired by NROs. NROs around the world recognize the importance of openness and transparency to the success of their programs to protect public health and safety. All agree that good practice in transparency and being proactive with information help to protect against perceptions of secrecy and to instil public confidence and accountability in what they do. On the other hand, NROs face many challenges in their quest to be open and transparent with their stakeholders. government, nuclear operators, NGOs, media, our colleagues, and particularly with the general public. The most frequently identified challenge was striking the right balance between openness and security-related considerations with many responders citing the need to protect proprietary information whilst still accommodating the public's desire to be well informed. Other challenges include deciding how much transparency is needed to satisfy the public and how information, that is often highly technical and complex, can be presented in a meaningful way through the use of clear and simple language. In this paper, we summarize the survey results done by WGPC on relevant practices of NRO's flux of work concerning public communication matters. By comprehensively searching the international status, we may have

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

Science.gov (United States)

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...

75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2010-04-06

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

Architecture-based regulatory compliance argumentation

DEFF Research Database (Denmark)

Mihaylov, Boyan; Onea, Lucian; Hansen, Klaus Marius

2016-01-01

Standards and regulations are difficult to understand and map to software, which makes compliance with them challenging to argue for software products and development process. This is problematic since lack of compliance may lead to issues with security, safety, and even to economic sanctions....... An increasing number of applications (for example in healthcare) are expected to have to live up to regulatory requirements in the future, which will lead to more software development projects having to deal with such requirements. We present an approach that models regulations such that compliance arguments...... the approach on the migration of the telemedicine platform Net4Care to the cloud, where certain regulations (for example privacy) should be concerned. The approach has the potential to support simpler compliance argumentation with the eventual promise of safer and more secure applications....

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

Science.gov (United States)

2013-10-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer... 5210 (Publication of Transactions and Quotations) October 4, 2013. I. Introduction On August 15, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

Convex solutions of systems arising from Monge-Ampere equations

Directory of Open Access Journals (Sweden)

Haiyan Wang

2009-10-01

Full Text Available We establish two criteria for the existence of convex solutions to a boundary value problem for weakly coupled systems arising from the Monge-Ampère equations. We shall use fixed point theorems in a cone.

Decommissioning of Australian nuclear facilities - a regulatory perspective

International Nuclear Information System (INIS)

Diamond, T.V.; Mabbott, P.E.; Lawrence, B.R.

2000-01-01

Decommissioning has been a key political, economic and technical issue for the nuclear industry in recent years as older nuclear facilities have been retired. The management of decommissioning is an important part of nuclear safety as the potential exists for occupational exposures that are several times those expected during normal operation. It involves pre-planning and preparatory measures, procedures and instructions, technical and safety assessments, technology for handling large volumes of radioactive material, cost analyses, and a complex decision process. A challenge for the Commonwealth Government regulatory body, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), is to allow the Commonwealth entities that operate nuclear facilities ample freedom to address the above, at the same time ensuring that international best practice is invoked to ensure safety. Accordingly, ARPANSA has prepared a regulatory guideline, first drafted by the Nuclear Safety Bureau in March 1997, that documents the process and the criteria that it uses when assessing an application from an operating organisation for a decommissioning licence. Copyright (2000) Australasian Radiation Protection Society Inc

Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists

Science.gov (United States)

Remick, Amera K.; Catlin, Natasha R.; Quist, Erin M.; Steinbach, Thomas J.; Dixon, Darlene

2015-01-01

The Society of Toxicologic Pathology (STP) Education Committee and the STP Reproductive Special Interest Group held a North Carolina regional meeting entitled, “Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists” on March 13, 2015, at the National Institute of Environmental Health Sciences/National Toxicology Program in Research Triangle Park, North Carolina. The purpose of this regional meeting was to familiarize attendees with the topic of juvenile toxicity testing and discuss its relevance to clinical pediatric medicine, regulatory perspectives, challenges of appropriate study design confronted by toxicologists, and challenges of histopathologic examination and interpretation of juvenile tissues faced by pathologists. The 1-day meeting was a success with over 60 attendees representing industry, government, research organizations, and academia. PMID:26220944

Effects arising from charged particles overcoming of the light velocity barrier

International Nuclear Information System (INIS)

Afanas'ev, G.N.; Eliseev, S.M.; Stepanovskij, Yu.P.

1997-01-01

The effects arising from accelerated and decelerated motion of the charged point particle inside the medium are studied. It is shown explicitly that in addition to the Bremsstrahlung and Cherenkov shock wave, the electromagnetic shock wave arising from the charge overcoming the light velocity in the medium should be observed. This shock wave has the same singularity as the Cherenkov one and, therefore, it is more singular than the Bremsstrahlung shock wave. The space-time regions where these shock waves exist and conditions under which they appear are determined

Adenocarcinomas arising from primary retroperitoneal mature teratomas: CT and MR imaging

International Nuclear Information System (INIS)

Wang, Li-Jen; Wong, Yon-Cheong; Chu, Sheng-Hsien; Ng, Kwai-Fong

2002-01-01

An adenocarcinoma arising from mature teratoma is one form of teratoma with malignant transformation. It is extremely rare but highly malignant. The authors report two patients with adenocarcinomas arising from primary retroperitoneal teratomas. The CT and MRI findings of the tumors are presented with emphasis on imaging features implying the presence of malignant transformation and differing from those of pure benign mature teratoma. Correct diagnosis of the presence of malignant transformation from a benign mature teratoma can be made as early as possible by awareness of the imaging features. (orig.)

75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2010-04-26

... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

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

Science.gov (United States)

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.

Ecknomic benefits arising from the Canadian nuclear industry

International Nuclear Information System (INIS)

1982-03-01

This document is a collection of surveys of the Canadian nuclear industry, with forecasts covering a number of possible scenarios. Topics covered include uranium mining and processing; economic benefits arising from the design, manufacture and construction of CANDU generating stations; employment and economic activity in the Canadian nqclear industry; and an overview of the remainder of the industry

Session Introduction: Challenges of Pattern Recognition in Biomedical Data.

Science.gov (United States)

Verma, Shefali Setia; Verma, Anurag; Basile, Anna Okula; Bishop, Marta-Byrska; Darabos, Christian

2018-01-01

The analysis of large biomedical data often presents with various challenges related to not just the size of the data, but also to data quality issues such as heterogeneity, multidimensionality, noisiness, and incompleteness of the data. The data-intensive nature of computational genomics problems in biomedical informatics warrants the development and use of massive computer infrastructure and advanced software tools and platforms, including but not limited to the use of cloud computing. Our session aims to address these challenges in handling big data for designing a study, performing analysis, and interpreting outcomes of these analyses. These challenges have been prevalent in many studies including those which focus on the identification of novel genetic variant-phenotype associations using data from sources like Electronic Health Records (EHRs) or multi-omic data. One of the biggest challenges to focus on is the imperfect nature of the biomedical data where a lot of noise and sparseness is observed. In our session, we will present research articles that can help in identifying innovative ways to recognize and overcome newly arising challenges associated with pattern recognition in biomedical data.

Alternatives to animal experimentation: The regulatory background

International Nuclear Information System (INIS)

Garthoff, Bernward

2005-01-01

The framework, in which alternatives to animal experiments can be developed, standardized, respectively formally validated, has to be seen in a global context. The ever increasing demand of testing for hazard and risk assessment in health and environment, exemplified by the EU REACH program, subsequently triggers laboratory animal testing. This holds especially true, if no valid alternative methods agreed to by the regulatory authorities and the scientific community are available. At least for regulatory toxicity testing, the global frame and network are given by institutions such as OECD, ICH, and alike. However, due to the necessity of global consent of states, organizations, and stakeholders, the time gap between availability of a novel alternative test method and its final acceptance by authorities and implementation thereafter is widening. The lack of new technologies or opportunities for alternative method application such as, for example, the broad use of transgenic animals for refinement of existing tests, adds to the problem. The bare existence of certain in vivo tests increases also the gap between public demands for testing versus availability of alternative tests. Industries operating on a worldwide basis support the alternative test development in their respective area of research and operational business. However, a more coordinating approach such as that of the ecopa-organization (European Consensus Platform on Alternatives) is needed to exploit the existing possibilities within the current regulatory framework. This will speed up the process of acceptance and challenge the political worldto feel responsible for the sequels of their demanding more testing, that is, by funding alternative method development in academia and industry

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

Directory of Open Access Journals (Sweden)

Shuchi eSmita

2015-12-01

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

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

Science.gov (United States)

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...

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

Science.gov (United States)

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...

76 FR 21084 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2011-04-14

... Securities April 8, 2011. I. Introduction On March 3, 2011, the Financial Industry Regulatory Authority, Inc... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64283; File No. SR-FINRA-2011-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer...

Transoral videolaryngoscopic surgery for papillary carcinoma arising in lingual thyroid.

Science.gov (United States)

Mogi, Chisato; Shinomiya, Hirotaka; Fujii, Natsumi; Tsuruta, Tomoyuki; Morita, Naruhiko; Furukawa, Tatsuya; Teshima, Masanori; Kanzawa, Maki; Hirokawa, Mitsuyoshi; Otsuki, Naoki; Nibu, Ken-Ichi

2018-05-15

Carcinoma arising in lingual thyroid is an extremely rare entity accounting for only 1% of all reported ectopic thyroids. Here, we report a case of carcinoma arising in lingual thyroid, which has been successfully managed by transoral resection and bilateral neck dissections. A lingual mass 4-cm in diameter with calcification was incidentally detected by computed tomography at medical check-up. No thyroid tissue was observed in normal position. Ultrasound examination showed bilateral multiple lymphadenopathies. Fine needle aspiration biopsy from lymph node in his right neck was diagnosed as Class III and thyroglobulin level of the specimen was 459ng/ml. Due to the difficulty in performing FNA of the lingual masses, right neck dissection was performed in advance for diagnostic purpose. Pathological examination showed existence of large and small follicular thyroid tissues in several lymph nodes, suggesting lymph node metastasis from thyroid carcinoma. Two months after the initial surgery, video-assisted transoral resection of lingual thyroid with simultaneous left neck dissection was performed. Postoperative course was uneventful. Papillary carcinoma was found in the lingual thyroid and thyroid tissues were also found in left cervical lymph nodes. Video-assisted transoral resection was useful for the treatment of thyroid cancer arising in lingual thyroid. Copyright © 2018 Elsevier B.V. All rights reserved.