The impact of biotechnology on agricultural worker safety and health.

PubMed

Shutske, J M; Jenkins, S M

2002-08-01

Biotechnology applications such as the use and production of genetically modified organisms (GMOs) have been widely promoted, adopted, and employed by agricultural producers throughout the world. Yet, little research exists that examines the implications of agricultural biotechnology on the health and safety of workers involved in agricultural production and processing. Regulatory frameworks do exist to examine key issues related to food safety and environmental protection in GMO applications. However, based on the lack of research and regulatory oversight, it would appear that the potential impact on the safety and health of workers is of limited interest. This article examines some of the known worker health and safety implications related to the use and production of GMOs using the host, agent, and environment framework. The characteristics of employers, workers, inputs, production practices, and socio-economic environments in which future agricultural workers perform various tasks is likely to change based on the research summarized here.

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

PubMed

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

2013-08-01

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

The "déjà vu effect:" evaluation of United States medical device legislation, regulation, and the Food and Drug Administration's contentious 510(k) program.

PubMed

Bauman, Jordan

2012-01-01

With the Medical Device Amendments of 1976, Congress granted FDA authority to regulate medical devices by implementing a risk-based regulatory framework. Several years prior to this legislation, the Cooper Committee reviewed the medical device regulatory landscape and uncovered weaknesses that could be detrimental to public health. However, only after several high-profile incidents involving unsafe medical devices did Congress respond with strong legislation. Since 1976, additional medical device legislative revisions have been enacted to address deficiencies highlighted by various groups representing Congress, FDA, and industry. A repetitive conclusion from these groups has been that the 510(k) program is incapable of serving as a premarket evaluation of safety and effectiveness under the existing statutory framework. However, these legislative revisions did not change the statutory framework despite these repeated findings. In 2009, CDRH convened separate groups to again review the 510(k) program. While more comprehensive than previous initiatives, the observed deficiencies and the proposed recommendations are remarkably similar to those identified by their predecessors. This cyclical review of the medical device regulatory landscape whereby the same observations and recommendations are repeated yet the output of such review does not yield major legislative revision of the existing statutory framework can be described as the "déjà vu effect." This will continue unless Congress enacts legislation that implements a new statutory framework with a different standard other than substantial equivalence. In the past, Congress has implemented major legislation only after a public health crisis. Hopefully this will not be the driving force in the future.

Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union.

PubMed

Beronius, Anna; Rudén, Christina; Hanberg, Annika; Håkansson, Helen

2009-11-01

In this study we have investigated how different regulatory frameworks in Europe cope with identification and risk assessment of endocrine disrupting compounds (EDCs). Four regulatory groups were selected for the investigation: existing industrial chemicals, environmental pollutants in food, pharmaceuticals and plant protection products. The legislation and guidelines for each of these groups were scrutinized and compared in detail. In addition, one recent European risk assessment document each for three identified EDCs, i.e. bisphenol A, dioxins and vinclozolin, were reviewed and compared. We found that the requirements for toxicity testing and availability and scope of risk assessment guidelines varied between the four regulatory frameworks. Also, the general principles regarding the human relevance of the mode of action identified in animal tests differed in the different risk assessments. In conclusion, there is little conformity in the risk assessment processes between these groups of chemicals. Because of the complicated nature of endocrine disruption, test methods, principles and criteria for data interpretation traditionally used might not be directly applicable to EDCs and further development of a transparent and reliable risk assessment process for this type of substances is needed.

Comparative analysis of nursing and midwifery regulatory and professional bodies' scope of practice and associated decision-making frameworks: a discussion paper.

PubMed

Kennedy, Catriona; O'Reilly, Pauline; Fealy, Gerard; Casey, Mary; Brady, Anne-Marie; McNamara, Martin; Prizeman, Geraldine; Rohde, Daniela; Hegarty, Josephine

2015-08-01

To review, discuss and compare nursing and midwifery regulatory and professional bodies' scope of practice and associated decision-making frameworks. Scope of practice in professional nursing and midwifery is an evolving process which needs to be responsive to clinical, service, societal, demographic and fiscal changes. Codes and frameworks offer a system of rules and principles by which the nursing and midwifery professions are expected to regulate members and demonstrate responsibility to society. Discussion paper. Twelve scope of practice and associated decision-making frameworks (January 2000-March 2014). Two main approaches to the regulation of the scope of practice and associated decision-making frameworks exist internationally. The first approach is policy and regulation driven and behaviour oriented. The second approach is based on notions of autonomous decision-making, professionalism and accountability. The two approaches are not mutually exclusive, but have similar elements with a different emphasis. Both approaches lack explicit recognition of the aesthetic aspects of care and patient choice, which is a fundamental principle of evidence-based practice. Nursing organizations, regulatory authorities and nurses should recognize that scope of practice and the associated responsibility for decision-making provides a very public statement about the status of nursing in a given jurisdiction. © 2015 John Wiley & Sons Ltd.

Impact of the new european paediatric regulatory framework on ethics committees: overview and perspectives.

PubMed

Altavilla, A; Manfredi, C; Baiardi, P; Dehlinger-Kremer, M; Galletti, P; Pozuelo, A Alemany; Chaplin, J; Ceci, A

2012-01-01

To evaluate the impact of the new European paediatric regulatory framework on the activities of Ethics Committees operating in Europe and to assess their involvement and interest in paediatric research. Task-force in Europe for Drug Development for the Young Network of Excellence and Relating Expectations and Needs to the Participation and Empowerment of Children in Clinical Trials project set up an inventory of Ethics Committees existing in Europe and conducted a survey on their approach to paediatric trials. Ethics Committees operating in 22 European Countries participated in this survey. Results showed a high lack of knowledge, understanding and awareness of the current European paediatric regulatory framework and a lack of involvement of Ethics Committees in paediatric research, especially in terms of training and education, demonstrated also by the decreasing number of Ethics Committees answering exhaustively to the whole questionnaire. The majority of participating Ethics Committees expressed interest in future initiatives related to paediatric research. Despite a limited knowledge and understanding of the current paediatric regulatory framework, a significant number of Ethics Committees operating in Europe show interest in initiatives related to paediatric research. Networking may be an essential tool to be used to enhance Ethics Committees role in supporting paediatric research. Any initiative should be undertaken at European level in collaboration with European Union Institutions. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Developing and applying adverse outcome pathways: What you need to know

EPA Science Inventory

Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

GeNeDA: An Open-Source Workflow for Design Automation of Gene Regulatory Networks Inspired from Microelectronics.

PubMed

Madec, Morgan; Pecheux, François; Gendrault, Yves; Rosati, Elise; Lallement, Christophe; Haiech, Jacques

2016-10-01

The topic of this article is the development of an open-source automated design framework for synthetic biology, specifically for the design of artificial gene regulatory networks based on a digital approach. In opposition to other tools, GeNeDA is an open-source online software based on existing tools used in microelectronics that have proven their efficiency over the last 30 years. The complete framework is composed of a computation core directly adapted from an Electronic Design Automation tool, input and output interfaces, a library of elementary parts that can be achieved with gene regulatory networks, and an interface with an electrical circuit simulator. Each of these modules is an extension of microelectronics tools and concepts: ODIN II, ABC, the Verilog language, SPICE simulator, and SystemC-AMS. GeNeDA is first validated on a benchmark of several combinatorial circuits. The results highlight the importance of the part library. Then, this framework is used for the design of a sequential circuit including a biological state machine.

Adapting Preclinical Benchmarks for First-in-Human Trials of Human Embryonic Stem Cell-Based Therapies.

PubMed

Barazzetti, Gaia; Hurst, Samia A; Mauron, Alexandre

2016-08-01

: As research on human embryonic stem cell (hESC)-based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory frameworks stating preclinical requirements relevant to the move to first-in-human (FIH) trials and assessed how they may be applied in the context of hESC-based interventions to best protect research participants. Our findings show that some preclinical benchmarks require rethinking (i.e., identity, purity), while others need to be specified (i.e., potency, viability), owing to the distinctive dynamic heterogeneity of hESC-based products, which increases uncertainty and persistence of safety risks and allows for limited predictions of effects in vivo. Rethinking or adaptation of how to apply preclinical benchmarks in specific cases will be required repeatedly for different hESC-based products. This process would benefit from mutual learning if researchers included these components in the description of their methods in publications. To design translational research with an eye to protecting human participants in early trials, researchers and regulators need to start their efforts at the preclinical stage. Existing regulatory frameworks for preclinical research, however, are not really adapted to this in the case of stem cell translational medicine. This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell-based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first-in-human trials in stem cell translational medicine. ©AlphaMed Press.

Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.

PubMed

Verbeken, Gilbert; Pirnay, Jean-Paul; De Vos, Daniel; Jennes, Serge; Zizi, Martin; Lavigne, Rob; Casteels, Minne; Huys, Isabelle

2012-06-01

For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

Unmanned Aircraft Hazards and their Implications for Regulation

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J.; Maddalon, Jeffrey M.; Miner, Paul S.; DeWalt, Michael P.; McCormick, G. Frank

2006-01-01

Use of unmanned aircraft systems (UASs) has been characterized as the next great step forward in the evolution of civil aviation. Indeed, UASs are in limited civil use in the United States today, and many believe that the time is rapidly approaching when they will move into the commercial marketplace, too. To make this a reality, a number of challenges must be overcome to develop the necessary regulatory framework for assuring safe operation of this special class of aircraft. This paper discusses some of what must be done to establish that framework. In particular, we examine hazards specific to the design, operation, and flight crew of UASs, and discuss implications of these hazards for existing policy and guidance. Understanding unique characteristics of UASs that pose new hazards is essential to developing a cogent argument, and the corresponding regulatory framework, for safely integrating these aircraft into civil airspace.

The European Regulatory Environment of RNA-Based Vaccines.

PubMed

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

2017-01-01

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

Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines.

PubMed

Tusé, Daniel

2011-03-01

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.

Research Participation as Work: Comparing the Perspectives of Researchers and Economically Marginalized Populations

PubMed Central

Page, Kimberly

2012-01-01

We examined the historical and regulatory framework of research with human participants in the United States, and described some possible unintended consequences of this framework in the context of paying young injection drug users for their time participating in behavioral and medical research. We drew upon our own experiences while conducting a long-running epidemiological study of hepatitis C virus infection. We found that existing ethical and regulatory framings of research participation may lead to injustices from the perspectives of research participants. We propose considering research participation as a specialized form of work and the use of community advisory boards to facilitate discussion about appropriate compensation for research participation among economically marginalized populations. PMID:22594754

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

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

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

PubMed

Maeso, Ignacio; Tena, Juan J

2016-09-01

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

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

PubMed

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

Overview of cancer vaccines

PubMed Central

Kudrin, Alex

2012-01-01

Cancer immunotherapy has seen a tremendous number of failures and only few recent regulatory successes. This is a review dedicated to determine major regulatory and developmental issues around cancer immunotherapeutics. A three pillar approach should be used in setting a development path: discovery platforms and sufficient pool of validated tumor antigens, product development strategy enabling to bring the product closer to the patient and clinical development strategy accounting for competitive landscape, treatment paradigm, technical and commercial risks. Regulatory framework existing around cancer vaccines in the EU, US, Japan and some developing countries is outlined. In addition, the review covers some specific issues on the design and conduct of clinical trials with cancer vaccines. PMID:22894970

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

Kobos, Peter Holmes; Malczynski, Leonard A.; Walker, La Tonya Nicole

People save for retirement throughout their career because it is virtually impossible to save all you’ll need in retirement the year before you retire. Similarly, without installing incremental amounts of clean fossil, renewable or transformative energy technologies throughout the coming decades, a radical and immediate change will be near impossible the year before a policy goal is set to be in place. This notion of steady installation growth over acute installations of technology to meet policy goals is the core topic of discussion for this research. This research operationalizes this notion by developing the theoretical underpinnings of regulatory and marketmore » acceptance delays by building upon the common Technology Readiness Level (TRL) framework and offers two new additions to the research community. The new and novel Regulatory Readiness Level (RRL) and Market Readiness Level (MRL) frameworks were developed. These components, collectively called the Technology, Regulatory and Market (TRM) readiness level framework allow one to build new constraints into existing Integrated Assessment Models (IAMs) to address research questions such as, ‘To meet our desired technical and policy goals, what are the factors that affect the rate we must install technology to achieve these goals in the coming decades?’« less

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

PubMed

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.

Enhancing antimicrobial stewardship by strengthening the veterinary drug regulatory framework

PubMed Central

Mehrotra, M; Li, X-Z; Ireland, MJ

2017-01-01

Antimicrobial resistance is a major and growing public health threat. Recently, Health Canada introduced multiple regulatory changes to strengthen the oversight of antimicrobial drugs for veterinary use. These changes aim specifically at increasing control over importation of veterinary drugs and active pharmaceutical ingredients, mandatory reporting of antimicrobial sales data from manufacturers, importers and compounders and facilitating access to low risk veterinary health products. Additional policy changes under existing authorities are also being made to enhance veterinary supervision of antimicrobial use and to remove production claims for food animals from labels of medically important antimicrobial drugs. These important interlinked initiatives are aimed towards enhancing antimicrobial stewardship in Canada to preserve the effectiveness of existing antimicrobials and to protect the health of Canadians. PMID:29770050

Application of adverse outcome pathways (AOPs) in human health and ecotoxicology capturing divergent consequences of conserved molecular initiating events via AOP networks

EPA Science Inventory

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

Application of Adverse Outcome Pathways (AOPs) in Human Health and Ecotoxicology Capturing Divergent Consequences of Conserved Molecular Initiating Events via AOP Networks (Presentation)

EPA Science Inventory

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

Symbiotic relationships: saviour siblings, family rights and biomedicine.

PubMed

Bennett, Belinda

2005-12-01

It is now possible to combine the use of preimplantation genetic diagnosis (PGD) and tissue matching to select an IVF embryo that will, after birth, be a compatible tissue donor for an existing individual. This article analyses the ethical issues and the regulatory frameworks that intersect around the creation of tissue compatible children.

Current limitations and recommendations to improve testing ...

EPA Pesticide Factsheets

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

Risk Assessment to Underpin Food Regulatory Decisions: An Example of Public Health Nutritional Epidemiology

PubMed Central

Baines, Janis; Cunningham, Judy; Leemhuis, Christel; Hambridge, Tracy; Mackerras, Dorothy

2011-01-01

The approach used by food regulation agencies to examine the literature and forecast the impact of possible food regulations has many similar features to the approach used in nutritional epidemiological research. We outline the Risk Analysis Framework described by FAO/WHO, in which there is formal progression from identification of the nutrient or food chemical of interest, through to describing its effect on health and then assessing whether there is a risk to the population based on dietary exposure estimates. We then discuss some important considerations for the dietary modeling component of the Framework, including several methodological issues that also exist in research nutritional epidemiology. Finally, we give several case studies that illustrate how the different methodological components are used together to inform decisions about how to manage the regulatory problem. PMID:22254081

Pharmaceuticals in the environment: scientific evidence of risks and its regulation

PubMed Central

Küster, Anette; Adler, Nicole

2014-01-01

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. PMID:25405974

Impact of illness and its treatment on workplace costs: regulatory and measurement issues.

PubMed

Greenberg, P E; Birnbaum, H G; Kessler, R C; Morgan, M; Stang, P

2001-01-01

In an attempt to document a broader spectrum of the benefits of their pharmaceutical products, drug companies increasingly seek to include productivity claims in their promotional campaigns. We describe the existing regulatory framework of the Food and Drug Administration (FDA) for considering productivity claims, distinguishing between the traditional "substantial evidence" standard and the "competent and reliable scientific evidence" standard. But the notion of competent and reliable scientific evidence may itself be problematic, even when it is the appropriate regulatory standard, because there exists no consistent measurement approach across diseases, workplaces, jobs, and worker capabilities that is widely accepted in this emerging area of health outcomes research. We examine the various measurement approaches that have been used to quantify the impact of illness and its treatment on workplace productivity, and we describe some of the shortcomings associated with each alternative. This discussion highlights the possible difficulties faced by the FDA in reviewing productivity-based promotional claims. Finally, we suggest possible strategies for furthering this field of investigation.

A Framework for Conducting Deceased Donor Research in the United States.

PubMed

Glazier, Alexandra K; Heffernan, Kate Gallin; Rodrigue, James R

2015-11-01

There are a number of regulatory barriers both perceived and real that have hampered widespread clinical research in the field of donation and transplantation. This article sets forth a framework clarifying the existing legal requirements and their application to the conduct of research on deceased donors and donor organs within the United States. Recommendations are focused on resolving some of the ambiguity surrounding deceased donor authorization for research, Health Insurance Portability and Accountability Act requirements and the role of institutional review board oversight. The successful conduct of clinical research in the field of donation and transplantation requires an understanding of these regulatory nuances as well as identification of important ethical principles to consider. Facilitation of these concepts will ultimately provide support for innovative research designed to increase the availability of organs for transplantation. Further work identifying the optimal infrastructure for overview of clinical research in the field should be given priority.

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

PubMed

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

2014-01-01

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

A synthetic biology approach to the development of transcriptional regulatory models and custom enhancer design☆,☆☆

PubMed Central

Martinez, Carlos A.; Barr, Kenneth; Kim, Ah-Ram; Reinitz, John

2013-01-01

Synthetic biology offers novel opportunities for elucidating transcriptional regulatory mechanisms and enhancer logic. Complex cis-regulatory sequences—like the ones driving expression of the Drosophila even-skipped gene—have proven difficult to design from existing knowledge, presumably due to the large number of protein-protein interactions needed to drive the correct expression patterns of genes in multicellular organisms. This work discusses two novel computational methods for the custom design of enhancers that employ a sophisticated, empirically validated transcriptional model, optimization algorithms, and synthetic biology. These synthetic elements have both utilitarian and academic value, including improving existing regulatory models as well as evolutionary questions. The first method involves the use of simulated annealing to explore the sequence space for synthetic enhancers whose expression output fit a given search criterion. The second method uses a novel optimization algorithm to find functionally accessible pathways between two enhancer sequences. These paths describe a set of mutations wherein the predicted expression pattern does not significantly vary at any point along the path. Both methods rely on a predictive mathematical framework that maps the enhancer sequence space to functional output. PMID:23732772

Investment, regulation, and uncertainty

PubMed Central

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

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2007-01-01

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

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... Nasdaq Securities within the existing DMM and SLP framework used to trade its listed securities. The... substantially similar to the Exchange's current SLP procedures in Rule 107B--NYSE Amex Equities. See proposed..., reassign one or more Nasdaq Securities to a different DMM Unit or to a different SLP or SLPs. a. Assignment...

Pharmaceuticals in the environment: scientific evidence of risks and its regulation.

PubMed

Küster, Anette; Adler, Nicole

2014-11-19

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk-benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Regulatory and clinical considerations for biosimilar oncology drugs

PubMed Central

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

2015-01-01

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

Redesigning the Regulatory Framework for Ambulatory Care Services in New York

PubMed Central

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

2014-01-01

Context While hospitals remain important centers of gravity in the health system, services are increasingly being delivered through ambulatory care. This shift to ambulatory care is giving rise to new delivery structures, such as retail clinics and urgent care centers, as well as reinventing existing ambulatory care capacity, as seen with the patient-centered medical home model and the movement toward team-based care. To protect the public's interests, oversight of ambulatory care services must keep pace with these rapid changes. With this purpose, in January 2013 the New York Public Health and Health Planning Council undertook a redesign of the regulatory framework for the state's ambulatory care services. This article describes the principles undergirding the framework as well as the regulatory recommendations themselves. Methods We explored and analyzed the regulation of ambulatory care services in New York in accordance with the available gray and peer-reviewed literature and legislative documents. The deliberations of the Public Health and Health Planning Council informed our review. Findings The vision of high-performing ambulatory care should be rooted in the Triple Aim (better health, higher-quality care, lower costs), with a particular emphasis on continuity of care for patients. There is a pressing need to better define the taxonomy of ambulatory care services. From the state government's perspective, this clarification requires better reporting from new health care entities (eg, retail clinics), connections with regional and state health information technology hubs, and coordination among state agencies. A uniform nomenclature also would improve consumers’ understanding of rights and responsibilities. Finally, the regulatory mechanisms employed—from mandatory reporting to licensure to regional planning to the certificate of need—should remain flexible and match the degree of consensus regarding the appropriate regulatory path. Conclusions Few other states have embarked on a wide-ranging assessment of their regulation of ambulatory care services. By moving toward adopting the regulatory approach described here, New York aims to balance sound oversight with pluralism and innovation in health care delivery. PMID:25492604

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

PubMed

Sorenson, Corinna; Drummond, Michael

2014-03-01

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

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

PubMed Central

SORENSON, CORINNA; DRUMMOND, MICHAEL

2014-01-01

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

An Approach for Implementation of Project Management Information Systems

NASA Astrophysics Data System (ADS)

Běrziša, Solvita; Grabis, Jānis

Project management is governed by project management methodologies, standards, and other regulatory requirements. This chapter proposes an approach for implementing and configuring project management information systems according to requirements defined by these methodologies. The approach uses a project management specification framework to describe project management methodologies in a standardized manner. This specification is used to automatically configure the project management information system by applying appropriate transformation mechanisms. Development of the standardized framework is based on analysis of typical project management concepts and process and existing XML-based representations of project management. A demonstration example of project management information system's configuration is provided.

Molecular farming on the rise--GMO regulators still walking a tightrope.

PubMed

Spök, Armin

2007-02-01

Recent increases in EU commercial and academic activities in molecular farming, and the proximity to market-stage of the first plant-made pharmaceuticals, represent a call to action for EU regulators. Drawing on the North American debate on molecular farming, it will be argued that both the rationale and the risks of molecular farming will differ significantly from those of first generation GM crops. Based on these differences, the suitability of the existing regulatory frameworks, which were developed in response to the arrival of earlier products, is discussed, and specific options for adapting the already complex EU regulatory system to cater for molecular farming are examined.

75 FR 41264 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Amendment Nos. 2 and 3, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... Exchange proposes to trade Nasdaq Securities within the existing DMM and SLP framework used to trade its... member organization will not be permitted to be registered as both the DMM Unit and an SLP for the same... Nasdaq Securities to a different DMM Unit or to a different SLP or SLPs. \\5\\ A representative of NYSE...

Regulation of xenogeneic porcine pancreatic islets.

PubMed

Arcidiacono, Judith A; Evdokimov, Evgenij; Lee, Mark H; Jones, Jeff; Rudenko, Larisa; Schneider, Bruce; Snoy, Phillip J; Wei, Cheng-Hong; Wensky, Allen K; Wonnacott, Keith

2010-01-01

The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical trials utilizing xenogeneic porcine pancreatic islets to treat T1D. © 2010 John Wiley & Sons A/S.

A combined park management framework based on regulatory and behavioral strategies: use of visitors' knowledge to assess effectiveness.

PubMed

Papageorgiou, K

2001-07-01

In light of the increasing mandate for greater efficiency in conservation of natural reserves such as national parks, the present study suggests educational approaches as a tool to achieve conservation purposes. Currently, the management of human-wildlife interactions is dominated by regulatory strategies, but considerable potential exists for environmental education to enhance knowledge in the short run and to prompt attitude change in the long run. A framework for conservation based on both traditional regulatory- and behavior-oriented strategies was proposed whereby the level of knowledge that park visitors have acquired comprises an obvious outcome and establishes a basis upon which the effectiveness of regulatory- and behavior-based regimes could be assessed. The perceptions regarding park-related issues of two distinct visitor groups (locals and nonlocals) are summarized from a survey undertaken in Vikos-Aoos national park. The findings suggest a superficial knowledge for certain concepts but little profound understanding of the content of such concepts, indicating that knowledge-raising efforts should go a long way towards establishing a positive attitude for the resource. Visitors' poor knowledge of the park's operation regulation contest the efficiency of the presently dominant regulatory management regime. While geographical distances did not appear to significantly differentiate knowledge between the two groups, wilderness experience (as certified by visits to other parks) was proved to be an impetus for generating substantial learner interest in critical park issues among nonlocal visitors. School education and media were found to be significant knowledge providers.

A Regulatory Framework for Nanotechnology

DTIC Science & Technology

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

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

PubMed

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

2018-01-01

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

Timing is everything :

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

Kobos, Peter Holmes; Walker, La Tonya Nicole; Malczynski, Leonard A.

People save for retirement throughout their career because it is virtually impossible to save all youll need in retirement the year before you retire. Similarly, without installing incremental amounts of clean fossil, renewable or transformative energy technologies throughout the coming decades, a radical and immediate change will be near impossible the year before a policy goal is set to be in place. Therefore, our research question is, To meet our desired technical and policy goals, what are the factors that affect the rate we must install technology to achieve these goals in the coming decades? Existing models do not includemore » full regulatory constraints due to their often complex, and inflexible approaches to solve for optimal engineering instead of robust and multidisciplinary solutions. This project outlines the theory and then develops an applied software tool to model the laboratory-to-market transition using the traditional technology readiness level (TRL) framework, but develops subsequent and a novel regulatory readiness level (RRL) and market readiness level (MRL). This tool uses the ideally-suited system dynamics framework to incorporate feedbacks and time delays. Future energy-economic-environment models, regardless of their programming platform, may adapt this software model component framework or module to further vet the likelihood of new or innovative technology moving through the laboratory, regulatory and market space. The prototype analytical framework and tool, called the Technology, Regulatory and Market Readiness Level simulation model (TRMsim) illustrates the interaction between technology research, application, policy and market dynamics as they relate to a new or innovative technology moving from the theoretical stage to full market deployment. The initial results that illustrate the models capabilities indicate for a hypothetical technology, that increasing the key driver behind each of the TRL, RRL and MRL components individually decreases the time required for the technology to progress through each component by 63, 68 and 64%, respectively. Therefore, under the current working assumptions, to decrease the time it may take for a technology to move from the conceptual stage to full scale market adoption one might consider expending additional effort to secure regulatory approval and reducing the uncertainty of the technologys demand in the marketplace.« less

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

PubMed

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

2016-03-01

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

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

NASA Astrophysics Data System (ADS)

Dhanju, Amardeep

Offshore wind power is an energy resource whose potential in the US has been recognized only recently. There is now growing interest among the coastal states to harness the resource, particularly in states adjacent to the Mid-Atlantic Bight where the shallow continental shelf allows installation of wind turbines using the existing foundation technology. But the promise of bountiful clean energy from offshore wind could be delayed or forestalled due to policy and regulatory challenges. This dissertation is an effort to identify and address some of the important challenges. Focusing on Delaware as a case study it calculates the extent of the wind resource; considers one means to facilitate resource development---the establishment of statewide and regional public power authorities; analyzes possible regulatory frameworks to manage the resource in state-controlled waters; and assesses the use of distributed storage to manage intermittent output from wind turbines. In order to cover a diversity of topics, this research uses a multi-paper format with four essays forming the body of work. The first essay lays out an accessible methodology to calculate offshore wind resource potential using publicly available data, and uses this methodology to access wind resources off Delaware. The assessment suggests a wind resource approximately four times the average electrical load in Delaware. The second essay examines the potential role of a power authority, a quasi-public institution, in lowering the cost of capital, reducing financial risk of developing and operating a wind farm, and enhancing regional collaboration on resource development and management issues. The analysis suggests that a power authority can lower the cost of offshore wind power by as much as 1/3, thereby preserving the ability to pursue cost-competitive development even if the current federal incentives are removed. The third essay addresses the existing regulatory void in state-controlled waters of Delaware. It outlines a regulatory framework touching on key elements such as the leasing system, length of tenure, and financial terms for allocating property rights. In addition, the framework also provides recommendations on environmental assessment that would be required prior to lease issuance. The fourth essay analyzes offshore wind power integration using electric thermal storage in housing units. It presents a model of wind generation, heating load and wind driven thermal storage to assess the potential of storage to buffer wind intermittency. The analysis suggests that thermal load matches the seasonal excess of offshore wind during winter months, and that electric thermal storage could provide significant temporal, spatial, and cost advantages for balancing output from offshore wind generation, while also converting a major residential load (space heating) now met by fossil fuels to low carbon energy resources. Together, the four essays provide new analyses of policy, regulatory, and system integration issues that could impede resource development, and also analyze and recommend strategies to manage these issues.

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

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

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

1997-02-01

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

Perspective for the development of companion diagnostics and regulatory landscape to encourage personalized medicine in Japan.

PubMed

Tazawa, Yoshiaki

2016-01-01

On July 1st, 2013, the Ministry of Health, Labor and Welfare (MHLW) issued an official notification regarding the co-development of companion diagnostics (CDx) with a drug which requires any exclusive diagnostic test or medical device to predict efficacy or adverse reactions to the drug. The main frame and contents in the MHLW's notification are quite similar to the summaries in the final guidance issued by the US Food and Drug Administration (FDA) on August 6th, 2014 Guidance for Industry and Food and Drug Administration Staff (In Vitro Companion Diagnostic Devices, [2014] ), and these recommend industries to develop, study and submit CDx and the corresponding drug contemporaneously as much as possible. Following the MHLW's notification, the Pharmaceutical and Medical Device Agency (PMDA) notified on December 26th, 2013, "the technical guidance for co-development of CDx and the drug" that mentioned the regulatory requirements for clinical trial of the drug and CDx as well as analytical validity of CDx required for the trials. These official notifications from the Ministry and the Agency may be useful for pharmaceutical and diagnostics makers to understand how they should co-develop and validate CDx for clinical trials and regulatory submission. However, since the most anticipated technologies such as the next generation sequencer (NGS) are more complex and its medical risks could be high level, the existing regulatory system focusing on only diagnostics reagents and devices that are developed and manufactured by in vitro diagnostics (IVD) makers may be no longer suitable for the characteristics of CDx for the future.As an increase of clinical needs for multiple biomarkers assay by DNA sequencer, on November 19th, 2013, the FDA cleared 510 K for NGS and its universal kit. On October 3rd, 2014, moreover, the agency notified two drafts of guidance (Anticipated Details of the Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratory in Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), [2014]; Anticipated Details of the Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratory in FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDT), [2014]) for oversight of laboratory developed tests (LDTs) with medium or high medical risks. These FDA's strategic decisions and new regulatory frameworks may allow the clinical laboratories to develop and perform more easily NGS-based CDx under the certification of Clinical Laboratory Improvement Amendments (CLIA). However, neither law nor regulated quality management system similar to the CLIA exists in Japan. To effectively validate LDTs and NGS for medical practice, Japan should learn more the current regulatory changes and initiatives in the US, as well as to reform the regulatory frameworks and create any regulated quality management system for clinical laboratory testing to be reimbursed.

Ethical and legal framework and regulation for off-label use: European perspective.

PubMed

Lenk, Christian; Duttge, Gunnar

2014-01-01

For more than 20 years the off-label use of drugs has been an essential part of the ethical and legal considerations regarding the international regulation of drug licensing. Despite a number of regulatory initiatives in the European Union, there seems to remain a largely unsatisfactory situation following a number of critical descriptions and statements from actors in the field. The present article gives an overview of the ethical and legal framework and developments in European countries and identifies existing problems and possible pathways for solutions in this important regulatory area. In addition to the presentation of the ethical and legal foundations, some attention is given to criticisms from medical practitioners to the current handling of off-label drug use. The review also focuses on the situation confronted by patients and physicians when off-label prescriptions are necessary. Through legal descriptions from a number of countries, possible solutions for future discussion of European health care policy are selected and explained.

Ethics, law, and commercial surrogacy: a call for uniformity.

PubMed

Drabiak, Katherine; Wegner, Carole; Fredland, Valita; Helft, Paul R

2007-01-01

In the United States at this time, no uniform federal law exists regarding commercial surrogacy, and state statutory schemes vary vastly, ranging from criminalization to legal recognition with contract enforcement. The authors examine how commercial surrogacy agencies utilize the Internet as a means for attracting parents and surrogates by employing emotional cultural rhetoric. By inducing both parents and surrogates to their jurisdiction, agencies circumvent vast discrepancies in state statutory regulative schemes and create a distinct interstate business, absent an efficient regulatory framework or legal recourse in some circumstances. The authors propose a uniform federal regulatory scheme premised upon regulating interstate business transactions to create accountability and legal remedies for both the parents and the surrogate.

Better by design: business preferences for environmental regulatory reform.

PubMed

Taylor, Christopher M; Pollard, Simon J T; Rocks, Sophie A; Angus, Andrew J

2015-04-15

We present the preferences for environmental regulatory reform expressed by 30 UK businesses and industry bodies from 5 sectors. While five strongly preferred voluntary regulation, seven expressed doubts about its effectiveness, and 18 expressed no general preference between instrument types. Voluntary approaches were valued for flexibility and lower burdens, but direct regulation offered stability and a level playing field. Respondents sought regulatory frameworks that: are coherent; balance clarity, prescription and flexibility; are enabled by positive regulatory relationships; administratively efficient; targeted according to risk magnitude and character; evidence-based and that deliver long-term market stability for regulatees. Anticipated differences in performance between types of instrument can be undermined by poor implementation. Results underline the need for policy makers and regulators to tailor an effective mix of instruments for a given sector, and to overcome analytical, institutional and political barriers to greater coherence, to better coordinate existing instruments and tackle new environmental challenges as they emerge. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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

Sangmyeon Ahn; Jungjoon Lee; Chanwoo Jeong

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

DEEP: a general computational framework for predicting enhancers

PubMed Central

Kleftogiannis, Dimitrios; Kalnis, Panos; Bajic, Vladimir B.

2015-01-01

Transcription regulation in multicellular eukaryotes is orchestrated by a number of DNA functional elements located at gene regulatory regions. Some regulatory regions (e.g. enhancers) are located far away from the gene they affect. Identification of distal regulatory elements is a challenge for the bioinformatics research. Although existing methodologies increased the number of computationally predicted enhancers, performance inconsistency of computational models across different cell-lines, class imbalance within the learning sets and ad hoc rules for selecting enhancer candidates for supervised learning, are some key questions that require further examination. In this study we developed DEEP, a novel ensemble prediction framework. DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. In our method we train many individual classification models that we combine to classify DNA regions as enhancers or non-enhancers. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues. We further present results derived using in vivo-derived enhancer data from VISTA database. DEEP-VISTA, when tested on an independent test set, achieved GM of 80.1% and accuracy of 89.64%. DEEP framework is publicly available at http://cbrc.kaust.edu.sa/deep/. PMID:25378307

Public financing of IVF: a review of policy rationales.

PubMed

Mladovsky, Philipa; Sorenson, Corinna

2010-06-01

There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed.

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

USGS Publications Warehouse

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

2017-01-01

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

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

PubMed

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

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

Regulating genetically modified food. Policy trajectories, political culture, and risk perceptions in the U.S., Canada, and EU.

PubMed

Wohlers, Anton E

2010-09-01

This paper examines whether national differences in political culture add an explanatory dimension to the formulation of policy in the area of biotechnology, especially with respect to genetically modified food. The analysis links the formulation of protective regulatory policies governing genetically modified food to both country and region-specific differences in uncertainty tolerance levels and risk perceptions in the United States, Canada, and European Union. Based on polling data and document analysis, the findings illustrate that these differences matter. Following a mostly opportunistic risk perception within an environment of high tolerance for uncertainty, policymakers in the United States and Canada modified existing regulatory frameworks that govern genetically modified food in their respective countries. In contrast, the mostly cautious perception of new food technologies and low tolerance for uncertainty among European Union member states has contributed to the creation of elaborate and stringent regulatory policies governing genetically modified food.

78 FR 70354 - Conceptual Example of a Proposed Risk Management Regulatory Framework Policy Statement

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0254] Conceptual Example of a Proposed Risk Management... issuing a document entitled: ``White Paper on a Conceptual Example of a Proposed Risk Management... ``openness,'' a white paper on a Conceptual Example of a Proposed Risk Management Regulatory Framework (RMRF...

The Australian quarantine and biosecurity legislation: Constitutionality and critique.

PubMed

Gray, Anthony

2015-06-01

Australia's quarantine and biosecurity laws have been in focus recently with the serious outbreak of the ebola virus and the not-so-serious incident involving an actor's dogs apparently gaining unauthorised access to Australia. These incidents have coincided with the move to replace Australia's existing quarantine legislation with a modern regulatory framework for managing biosecurity risks. This article critiques the existing and new Australian legislation, comparing them with approaches in other jurisdictions and discussing some relevant public policy issues. In particular, the article comments on the constitutionality of the provisions relating to the detention of individuals for public health reasons, such as to control or limit the spread of disease, finding the new legislation to be an improvement on the existing one.

'Do no harm'? Professional regulation of disabled nursing students and nurses in Great Britain.

PubMed

Sin, Chih Hoong; Fong, Janice

2008-06-01

This paper is a report of the findings of a General Formal Investigation launched by the Disability Rights Commission, Great Britain into the impact of regulatory fitness standards on disabled people, and on nursing students and nurses in particular. The potential for systemic discrimination against disabled nursing professionals lies in the existence and nature of regulatory fitness standards, as well as in how these are interpreted and implemented in practice. A review of relevant legislation, regulation and guidance was conducted to explore the interaction of the regulatory framework with the Disability Discrimination Act. A formal call to key national stakeholder organizations solicited information on perceptions of the regulatory framework and the adequacy of guidance issued. Independent research was commissioned on disabled people's disclosure of disability, informal and formal decision-making around fitness within the educational, and employment contexts. An Inquiry Panel examined all evidence sources, solicited further oral evidence from key organizations, and developed recommendations. No mention was found of the Disability Discrimination Act in any regulation and guidance governing nursing prior to 2006. There are particular requirements for 'good health and good character'. Respondents from key national stakeholder organizations, higher educational institutions and employers struggle to interpret the fitness requirements consistently. Implementation is variable, with reliance on ad hoc self-initiated strategies. The variability of interpretation and implementation can lead to discrimination against disabled people. The imprecision of fitness requirements and variability of implementation raise serious doubts about their utility in managing risk.

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

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

Lee, Jungjoon; Ahn, Sangmyeon; Choi, Kyungwoo

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

Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

PubMed

White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

2011-11-01

To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal Editors (ICMJE) and/or the World Association of Medical Editors (WAME).

An Analysis of Public Health Policy and Legal Issues Relevant to Mobile Food Vending

PubMed Central

Stevens, Stephanie A.; Yen, Irene H.; Laraia, Barbara L.

2010-01-01

Mobile food vending is a component of the food environment that has received little attention in the public health literature beyond concerns about food sanitation and hygiene issues. However, several features of mobile food vending make it an intriguing venue for food access. We present key components of mobile vending regulation and provide examples from 12 US cities to illustrate the variation that can exist surrounding these regulations. Using these regulatory features as a framework, we highlight existing examples of “healthy vending policies” to describe how mobile food vending can be used to increase access to nutritious food for vulnerable populations. PMID:20864711

Abalone farm discharges the withering syndrome pathogen into the wild

PubMed Central

Lafferty, Kevin D.; Ben-Horin, Tal

2013-01-01

An intracellular bacterium Candidatus Xenohaliotis californiensis, also called Withering-Syndrome Rickettsia-Like Organism (WS-RLO), is the cause of mass mortalities that are the chief reason for endangerment of black abalone (Haliotis cracherodii). Using a real-time PCR assay, we found that a shore-based abalone farm (AF) in Santa Barbara, CA, USA discharged WS-RLO DNA into the ocean. Several other shore-based AFs discharge effluent into critical habitat for black abalone in California and this might affect the recovery of wild black abalone. Existing regulatory frameworks exist that could help protect wild species from pathogens released from shore-based aquaculture. PMID:24367359

Abalone farm discharges the withering syndrome pathogen into the wild.

PubMed

Lafferty, Kevin D; Ben-Horin, Tal

2013-01-01

An intracellular bacterium Candidatus Xenohaliotis californiensis, also called Withering-Syndrome Rickettsia-Like Organism (WS-RLO), is the cause of mass mortalities that are the chief reason for endangerment of black abalone (Haliotis cracherodii). Using a real-time PCR assay, we found that a shore-based abalone farm (AF) in Santa Barbara, CA, USA discharged WS-RLO DNA into the ocean. Several other shore-based AFs discharge effluent into critical habitat for black abalone in California and this might affect the recovery of wild black abalone. Existing regulatory frameworks exist that could help protect wild species from pathogens released from shore-based aquaculture.

Abalone farm discharges the withering syndrome pathogen into the wild

USGS Publications Warehouse

Lafferty, Kevin D.; Ben-Horin, Tal

2014-01-01

An intracellular bacterium Candidatus Xenohaliotis californiensis, also called Withering-Syndrome Rickettsia-Like Organism (WS-RLO), is the cause of mass mortalities that are the chief reason for endangerment of black abalone (Haliotis cracherodii). Using a real-time PCR assay, we found that a shore-based abalone farm (AF) in Santa Barbara, CA, USA discharged WS-RLO DNA into the ocean. Several other shore-based AFs discharge effluent into critical habitat for black abalone in California and this might affect the recovery of wild black abalone. Existing regulatory frameworks exist that could help protect wild species from pathogens released from shore-based aquaculture.

Identification of miRNA-mRNA regulatory modules by exploring collective group relationships.

PubMed

Masud Karim, S M; Liu, Lin; Le, Thuc Duy; Li, Jiuyong

2016-01-11

microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants and animals. They regulate a wide range of biological processes by targeting messenger RNAs (mRNAs). Evidence suggests that miRNAs and mRNAs interact collectively in gene regulatory networks. The collective relationships between groups of miRNAs and groups of mRNAs may be more readily interpreted than those between individual miRNAs and mRNAs, and thus are useful for gaining insight into gene regulation and cell functions. Several computational approaches have been developed to discover miRNA-mRNA regulatory modules (MMRMs) with a common aim to elucidate miRNA-mRNA regulatory relationships. However, most existing methods do not consider the collective relationships between a group of miRNAs and the group of targeted mRNAs in the process of discovering MMRMs. Our aim is to develop a framework to discover MMRMs and reveal miRNA-mRNA regulatory relationships from the heterogeneous expression data based on the collective relationships. We propose DIscovering COllective group RElationships (DICORE), an effective computational framework for revealing miRNA-mRNA regulatory relationships. We utilize the notation of collective group relationships to build the computational framework. The method computes the collaboration scores of the miRNAs and mRNAs on the basis of their interactions with mRNAs and miRNAs, respectively. Then it determines the groups of miRNAs and groups of mRNAs separately based on their respective collaboration scores. Next, it calculates the strength of the collective relationship between each pair of miRNA group and mRNA group using canonical correlation analysis, and the group pairs with significant canonical correlations are considered as the MMRMs. We applied this method to three gene expression datasets, and validated the computational discoveries. Analysis of the results demonstrates that a large portion of the regulatory relationships discovered by DICORE is consistent with the experimentally confirmed databases. Furthermore, it is observed that the top mRNAs that are regulated by the miRNAs in the identified MMRMs are highly relevant to the biological conditions of the given datasets. It is also shown that the MMRMs identified by DICORE are more biologically significant and functionally enriched.

Investor Outlook: Solving Gene Therapy Pricing…with a Cures Voucher?

PubMed

Schimmer, Joshua; Breazzano, Steven

2016-12-01

Gene therapy reimbursement continues to be an intense topic of discussion in the field given the unique and durable benefits from a single administration and generally small patient populations against a reimbursement framework that is not optimized for such "cures" or long-lived benefits. As more gene therapy programs enter the market and late-stage development, it is increasingly important for the field to define a reimbursement model that works for all stakeholders in order to encourage the next wave of innovation. To add to the discussion around new payment models and potential solutions, we propose a flexible voucher system that takes advantage of existing infrastructure, precedent, and regulatory frameworks.

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

PubMed

Bowman, Diana M; Gatof, Jake

2015-01-01

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

Effect of land-applied biosolids on surface-water nutrient yields and groundwater quality in Orange County, North Carolina

USGS Publications Warehouse

Wagner, Chad R.; Fitzgerald, Sharon A.; McSwain, Kristen Bukowski; Harden, Stephen L.; Gurley, Laura N.; Rogers, Shane W.

2015-01-01

The data, analysis, and conclusions associated with this study can be used by regulatory agencies, resource managers, and wastewater-treatment operators to (1) better understand the quantity and characteristics of nutrients, bacteria, metals, and contaminants of emerging concern that are transported away from biosolids land-application fields to surface water and groundwater under current regulations for the purposes of establishing effective total maximum daily loads (TMDLs) and restoring impaired water resources, (2) assess how well existing regulations protect waters of the State and potentially recommend effective changes to regulations or land-application procedures, and (3) establish a framework for developing guidance on effective techniques for monitoring and regulatory enforcement of permitted biosolids land-application fields.

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

PubMed

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

2016-05-01

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

Enhancing faecal sludge management in peri-urban areas of Lusaka through faecal sludge valorisation: challenges and opportunities

NASA Astrophysics Data System (ADS)

Tembo, J. M.; Nyirenda, E.; Nyambe, I.

2017-03-01

Lusaka, the capital city of Zambia, has two million inhabitants with 70% residing in peri-urban areas. Ninety (90) % of this population employ pit latrines for excretion generating approximately 22,680 tons of faecal sludge per annum. This sludge is inadequately managed hence of the generated amount, over 60% remains within the residential environment thereby compromising both the environment and public health. To foster a solution to this problem, a study was commissioned to assess faecal sludge valorisation potential and how it would impact on Faecal Sludge Management. The study evaluated policy, institutional and regulatory frameworks, sanitation practices including latrine construction and usage aspects and also characterised the faecal sludge for selected parameters relevant to valorisation. Four peri-urban areas were adopted as study sites. Policy issues together with existing institutional and regulatory frameworks were assessed through literature review. Sanitation practices were evaluated through physical observations, focus group discussions, interviews and questionnaire administration. Faecal sludge characterisation was through sampling and analysis. It was observed that there are policy gaps in fostering faecal sludge valorisation. Sanitation practices and latrines construction also do not favour valorisation. The quality of the raw sludge has potential for valorisation though again, some parameters like solid waste content require drastic changes in sanitation practices in order not to compromise the reuse potential of the sludge. It was concluded that if faecal sludge management is to be enhanced through valorisation, there is need to have policies promoting pit latrine faecal sludge reuse and strengthened regulatory and institutional frameworks in this respect.

Gamete and Embryo Donation and Surrogacy in Australia: The Social Context and Regulatory Framework

PubMed Central

Hammarberg, Karin; Johnson, Louise; Petrillo, Tracey

2011-01-01

The social and legal acceptability of third-party reproduction varies around the world. In Australia, gamete and embryo donation and surrogacy are permitted within the regulatory framework set out by federal and state governments. The aim of this paper is to describe the social context and regulatory framework for third-party reproduction in Australia. This is a review of current laws and regulations related to third-party reproduction in Australia. Although subtle between-state differences exist, third-party reproduction is by and large a socially acceptable and legally permissible way to form a family throughout Australia. The overarching principles that govern the practice of third-party reproduction are altruism; the right of donorconceived people to be informed of their biological origins; and the provision of comprehensive counselling about the social, psychological, physical, ethical, financial and legal implications of third-party reproduction to those considering donating or receiving gametes or embryos and entering surrogacy arrangements. These principles ensure that donors are not motivated by financial gain, donor offspring can identify and meet with the person or persons who donated gametes or embryos, and prospective donors and recipients are aware of and have carefully considered the potential consequences of third-party reproduction. Australian state laws and federal guidelines prohibit commercial and anonymous third-party reproduction; mandate counselling of all parties involved in gamete and embryo donation and surrogacy arrangements; and require clinics to keep records with identifying and non- identifying information about the donor/s to allow donor-conceived offspring to trace their biological origins. PMID:24851179

Gamete and embryo donation and surrogacy in australia: the social context and regulatory framework.

PubMed

Hammarberg, Karin; Johnson, Louise; Petrillo, Tracey

2011-01-01

The social and legal acceptability of third-party reproduction varies around the world. In Australia, gamete and embryo donation and surrogacy are permitted within the regulatory framework set out by federal and state governments. The aim of this paper is to describe the social context and regulatory framework for third-party reproduction in Australia. This is a review of current laws and regulations related to third-party reproduction in Australia. Although subtle between-state differences exist, third-party reproduction is by and large a socially acceptable and legally permissible way to form a family throughout Australia. The overarching principles that govern the practice of third-party reproduction are altruism; the right of donorconceived people to be informed of their biological origins; and the provision of comprehensive counselling about the social, psychological, physical, ethical, financial and legal implications of third-party reproduction to those considering donating or receiving gametes or embryos and entering surrogacy arrangements. These principles ensure that donors are not motivated by financial gain, donor offspring can identify and meet with the person or persons who donated gametes or embryos, and prospective donors and recipients are aware of and have carefully considered the potential consequences of third-party reproduction. Australian state laws and federal guidelines prohibit commercial and anonymous third-party reproduction; mandate counselling of all parties involved in gamete and embryo donation and surrogacy arrangements; and require clinics to keep records with identifying and non- identifying information about the donor/s to allow donor-conceived offspring to trace their biological origins.

Cross-border issues in the development of medical tourism in Malaysia: legal challenges and opportunities.

PubMed

Nemie, Puteri; Kassim, Jahn

2009-08-01

Strategically located at the crossroads of Asia, Malaysia has become one of the key players in the fast-growing and lucrative market for health care services in Asia. Medical travel across international boundaries has been made possible through affordable airfares and the favourable exchange rates of the Malaysian ringgit has contributed to the rise of the "medical tourism phenomenon" where medical travel is combined with visiting popular tourist destinations in Malaysia. Further, competitive medical fees and modern medical facilities have also made Malaysia a popular destination for medical tourists. Nevertheless, the increased number of foreign patients has opened up possibilities of Malaysian health care providers being subjected to malpractice claims and triggering a myriad of cross-border legal issues. Presently, there is no internationally accepted legal framework to regulate medical tourism and issues of legal redress in relation to unsatisfactory provision of treatment across international boundaries. The economic benefits of medical tourism must be based upon a solid legal regulatory framework and strong ethical standards as well as upon high-quality medical and health care services. It is therefore important to assess the existing legal framework affecting the development of medical tourism in Malaysia in order to explore the gaps, deficiencies and possibilities for legal and regulatory reform.

Guidelines for performing systematic reviews in the development of toxicity factors.

PubMed

Schaefer, Heather R; Myers, Jessica L

2017-12-01

The Texas Commission on Environmental Quality (TCEQ) developed guidance on conducting systematic reviews during the development of chemical-specific toxicity factors. Using elements from publicly available frameworks, the TCEQ systematic review process was developed in order to supplement the existing TCEQ Guidelines for developing toxicity factors (TCEQ Regulatory Guidance 442). The TCEQ systematic review process includes six steps: 1) Problem Formulation; 2) Systematic Literature Review and Study Selection; 3) Data Extraction; 4) Study Quality and Risk of Bias Assessment; 5) Evidence Integration and Endpoint Determination; and 6) Confidence Rating. This document provides guidance on conducting a systematic literature review and integrating evidence from different data streams when developing chemical-specific reference values (ReVs) and unit risk factors (URFs). However, this process can also be modified or expanded to address other questions that would benefit from systematic review practices. The systematic review and evidence integration framework can improve regulatory decision-making processes, increase transparency, minimize bias, improve consistency between different risk assessments, and further improve confidence in toxicity factor development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

77 FR 18176 - Magnuson-Stevens Fishery Conservation and Management Act Provisions; Fisheries of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... environmental assessment (EA) was prepared for Framework 47 that describes the proposed action and other.... Copies of Framework 47, the draft EA, its Regulatory Impact Review (RIR), and the Initial Regulatory.... The Framework 47 EA/ RIR/IRFA are also accessible via the Internet at http://www.nefmc.org/nemulti...

Novel GM animal technologies and their governance.

PubMed

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

2013-08-01

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

Patient Experience Data in US Food and Drug Administration (FDA) Regulatory Decision Making:: A Policy Process Perspective.

PubMed

Kuehn, Carrie M

2018-01-01

The influence of patient advocates on FDA regulatory decision making has increased. Despite enhanced engagement with FDA, there remain challenges to achieving the regulatory goals of patients within FDA's regulatory framework. Gaps exist between patient advocates' knowledge of the agency's processes and FDA's need for rigorous, clinically meaningful patient experience data. This study examined the policy process in which patient experience data are collected by patient advocates and provided to FDA for regulatory decision making. Semistructured, narrative interviews were conducted with 14 professionals working in patient advocacy or at FDA. The purpose was to examine, in depth, participants' perceptions and experiences regarding this new regulatory process. Interviews were coded and examined for themes. The use of patient experience data by FDA is an evolving regulatory process. Participants identified a number of barriers and contributors to regulatory success. Well-organized and sophisticated patient advocacy groups with access to scientific and policy expertise are more likely to find success meeting FDA's patient experience data requirements. A conceptual model of this regulatory process was developed. Use of patient experience data by FDA has the potential to positively influence the regulation of medical products in the United States. Success within this new regulatory process will depend on clear guidance from FDA regarding the collection, analysis, and use of patient experience data. Patient advocacy groups must enhance internal capacity and expertise while engaging in substantive collaborations with FDA and other stakeholders in order to meaningfully contribute to the regulatory review of new therapeutics.

Management of Bottom Sediments Containing Toxic Substances: Proceedings of the U.S./Japan Experts Meeting (13th) Held in Baltimore, Maryland on 3-5 November 1987

DTIC Science & Technology

1992-04-01

concentration, 0.4 ppm). Within Dredging Area It is thought that the mercury concentration in fishes depends upon the mercury concentration in water, the...the original contamination are curtailed, the existence of regulatory mechanisms (and funding sources) to deal with these sources is essential. The...Water Quality Act of 1987 provides important additions to the preexisting framework of such mechanisms . REVIEW OF COASTAL SUPERFUND SITES The following

75 FR 39391 - Funding and Fiscal Affairs, Loan Policies and Operations, and Funding Operations; Capital...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

... framework. System banks do not routinely retire their stock in the ordinary course of business or revolve... adopting a Tier 1/Tier 2 regulatory capital framework for the institutions it regulates. The NCUA has also... capital requirement and, therefore, it will remain part of the System's regulatory capital framework. The...

The state of genetically modified crop regulation in Canada

PubMed Central

Smyth, Stuart J

2014-01-01

Genetically modified (GM) crops were first commercialized in Canada in 1995 and the 2014 crop represents the 20th year of successful production. Prior to the first commercialization of GM crops, Canada reviewed its existing science-based regulatory framework and adapted the existing framework to allow for risk assessments on the new technology to be undertaken in a timely and efficient manner. The result has been the rapid and widespread adoption of GM varieties of canola, corn and soybeans. The first decade of GM crop production precipitated 2 landmark legal cases relating to patent infringement and economic liability, while the second decade witnessed increased political efforts to have GM crops labeled in Canada as well as significant challenges from the low level comingling of GM crops with non-GM commodities. This article reviews the 20 y of GM crop production in Canada from a social science perspective that includes intellectual property, consumer acceptance and low level presence. PMID:25437238

Examining Privacy Regulatory Frameworks in Canada in the Context of HIV.

PubMed

Ion, Allyson

2016-05-01

In the process of receiving perinatal care, women living with HIV (WLWH) in Canada have experienced disclosure of their HIV status without their express consent. This disclosure often occurs by well-intentioned healthcare providers; however, from the perspective of WLWH, it is a breach of confidentiality and leaves WLWH to manage the consequences. This paper is a critical review of the regulatory and legislative infrastructure that exists to protect the personal health information of WLWH in Ontario and Canada; the recourse that WLWH have in the event that their confidentiality is breached; and potential approaches that could be applied to organize the system differently to decrease the chance of a privacy breach and to facilitate appropriate collection, use and disclosure of personal health information. Copyright © 2016 Longwoods Publishing.

Deep Borehole Disposal Safety Analysis.

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

Freeze, Geoffrey A.; Stein, Emily; Price, Laura L.

This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept.more » It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.« less

Assessing the health impact of transnational corporations: a case study on McDonald's Australia.

PubMed

Anaf, Julia; Baum, Frances E; Fisher, Matt; Harris, Elizabeth; Friel, Sharon

2017-02-06

The practices of transnational corporations affect population health through production methods, shaping social determinants of health, or influencing the regulatory structures governing their activities. There has been limited research on community exposures to TNC policies and practices. Our pilot research used McDonald's Australia to test methods for assessing the health impacts of one TNC within Australia. We adapted existing Health Impact Assessment methods to assess McDonald's activities. Data identifying potential impacts were sourced through document analysis, including McDonald's corporate literature; media analysis and semi-structured interviews. We commissioned a spatial and socioeconomic analysis of McDonald's restaurants in Australia through Geographic Information System technology. The data was mapped against a corporate health impact assessment framework which included McDonald's Australia's political and business practices; products and marketing; workforce, social, environmental and economic conditions; and consumers' health related behaviours. We identified both positive and detrimental aspects of McDonald's Australian operations across the scope of the CHIA framework. We found that McDonald's outlets were slightly more likely to be located in areas of lower socioeconomic status. McDonald's workplace conditions were found to be more favourable than those in many other countries which reflects compliance with Australian employment regulations. The breadth of findings revealed the need for governments to strengthen regulatory mechanisms that are conducive to health; the opportunity for McDonald's to augment their corporate social responsibility initiatives and bolster reputational endorsement; and civil society actors to inform their advocacy towards health and equity outcomes from TNC operations. Our study indicates that undertaking a corporate health impact assessment is possible, with the different methods revealing sufficient information to realise that strong regulatory frameworks are need to help to avoid or to mediate negative health impacts.

The oil rich Niger Delta region: a framework for improved performance of the Nigerian regulatory process.

PubMed

Onu, N Chukemeka Hemanachi

2003-06-01

The adoption of this policy framework has the ability to reconcile industry, the environment and community interests, taking into account all factors that are relevant to managing developments that are both sustainable and contributory to the achievement of industrial and community stability. The management of resource development is crucial in sustaining the Niger Delta ecosystem and the human population resident in the Niger Delta region. If these separate bodies are constituted they would have the potential to reduce and discourage: i) the vulnerability of the regulatory body to influential and powerful multinational oil companies; ii) the proclivity for unaccountability to the people of the Niger Delta region, since the people of the Niger Delta would have access to the regulatory body's classified and unclassified information, and are part of the decision-making process; and iii) a reduction in conflict between the oil mining companies and the aggrieved youths of the oil rich Niger Delta region. This policy framework also has the added advantage of producing high quality decisions and more acceptable decisions than those for which the people of the Niger Delta region are excluded from the processes that concern their existence. The agency decision-making could now become a multilateral process and thus promote and enhance the accurate, impartial and rational application of legislative directives to given cases or classes of cases. Most importantly, the Minister of Petroleum Resources should be empowered by legislation to revoke any license or lease in respect of an area designated as marginal if left undeveloped for a period of 5 years and grant a lease or license for the area to a more responsible oil company.

Inferring data-specific micro-RNA function through the joint ranking of micro-RNA and pathways from matched micro-RNA and gene expression data.

PubMed

Patrick, Ellis; Buckley, Michael; Müller, Samuel; Lin, David M; Yang, Jean Y H

2015-09-01

In practice, identifying and interpreting the functional impacts of the regulatory relationships between micro-RNA and messenger-RNA is non-trivial. The sheer scale of possible micro-RNA and messenger-RNA interactions can make the interpretation of results difficult. We propose a supervised framework, pMim, built upon concepts of significance combination, for jointly ranking regulatory micro-RNA and their potential functional impacts with respect to a condition of interest. Here, pMim directly tests if a micro-RNA is differentially expressed and if its predicted targets, which lie in a common biological pathway, have changed in the opposite direction. We leverage the information within existing micro-RNA target and pathway databases to stabilize the estimation and annotation of micro-RNA regulation making our approach suitable for datasets with small sample sizes. In addition to outputting meaningful and interpretable results, we demonstrate in a variety of datasets that the micro-RNA identified by pMim, in comparison to simpler existing approaches, are also more concordant with what is described in the literature. This framework is implemented as an R function, pMim, in the package sydSeq available from http://www.ellispatrick.com/r-packages. jean.yang@sydney.edu.au Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Advancing the Adverse Outcome Pathway Framework - an ...

EPA Pesticide Factsheets

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

Organizing Environmental Flow Frameworks to Meet Hydropower Mitigation Needs

NASA Astrophysics Data System (ADS)

McManamay, Ryan A.; Brewer, Shannon K.; Jager, Henriette I.; Troia, Matthew J.

2016-09-01

The global recognition of the importance of natural flow regimes to sustain the ecological integrity of river systems has led to increased societal pressure on the hydropower industry to change plant operations to improve downstream aquatic ecosystems. However, a complete reinstatement of natural flow regimes is often unrealistic when balancing water needs for ecosystems, energy production, and other human uses. Thus, stakeholders must identify a prioritized subset of flow prescriptions that meet ecological objectives in light of realistic constraints. Yet, isolating aspects of flow regimes to restore downstream of hydropower facilities is among the greatest challenges of environmental flow science due, in part, to the sheer volume of available environmental flow tools in conjunction with complex negotiation-based regulatory procedures. Herein, we propose an organizational framework that structures information and existing flow paradigms into a staged process that assists stakeholders in implementing environmental flows for hydropower facilities. The framework identifies areas where regulations fall short of the needed scientific process, and provide suggestions for stakeholders to ameliorate those situations through advanced preparation. We highlight the strengths of existing flow paradigms in their application to hydropower settings and suggest when and where tools are most applicable. Our suggested framework increases the effectiveness and efficiency of the e-flow implementation process by rapidly establishing a knowledge base and decreasing uncertainty so more time can be devoted to filling knowledge gaps. Lastly, the framework provides the structure for a coordinated research agenda to further the science of environmental flows related to hydropower environments.

Organizing environmental flow frameworks to meet hydropower mitigation needs

USGS Publications Warehouse

McManamay, Ryan A.; Brewer, Shannon K.; Jager, Henriette; Troia, Matthew J.

2016-01-01

The global recognition of the importance of natural flow regimes to sustain the ecological integrity of river systems has led to increased societal pressure on the hydropower industry to change plant operations to improve downstream aquatic ecosystems. However, a complete reinstatement of natural flow regimes is often unrealistic when balancing water needs for ecosystems, energy production, and other human uses. Thus, stakeholders must identify a prioritized subset of flow prescriptions that meet ecological objectives in light of realistic constraints. Yet, isolating aspects of flow regimes to restore downstream of hydropower facilities is among the greatest challenges of environmental flow science due, in part, to the sheer volume of available environmental flow tools in conjunction with complex negotiation-based regulatory procedures. Herein, we propose an organizational framework that structures information and existing flow paradigms into a staged process that assists stakeholders in implementing environmental flows for hydropower facilities. The framework identifies areas where regulations fall short of the needed scientific process, and provide suggestions for stakeholders to ameliorate those situations through advanced preparation. We highlight the strengths of existing flow paradigms in their application to hydropower settings and suggest when and where tools are most applicable. Our suggested framework increases the effectiveness and efficiency of the e-flow implementation process by rapidly establishing a knowledge base and decreasing uncertainty so more time can be devoted to filling knowledge gaps. Lastly, the framework provides the structure for a coordinated research agenda to further the science of environmental flows related to hydropower environments.

Organizing Environmental Flow Frameworks to Meet Hydropower Mitigation Needs.

PubMed

McManamay, Ryan A; Brewer, Shannon K; Jager, Henriette I; Troia, Matthew J

2016-09-01

The global recognition of the importance of natural flow regimes to sustain the ecological integrity of river systems has led to increased societal pressure on the hydropower industry to change plant operations to improve downstream aquatic ecosystems. However, a complete reinstatement of natural flow regimes is often unrealistic when balancing water needs for ecosystems, energy production, and other human uses. Thus, stakeholders must identify a prioritized subset of flow prescriptions that meet ecological objectives in light of realistic constraints. Yet, isolating aspects of flow regimes to restore downstream of hydropower facilities is among the greatest challenges of environmental flow science due, in part, to the sheer volume of available environmental flow tools in conjunction with complex negotiation-based regulatory procedures. Herein, we propose an organizational framework that structures information and existing flow paradigms into a staged process that assists stakeholders in implementing environmental flows for hydropower facilities. The framework identifies areas where regulations fall short of the needed scientific process, and provide suggestions for stakeholders to ameliorate those situations through advanced preparation. We highlight the strengths of existing flow paradigms in their application to hydropower settings and suggest when and where tools are most applicable. Our suggested framework increases the effectiveness and efficiency of the e-flow implementation process by rapidly establishing a knowledge base and decreasing uncertainty so more time can be devoted to filling knowledge gaps. Lastly, the framework provides the structure for a coordinated research agenda to further the science of environmental flows related to hydropower environments.

Global regulatory framework for production and marketing of crops biofortified with vitamins and minerals.

PubMed

Mejia, Luis A; Dary, Omar; Boukerdenna, Hala

2017-02-01

Biofortification of crops is being introduced in several countries as a strategy to reduce micronutrient deficiencies. Biofortified products, with increased contents of micronutrients, are currently produced by conventional plant breeding, genetic modification, or nutrient-enhanced fertilization. Corn, rice, wheat, beans, pearl millet, sweet potato, and cassava have been biofortified with increased contents of provitamin A carotenoids, iron, or zinc. However, regulatory considerations are rare or nonexistent. The objective of this paper is to review the regulatory framework for production and marketing of biofortified crops in countries that have adopted this strategy. The information was identified using Internet search engines and websites of health and nutrition organizations and nongovernmental organizations and by consulting scientists and government authorities. Thus far, biofortified products introduced in Latin America, Africa, and Asia have been produced only by conventional breeding. Cultivars using other techniques are still under testing. The production and marketing of these products have been conducted without regulatory framework and under limited government control or regulatory guidance. Nevertheless, some countries have integrated biofortified crops into their nutrition agendas. Although improvements by conventional breeding have not been subject to regulations, when biofortification becomes expanded by including other techniques, an appropriate regulatory framework will be necessary. © 2016 New York Academy of Sciences.

Determining causal miRNAs and their signaling cascade in diseases using an influence diffusion model.

PubMed

Nalluri, Joseph J; Rana, Pratip; Barh, Debmalya; Azevedo, Vasco; Dinh, Thang N; Vladimirov, Vladimir; Ghosh, Preetam

2017-08-15

In recent studies, miRNAs have been found to be extremely influential in many of the essential biological processes. They exhibit a self-regulatory mechanism through which they act as positive/negative regulators of expression of genes and other miRNAs. This has direct implications in the regulation of various pathophysiological conditions, signaling pathways and different types of cancers. Studying miRNA-disease associations has been an extensive area of research; however deciphering miRNA-miRNA network regulatory patterns in several diseases remains a challenge. In this study, we use information diffusion theory to quantify the influence diffusion in a miRNA-miRNA regulation network across multiple disease categories. Our proposed methodology determines the critical disease specific miRNAs which play a causal role in their signaling cascade and hence may regulate disease progression. We extensively validate our framework using existing computational tools from the literature. Furthermore, we implement our framework on a comprehensive miRNA expression data set for alcohol dependence and identify the causal miRNAs for alcohol-dependency in patients which were validated by the phase-shift in their expression scores towards the early stages of the disease. Finally, our computational framework for identifying causal miRNAs implicated in diseases is available as a free online tool for the greater scientific community.

Recommendations on chemicals management policy and legislation in the framework of the Egyptian-German twinning project on hazardous substances and waste management.

PubMed

Wagner, Burkhard O; Aziz, Elham Refaat Abdel; Schwetje, Anja; Shouk, Fatma Abou; Koch-Jugl, Juliane; Braedt, Michael; Choudhury, Keya; Weber, Roland

2013-04-01

The sustainable management of chemicals and their associated wastes-especially legacy stockpiles-is always challenging. Developing countries face particular difficulties as they often have insufficient treatment and disposal capacity, have limited resources and many lack an appropriate and effective regulatory framework. This paper describes the objectives and the approach of the Egyptian-German Twinning Project under the European Neighbourhood Policy to improve the strategy of managing hazardous substances in the Egyptian Environmental Affairs Agency (EEAA) between November 2008 and May 2011. It also provides an introduction to the Republic of Egypt's legal and administrative system regarding chemical controls. Subsequently, options for a new chemical management strategy consistent with the recommendations of the United Nations Chemicals Conventions are proposed. The Egyptian legal and administrative system is discussed in relation to the United Nations' recommendations and current European Union legislation for the sound management of chemicals. We also discuss a strategy for the EEAA to use the existing Egyptian legal system to implement the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals, the Stockholm Convention and other proposed regulatory frameworks. The analysis, the results, and the recommendations presented may be useful for other developing countries in a comparable position to Egypt aspiring to update their legislation and administration to the international standards of sound management of chemicals.

A retrospective analysis of in vivo eye irritation, skin irritation and skin sensitisation studies with agrochemical formulations: Setting the scene for development of alternative strategies.

PubMed

Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Macleod, F; Mehta, J

2017-10-01

Analysis of the prevalence of health effects in large scale databases is key in defining testing strategies within the context of Integrated Approaches on Testing and Assessment (IATA), and is relevant to drive policy changes in existing regulatory toxicology frameworks towards non-animal approaches. A retrospective analysis of existing results from in vivo skin irritation, eye irritation, and skin sensitisation studies on a database of 223 agrochemical formulations is herein published. For skin or eye effects, high prevalence of mild to non-irritant formulations (i.e. per GHS, CLP or EPA classification) would generally suggest a bottom-up approach. Severity of erythema or corneal opacity, for skinor eye effects respectively, were the key drivers for classification, consistent with existing literature. The reciprocal predictivity of skin versus eye irritation and the good negative predictivity of the GHS additivity calculation approach (>85%) provided valuable non-testing evidence for irritation endpoints. For dermal sensitisation, concordance on data from three different methods confirmed the high false negative rate for the Buehler method in this product class. These results have been reviewed together with existing literature on the use of in vitro alternatives for agrochemical formulations, to propose improvements to current regulatory strategies and to identify further research needs. Copyright © 2017 Elsevier Inc. All rights reserved.

Redesigning the regulatory framework for ambulatory care services in New York.

PubMed

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

2014-12-01

Policy Points: The landscape of ambulatory care services in the United States is rapidly changing on account of payment reform, primary care transformation, and the rise of convenient care options such as retail clinics. New York State has undertaken a redesign of regulatory policy for ambulatory care rooted in the Triple Aim (better health, higher-quality care, lower costs)-with a particular emphasis on continuity of care for patients. Key tenets of the regulatory approach include defining and tracking the taxonomy of ambulatory care services as well as ensuring that convenient care options do not erode continuity of care for patients. While hospitals remain important centers of gravity in the health system, services are increasingly being delivered through ambulatory care. This shift to ambulatory care is giving rise to new delivery structures, such as retail clinics and urgent care centers, as well as reinventing existing ambulatory care capacity, as seen with the patient-centered medical home model and the movement toward team-based care. To protect the public's interests, oversight of ambulatory care services must keep pace with these rapid changes. With this purpose, in January 2013 the New York Public Health and Health Planning Council undertook a redesign of the regulatory framework for the state's ambulatory care services. This article describes the principles undergirding the framework as well as the regulatory recommendations themselves. We explored and analyzed the regulation of ambulatory care services in New York in accordance with the available gray and peer-reviewed literature and legislative documents. The deliberations of the Public Health and Health Planning Council informed our review. The vision of high-performing ambulatory care should be rooted in the Triple Aim (better health, higher-quality care, lower costs), with a particular emphasis on continuity of care for patients. There is a pressing need to better define the taxonomy of ambulatory care services. From the state government's perspective, this clarification requires better reporting from new health care entities (eg, retail clinics), connections with regional and state health information technology hubs, and coordination among state agencies. A uniform nomenclature also would improve consumers' understanding of rights and responsibilities. Finally, the regulatory mechanisms employed-from mandatory reporting to licensure to regional planning to the certificate of need-should remain flexible and match the degree of consensus regarding the appropriate regulatory path. Few other states have embarked on a wide-ranging assessment of their regulation of ambulatory care services. By moving toward adopting the regulatory approach described here, New York aims to balance sound oversight with pluralism and innovation in health care delivery. © 2014 Milbank Memorial Fund.

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

PubMed

Reid, Natasha; Petrenko, Christie L M

2018-06-01

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

Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

PubMed

Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

2017-09-01

Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

Using science soundly: The Yucca Mountain standard

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

Fri, R.W.

1995-09-01

Using sound science to shape government regulation is one of the most hotly argued topics in the ongoing debate about regulatory reform. Even though no one advaocates using unsound science, the belief that even the best science will sweep away regulatory controversy is equally foolish. As chair of a National Research Council (NRC) committee that studied the scientific basis for regulating high-level nuclear waste disposal, the author learned that science alone could resolve few of the key regulatory questions. Developing a standard that specifies a socially acceptable limit on the human health effects of nuclear waste releases involves many decisions.more » As the NRC committee learned in evaluating the scientific basis for the Yucca Mountain standard, a scientifically best decision rarely exists. More often, science can only offer a useful framework and starting point for policy debates. And sometimes, science`s most helpful contribution is to admit that it has nothing to say. The Yucca mountain study clearly illustrates that excessive faith in the power of science is more likely to produce messy frustration than crisp decisions. A better goal for regulatory reform is the sound use of science to clarify and contain the inevitable policy controversy.« less

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

PubMed

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

2003-03-01

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

What to consider when regulating electronic cigarettes: Pros, cons and unintended consequences.

PubMed

Caponnetto, Pasquale; Saitta, Daniela; Sweanor, David; Polosa, Riccardo

2015-06-01

Many public health experts, medical research societies, large health organizations and policy makers have expressed concerns about the increased popularity of electronic cigarettes and have pushed for more restrictive measures ranging from complete bans to tight regulations of these products either as medicines or as tobacco products. But these concerns have never been adequately qualified nor quantified. Without judicious assessment and thorough evaluation, regulations may have unintended consequences that can do more damage than good in public health terms. In this article, we will appraise the existing prominent regulatory frameworks for e-cigarettes, namely, general consumer product, medicinal product and tobacco product regulation, to highlight their pros and cons. Moreover, we provide concrete examples of the unintended consequences which may arise from inappropriate regulatory action. Copyright © 2015 Elsevier B.V. All rights reserved.

Registration of Medical Devices

PubMed Central

George, Bobby

2010-01-01

Globally the medical device (MD) market has been growing quite rapidly over the past decade. The regulatory framework for pharmaceuticals and devices differ substantially. The regulatory authorities in different regions of the world recognize different classes of medical devices (MDs), based on their design complexity, their use characteristics, and their potential for harm, if misused. With the vast majority of MDs in developing countries being imported, the respective governments need to put in place policies & regulations to address all elements related to MDs, ranging from its development, manufacturing, registration to post-marketing obligations & disposal so that public can have access to high quality, safe & affordable products for appropriate use. This article highlights current regulations pertaining to registration of MDs in India, in light of those existing in Global Harmonization Task Force (GHTF) member countries & Association of Southeast Asian Nations (ASEAN) countries. PMID:21814626

Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities.

PubMed

Tan, Karin Y M; van der Beek, Eline M; Chan, M Y; Zhao, Xuejun; Stevenson, Leo

2015-09-01

The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2014-01-01

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

Legacies of Lead in Charm City’s Soil: Lessons from the Baltimore Ecosystem Study

PubMed Central

Schwarz, Kirsten; Pouyat, Richard V.; Yesilonis, Ian

2016-01-01

Understanding the spatial distribution of soil lead has been a focus of the Baltimore Ecosystem Study since its inception in 1997. Through multiple research projects that span spatial scales and use different methodologies, three overarching patterns have been identified: (1) soil lead concentrations often exceed state and federal regulatory limits; (2) the variability of soil lead concentrations is high; and (3) despite multiple sources and the highly heterogeneous and patchy nature of soil lead, discernable patterns do exist. Specifically, housing age, the distance to built structures, and the distance to a major roadway are strong predictors of soil lead concentrations. Understanding what drives the spatial distribution of soil lead can inform the transition of underutilized urban space into gardens and other desirable land uses while protecting human health. A framework for management is proposed that considers three factors: (1) the level of contamination; (2) the desired land use; and (3) the community’s preference in implementing the desired land use. The goal of the framework is to promote dialogue and resultant policy changes that support consistent and clear regulatory guidelines for soil lead, without which urban communities will continue to be subject to the potential for lead exposure. PMID:26861371

Linked health data for pharmacovigilance in children: perceived legal and ethical issues for stakeholders and data guardians.

PubMed

Hopf, Yvonne Marina; Bond, Christine B; Francis, Jill J; Haughney, John; Helms, Peter J

2014-02-12

The inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data. Qualitative study using semistructured face-to-face interviews addressing the study aims. Purposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach. Participants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified. A large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.

75 FR 36211 - Requirements for Distribution of Byproduct Material

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

.... Submitting Comments and Accessing Information II. Background A. Introduction B. Regulatory Framework III.... Introduction The Commission has authority to issue both general and specific licenses for the use of byproduct... Products As noted in the introduction on regulatory framework, class exemptions allow the Commission to...

Evolutionary toxicology: Meta-analysis of evolutionary events in response to chemical stressors.

PubMed

M Oziolor, Elias; De Schamphelaere, Karel; Matson, Cole W

2016-12-01

The regulatory decision-making process regarding chemical safety is most often informed by evidence based on ecotoxicity tests that consider growth, reproduction and survival as end-points, which can be quantitatively linked to short-term population outcomes. Changes in these end-points resulting from chemical exposure can cause alterations in micro-evolutionary forces (mutation, drift, selection and gene flow) that control the genetic composition of populations. With multi-generation exposures, anthropogenic contamination can lead to a population with an altered genetic composition, which may respond differently to future stressors. These evolutionary changes are rarely discussed in regulatory or risk assessment frameworks, but the growing body of literature that documents their existence suggests that these important population-level impacts should be considered. In this meta-analysis we have compared existing contamination levels of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) that have been documented to be associated with evolutionary changes in resident aquatic organisms to regulatory benchmarks for these contaminants. The original intent of this project was to perform a meta-analysis on evolutionary events associated with PCB and PAH contamination. However, this effort was hindered by a lack of consistency in congener selection for "total" PCB or PAH measurements. We expanded this manuscript to include a discussion of methods used to determine PCB and PAH total contamination in addition to comparing regulatory guidelines and contamination that has caused evolutionary effects. Micro-evolutionary responses often lead populations onto unique and unpredictable trajectories. Therefore, to better understand the risk of population-wide alterations occurring, we need to improve comparisons of chemical contamination between affected locations. In this manuscript we offer several possibilities to unify chemical comparisons for PCBs and PAHs that would improve comparability among evolutionary toxicology investigations, and with regulatory guidelines. In addition, we identify studies documenting evolutionary change in the presence of PCB and PAH contamination levels below applicable regulatory benchmarks.

Opportunities to Apply the 3Rs in Safety Assessment Programs

PubMed Central

Sewell, Fiona; Edwards, Joanna; Prior, Helen; Robinson, Sally

2016-01-01

Abstract Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans. PMID:28053076

An Appetite for Modernizing the Regulatory Framework for Protein Content Claims in Canada.

PubMed

Marinangeli, Christopher P F; Foisy, Samara; Shoveller, Anna K; Porter, Cara; Musa-Veloso, Kathy; Sievenpiper, John L; Jenkins, David J A

2017-08-23

The need for protein-rich plant-based foods continues as dietary guidelines emphasize their contribution to healthy dietary patterns that prevent chronic disease and promote environmental sustainability. However, the Canadian Food and Drug Regulations provide a regulatory framework that can prevent Canadian consumers from identifying protein-rich plant-based foods. In Canada, protein nutrient content claims are based on the protein efficiency ratio (PER) and protein rating method, which is based on a rat growth bioassay. PERs are not additive, and the protein rating of a food is underpinned by its Reasonable Daily Intake. The restrictive nature of Canada's requirements for supporting protein claims therefore presents challenges for Canadian consumers to adapt to a rapidly changing food environment. This commentary will present two options for modernizing the regulatory framework for protein content claims in Canada. The first and preferred option advocates that protein quality not be considered in the determination of the eligibility of a food for protein content claims. The second and less preferred option, an interim solution, is a framework for adopting the protein digestibility corrected amino acid score as the official method for supporting protein content and quality claims and harmonizes Canada's regulatory framework with that of the USA.

A Framework for Integrating Environmental Justice in Regulatory Analysis

PubMed Central

Nweke, Onyemaechi C.

2011-01-01

With increased interest in integrating environmental justice into the process for developing environmental regulations in the United States, analysts and decision makers are confronted with the question of what methods and data can be used to assess disproportionate environmental health impacts. However, as a first step to identifying data and methods, it is important that analysts understand what information on equity impacts is needed for decision making. Such knowledge originates from clearly stated equity objectives and the reflection of those objectives throughout the analytical activities that characterize Regulatory Impact Analysis (RIA), a process that is traditionally used to inform decision making. The framework proposed in this paper advocates structuring analyses to explicitly provide pre-defined output on equity impacts. Specifically, the proposed framework emphasizes: (a) defining equity objectives for the proposed regulatory action at the onset of the regulatory process, (b) identifying specific and related sub-objectives for key analytical steps in the RIA process, and (c) developing explicit analytical/research questions to assure that stated sub-objectives and objectives are met. In proposing this framework, it is envisioned that information on equity impacts informs decision-making in regulatory development, and that this is achieved through a systematic and consistent approach that assures linkages between stated equity objectives, regulatory analyses, selection of policy options, and the design of compliance and enforcement activities. PMID:21776235

Ayurvedic medicine in Mauritius: Profile of Ayurvedic outlet, use, sale, distribution, regulation and importation.

PubMed

Elaheebocus, Naailah; Mahomoodally, M Fawzi

2017-02-02

Ayurvedic medicine (AM) is a legalised alternative traditional medical system in the multicultural tropical island of Mauritius. A panoply of Ayurvedic specialised shops/centres involved in the provision of Ayurvedic services hereafter termed as 'outlets' operates in different regions of the island and is extensively exploited by a significant number of Mauritians. Nonetheless, there is currently no study geared towards studying the status of AM and profile of Ayurvedic outlets in Mauritius and there is undoubtedly a dearth of standardized regulatory framework governing the practice of AM in Mauritius. The present study attempts to study the profile of Ayurvedic outlets, sale, distribution, regulation and importation of AM in Mauritius. To evaluate the characteristics profile of Ayurvedic shops/clinics/pharmacies/centres, to document common Ayurvedic products used in the treatment and management of diseases, and to analyse existing regulatory control of AM in Mauritius. Ayurvedic outlets were identified using a random approach. Once permission granted, outlets were visited where face-to-face interviews with Ayurvedic practitioners/directors/dispensers were undertaken using a semi-structured questionnaire. The characteristics of the outlets with respect to the type of business registration, procurement and dispensing of products, registration and qualification of personnels employed amongst others were studied. The International Classification of Diseases (ICD) 10 was used to classify common AM dispensed to patients. Additionally, information was sought from local authorities pertaining to existing legislation governing the importation and regulation of AM in Mauritius. A total of 16 Ayurvedic outlets ('pharmacies' (n=3), clinics (n=2), shops (n=5) and centres (n=6)) was surveyed. Six outlets dispensed AM strictly on prescription only after consultation with an onsite full-time employed registered Ayurvedic practitioner. Seven outlets offered AM both on prescription and over-the-counter where consultation was not mandatory. The remaining three outlets, where no Ayurvedic practitioner was employed, did not offer consultation at any time and dispensed the medicines over-the-counter most of the time. There is currently no such legal framework that acknowledges the existence of an Ayurvedic pharmacy in Mauritius and no trained Ayurvedic pharmacist was recruited in any of the outlets. It was also found that no specific requirements were in place to establish an Ayurvedic outlet in Mauritius. A wide variety of Ayurvedic formulated and single herb products were recorded to be in use against common diseases. Ayurvedic products were imported from India (n=10), purchased from local suppliers (n=6) or locally manufactured (n=1). The Traditional Medicine Board under the aegis of the pharmacy board is a regulatory body which requires Ayurvedic practitioners to be registered so as to practice AM in Mauritius. Additionally, the government has an Ayurvedic committee, under the aegis of the Pharmacy board in the Ministry of Health and Quality of Life to monitor the importation of AM. However, no legal framework has been enacted to regulate the sale of AM under prescription or under the supervision of an Ayurvedic practitioner. The current regulatory framework is such that the sale/use/distribution of AM is not strictly controlled unlike its importation. This has led to a certain form of unregulated practice in the private sector whereby the dispensing and sale of AM are being done over-the-counter without professional recommendations. It is recommended that authorities need to regulate the Ayurvedic medical system in Mauritius by amending stringent laws to ensure safety of patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Star on the horizon: The emergence of the direct broadcast satellite in American mass communications

NASA Astrophysics Data System (ADS)

Thomas, J. H.

1984-12-01

The purpose of this thesis is to describe the concept of broadcasting from satellites directly to the viewer equipped with a small, inexpensive receiving antenna, and the evolution of this technology as a means of commercial broadcast. Emphasis is placed on the problems of developing a regulatory framework for DBS by the Federal Communications Commission. The opposition of the existing broadcasters to the unregulated development of direct broadcast satellite (DBS) is explored in light of the possible effect that DBS may have on the economic base, audience, and advertising revenue of existing broadcasters. The information for this study was obtained from government documents, legal journals, books and the popular press. Two basic conclusions are drawn from this study: First, that the existing broadcasters have opposed the marketplace development of DBS, and second, that DBS does not pose as great a threat, at least in the near term, as the broadcasters fear.

Biobanking and Privacy Law in Brazil.

PubMed

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

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

Yu, Yang; Zeng, Zheng

2009-10-01

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

Hours of work and rest in the rail industry.

PubMed

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

2013-06-01

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

Organizing environmental flow frameworks to meet hydropower mitigation needs

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

McManamay, Ryan A.; Brewer, Shannon K.; Jager, Henriette I.

The global recognition of the importance of natural flow regimes to sustain the ecological integrity of river systems has led to increased societal pressure on the hydropower industry to change plant operations to improve downstream aquatic ecosystems. However, a complete reinstatement of natural flow regimes is often unrealistic when balancing water needs for ecosystems, energy production, and other human uses. Thus, stakeholders must identify a prioritized subset of flow prescriptions that meet ecological objectives in light of realistic constraints. Yet, isolating aspects of flow regimes to restore downstream of hydropower facilities is among the greatest challenges of environmental flow sciencemore » due, in part, to the sheer volume of available environmental flow tools in conjunction with complex negotiation-based regulatory procedures. Here, we propose an organizational framework that structures information and existing flow paradigms into a staged process that assists stakeholders in implementing environmental flows for hydropower facilities. The framework identifies areas where regulations fall short of the needed scientific process, and provide suggestions for stakeholders to ameliorate those situations through advanced preparation. We highlight the strengths of existing flow paradigms in their application to hydropower settings and suggest when and where tools are most applicable. In conclusion, our suggested framework increases the effectiveness and efficiency of the e-flow implementation process by rapidly establishing a knowledge base and decreasing uncertainty so more time can be devoted to filling knowledge gaps. As a result, the framework provides the structure for a coordinated research agenda to further the science of environmental flows related to hydropower environments.« less

A Conceptual Framework for Understanding Unintended Prolonged Opioid Use.

PubMed

Hooten, W Michael; Brummett, Chad M; Sullivan, Mark D; Goesling, Jenna; Tilburt, Jon C; Merlin, Jessica S; St Sauver, Jennifer L; Wasan, Ajay D; Clauw, Daniel J; Warner, David O

2017-12-01

An urgent need exists to better understand the transition from short-term opioid use to unintended prolonged opioid use (UPOU). The purpose of this work is to propose a conceptual framework for understanding UPOU that posits the influence of 3 principal domains that include the characteristics of (1) individual patients, (2) the practice environment, and (3) opioid prescribers. Although no standardized method exists for developing a conceptual framework, the process often involves identifying corroborative evidence, leveraging expert opinion to identify factors for inclusion in the framework, and developing a graphic depiction of the relationships between the various factors and the clinical problem of interest. Key patient characteristics potentially associated with UPOU include (1) medical and mental health conditions; (2) pain etiology; (3) individual affective, behavioral, and neurophysiologic reactions to pain and opioids; and (4) sociodemographic factors. Also, UPOU could be influenced by structural and health care policy factors: (1) the practice environment, including the roles of prescribing clinicians, adoption of relevant practice guidelines, and clinician incentives or disincentives, and (2) the regulatory environment. Finally, characteristics inherent to clinicians that could influence prescribing practices include (1) training in pain management and opioid use; (2) personal attitudes, knowledge, and beliefs regarding the risks and benefits of opioids; and (3) professionalism. As the gatekeeper to opioid access, the behavior of prescribing clinicians directly mediates UPOU, with the 3 domains interacting to determine this behavior. This proposed conceptual framework could guide future research on the topic and allow plausible hypothesis-based interventions to reduce UPOU. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Organizing environmental flow frameworks to meet hydropower mitigation needs

DOE PAGES

McManamay, Ryan A.; Brewer, Shannon K.; Jager, Henriette I.; ...

2016-06-25

The global recognition of the importance of natural flow regimes to sustain the ecological integrity of river systems has led to increased societal pressure on the hydropower industry to change plant operations to improve downstream aquatic ecosystems. However, a complete reinstatement of natural flow regimes is often unrealistic when balancing water needs for ecosystems, energy production, and other human uses. Thus, stakeholders must identify a prioritized subset of flow prescriptions that meet ecological objectives in light of realistic constraints. Yet, isolating aspects of flow regimes to restore downstream of hydropower facilities is among the greatest challenges of environmental flow sciencemore » due, in part, to the sheer volume of available environmental flow tools in conjunction with complex negotiation-based regulatory procedures. Here, we propose an organizational framework that structures information and existing flow paradigms into a staged process that assists stakeholders in implementing environmental flows for hydropower facilities. The framework identifies areas where regulations fall short of the needed scientific process, and provide suggestions for stakeholders to ameliorate those situations through advanced preparation. We highlight the strengths of existing flow paradigms in their application to hydropower settings and suggest when and where tools are most applicable. In conclusion, our suggested framework increases the effectiveness and efficiency of the e-flow implementation process by rapidly establishing a knowledge base and decreasing uncertainty so more time can be devoted to filling knowledge gaps. As a result, the framework provides the structure for a coordinated research agenda to further the science of environmental flows related to hydropower environments.« less

Gene regulatory networks reused to build novel traits: co-option of an eye-related gene regulatory network in eye-like organs and red wing patches on insect wings is suggested by optix expression.

PubMed

Monteiro, Antónia

2012-03-01

Co-option of the eye developmental gene regulatory network may have led to the appearance of novel functional traits on the wings of flies and butterflies. The first trait is a recently described wing organ in a species of extinct midge resembling the outer layers of the midge's own compound eye. The second trait is red pigment patches on Heliconius butterfly wings connected to the expression of an eye selector gene, optix. These examples, as well as others, are discussed regarding the type of empirical evidence and burden of proof that have been used to infer gene network co-option underlying the origin of novel traits. A conceptual framework describing increasing confidence in inference of network co-option is proposed. Novel research directions to facilitate inference of network co-option are also highlighted, especially in cases where the pre-existent and novel traits do not resemble each other. Copyright © 2012 WILEY Periodicals, Inc.

Examination of the regulatory frameworks applicable to biologic drugs (including stem cells and their progeny) in Europe, the U.S., and Australia: part II--a method of software documentary analysis.

PubMed

Ilic, Nina; Savic, Snezana; Siegel, Evan; Atkinson, Kerry; Tasic, Ljiljana

2012-12-01

A wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Eighteen high-tier documents from the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) regulatory frameworks were subject to automated text analysis. Selected documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Concepts, themes, and their co-occurrence were identified and compared. The most frequent concepts in TGA, FDA, and EMA frameworks were "biological," "product," and "medicinal," respectively. This was consistent with the previous manual terminology search. Good Manufacturing Practice documents, across frameworks, identified "quality" and "appropriate" as main concepts, whereas in Good Clinical Practice (GCP) documents it was "clinical," followed by "trial," "subjects," "sponsor," and "data." GCP documents displayed considerably higher concordance between different regulatory frameworks, as demonstrated by a smaller number of concepts, similar size, and similar distance between them. Although high-tier documents often use different terminology, they share concepts and themes. This paper may be a modest contribution to the recognition of similarities and differences between analyzed regulatory documents. It may also fill the literature gap and provide some foundation for future comparative research of biologic drug regulations on a global level.

Modeling gene regulatory network motifs using statecharts

PubMed Central

2012-01-01

Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

An Appetite for Modernizing the Regulatory Framework for Protein Content Claims in Canada

PubMed Central

Marinangeli, Christopher P. F.; Foisy, Samara; Shoveller, Anna K.; Porter, Cara; Musa-Veloso, Kathy; Sievenpiper, John L.; Jenkins, David J. A.

2017-01-01

The need for protein-rich plant-based foods continues as dietary guidelines emphasize their contribution to healthy dietary patterns that prevent chronic disease and promote environmental sustainability. However, the Canadian Food and Drug Regulations provide a regulatory framework that can prevent Canadian consumers from identifying protein-rich plant-based foods. In Canada, protein nutrient content claims are based on the protein efficiency ratio (PER) and protein rating method, which is based on a rat growth bioassay. PERs are not additive, and the protein rating of a food is underpinned by its Reasonable Daily Intake. The restrictive nature of Canada’s requirements for supporting protein claims therefore presents challenges for Canadian consumers to adapt to a rapidly changing food environment. This commentary will present two options for modernizing the regulatory framework for protein content claims in Canada. The first and preferred option advocates that protein quality not be considered in the determination of the eligibility of a food for protein content claims. The second and less preferred option, an interim solution, is a framework for adopting the protein digestibility corrected amino acid score as the official method for supporting protein content and quality claims and harmonizes Canada’s regulatory framework with that of the USA. PMID:28832556

Toxicogenomics and the Regulatory Framework

EPA Science Inventory

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

[Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research and commentary].

PubMed

Shichinohe, Toshiaki; Kondo, Satoshi; Ide, Chizuka; Higuchi, Norio; Aiso, Sadakazu; Sakai, Tatsuo; Matsumura, George; Yoshida, Kazunari; Kobayashi, Eiji; Tatsumi, Haruyuki; Yaginuma, Hiroyuki; Hishikawa, Shuji; Sugimoto, Maki; Izawa, Yoshimitsu; Imanishi, Nobuaki

2011-07-01

This article analyses the Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research drawn by the Study Group for Future Training Systems of Surgical Skills and Procedures established by the Fiscal Year 2010 research program of the Ministry of Health, Labor and Welfare. The purpose of the Draft of Guidelines is: First, to lay out the required basic guidelines for human cadaver usage to allow medical and dental faculty to conduct clinical education and research in accordance with existing regulations. Second, the guidelines are expected to give physicians a regulatory framework to carry out cadaver training in accordance with the current legal framework. This article explains the Draft of Guidelines in detail, outlines the future of cadaver training, and describes issues which must still be solved.

[Draft of guidelines for human body dissection for clinical anatomy education and research and commentary].

PubMed

Shichinohe, Toshiaki; Kondo, Satoshi; Ide, Chizuka; Higuchi, Norio; Aiso, Sadakazu; Sakai, Tatsuo; Matsumura, George; Yoshida, Kazunari; Kobayashi, Eiji; Tatsumi, Haruyuki; Yaginuma, Hiroyuki; Hishikawa, Shuji; Sugimoto, Maki; Izawa, Yoshimitsu; Imanishi, Nobuaki

2011-06-01

This article analyses the Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research drawn by the Study Group for Future Training Systems of Surgical Skills and Procedures established by the Fiscal Year 2010 research program of the Ministry of Health, Labor and Welfare. The purpose of the Draft of Guidelines is: First, to lay out the required basic guidelines for human cadaver usage to allow medical and dental faculty to conduct clinical education and research in accordance with existing regulations. Second, the guidelines are expected to give physicians a regulatory framework to carry out cadaver training in accordance with the current legal framework. This article explains the Draft of Guidelines in detail, outlines the future of cadaver training, and describes issues which must still be solved.

Extended evolution: A conceptual framework for integrating regulatory networks and niche construction

PubMed Central

Renn, Jürgen

2015-01-01

ABSTRACT This paper introduces a conceptual framework for the evolution of complex systems based on the integration of regulatory network and niche construction theories. It is designed to apply equally to cases of biological, social and cultural evolution. Within the conceptual framework we focus especially on the transformation of complex networks through the linked processes of externalization and internalization of causal factors between regulatory networks and their corresponding niches and argue that these are an important part of evolutionary explanations. This conceptual framework extends previous evolutionary models and focuses on several challenges, such as the path‐dependent nature of evolutionary change, the dynamics of evolutionary innovation and the expansion of inheritance systems. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 565–577, 2015. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc. PMID:26097188

[Advanced therapy: from European regulatory framework to national regulatory framework].

PubMed

Lucas-Samuel, S

2013-05-01

The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012. Copyright © 2013. Published by Elsevier SAS.

Long-Term Management Strategy for Dredged Material Disposal for Naval Weapons Station, Yorktown, Yorktown, Virginia; Naval Supply Center, Cheatham Annex, Williamsburg, Virginia; and Naval Amphibious Base, Little Creek, Norfolk, Virginia. Phase 2: Formulation of Alternatives

DTIC Science & Technology

1993-03-01

Regulatory Framework and Management Strategy ... .......... 11 Need for Criteria ............... ........................ .. 12 Criteria for Open-Water... Framework and Managetent Strategy 19. Because the Phase I results indicated that there is insufficient confined disposal capacity, the assessment of open...regulatory framework established for Sections 103 and 404. 11 20. All disposal options considered for this LTMS were examined using the Corps Management

Commercialization of genetic testing services: the FDA, market forces, and biological tarot cards.

PubMed

Malinowski, M J; Blatt, R J R

1997-03-01

Many women fear being diagnosed with breast cancer, and rightfully so. Despite the capabilities of modern medicine, the cumulative lifetime risk of getting the disease has risen to one in eight and, despite decades of research, no cures exist. In this Article, the authors explore the commercialization of so-called breast cancer gene tests, based upon genetic alterations linked to the disease. Although the authors fully address this specific technology, they use what constitutes the seminal case of predictive genetic testing to analyze the adequacy of the existing regulatory framework. The authors conclude that the present regulatory system is inadequate and places a dangerous amount of reliance on primary care physicians. Their conclusion is grounded in the observation that most primary care physicians lack sufficient knowledge about this evolving investigative technology--which is highly subject to misinterpretation, and, though potentially helpful to some "high risk" patients, offers questionable clinical value for the general public. The authors set forth numerous proposals to promote both the quality and clinical value of predictive genetic testing so that it conforms to public health standards and can be properly integrated as a reliable component of medical care in specific situations.

Regulation and oversight of independent health facilities in Canada.

PubMed

Pries, Charlene R; Vanin, Sharon; Cartagena, Rosario G

2014-02-01

Independent health facilities ("IHFs") are an important part of Canada's health care system existing at the interface of public and private care. They offer benefits to individual patients and the public at large, such as improved access to care, reduced wait times, improved choice in the delivery of care, and more efficient use of health care resources. They can also provide physicians greater autonomy, control of resources, and opportunity for profit compared to other practice settings, particularly because IHFs can deliver services outside of publicly-funded health care plans. IHFs also present challenges, particularly around quality of care and patient safety, and the potential to breach the principles of "Medicare" under the Canada Health Act. Various measures are in place to address these challenges, while still enabling the benefits IHFs can offer. IHFs are primarily regulated and overseen at the provincial level through legislation, regulations and provincial medical regulatory College by-laws. Health Canada is responsible for administering the overarching framework for "Medicare". Oversight and regulatory provisions vary across Canada, and are notably absent in the Maritime provinces and the territories. This article provides an overview of specific provisions related to IHFs across the country and how they can co-exist with the Canada Health Act.

Risk-based requirements management framework with applications to assurance cases

NASA Astrophysics Data System (ADS)

Feng, D.; Eyster, C.

The current regulatory approach for assuring device safety primarily focuses on compliance with prescriptive safety regulations and relevant safety standards. This approach, however, does not always lead to a safe system design even though safety regulations and standards have been met. In the medical device industry, several high profile recalls involving infusion pumps have prompted the regulatory agency to reconsider how device safety should be managed, reviewed and approved. An assurance case has been cited as a promising tool to address this growing concern. Assurance cases have been used in safety-critical systems for some time. Most assurance cases, if not all, in literature today are developed in an ad hoc fashion, independent from risk management and requirement development. An assurance case is a resource-intensive endeavor that requires additional effort and documentation from equipment manufacturers. Without a well-organized requirements infrastructure in place, such “ additional effort” can be substantial, to the point where the cost of adoption outweighs the benefit of adoption. In this paper, the authors present a Risk-Based Requirements and Assurance Management (RBRAM) methodology. The RBRAM is an elaborate framework that combines Risk-Based Requirements Management (RBRM) with assurance case methods. Such an integrated framework can help manufacturers leverage an existing risk management to present a comprehensive assurance case with minimal additional effort while providing a supplementary means to reexamine the integrity of the system design in terms of the mission objective. Although the example used is from the medical industry, the authors believe that the RBRAM methodology underlines the fundamental principle of risk management, and offers a simple, yet effective framework applicable to aerospace industry, perhaps, to any industry.

Conflict of interest in biomedical research: a view from Europe.

PubMed

Salvi, Maurizio

2003-01-01

In this paper I address the conflict of interest (CoI) issue from a legal point of view at a European level. We will see that the regulatory framework that exists in Europe does state the need for the independence of ethics committee involved in authorisation of research and clinical trials. We will see that CoI is an element that has to be closely monitored at National and International level. Therefore, Member States and Newly Associated States do have to address CoI in the authorisation process of research and clinical protocols of biomedicine.

State Regulatory Authority (SRA) Coordination of Safety, Security, and Safeguards of Nuclear Facilities: A Framework for Analysis

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

Mladineo, Stephen V.; Frazar, Sarah L.; Kurzrok, Andrew J.

This paper will explore the development of a framework for conducting an assessment of safety-security-safeguards integration within a State. The goal is to examine State regulatory structures to identify conflicts and gaps that hinder management of the three disciplines at nuclear facilities. Such an analysis could be performed by a State Regulatory Authority (SRA) to provide a self-assessment or as part of technical cooperation with either a newcomer State, or to a State with a fully developed SRA.

JCell--a Java-based framework for inferring regulatory networks from time series data.

PubMed

Spieth, C; Supper, J; Streichert, F; Speer, N; Zell, A

2006-08-15

JCell is a Java-based application for reconstructing gene regulatory networks from experimental data. The framework provides several algorithms to identify genetic and metabolic dependencies based on experimental data conjoint with mathematical models to describe and simulate regulatory systems. Owing to the modular structure, researchers can easily implement new methods. JCell is a pure Java application with additional scripting capabilities and thus widely usable, e.g. on parallel or cluster computers. The software is freely available for download at http://www-ra.informatik.uni-tuebingen.de/software/JCell.

Evidence-based causation in toxicology: A 10-year retrospective.

PubMed

James, R C; Britt, J K; Halmes, N C; Guzelian, P S

2015-12-01

We introduced Evidence-based Toxicology (EBT) in 2005 to address the disparities that exist between the various Weight-of-Evidence (WOE) methods typically applied in the regulatory hazard decision-making arena and urged toxicologists to adopt the evidence-based guidelines long-utilized in medicine (i.e., Evidence-Based Medicine or EBM). This review of the activities leading to the adoption of evidence-based methods and EBT during the last decade demonstrates how fundamental concepts that form EBT, such as the use of systematic reviews to capture and consider all available information, are improving toxicological evaluations performed by various groups and agencies. We reiterate how the EBT framework, a process that provides a method for performing human chemical causation analyses in an objective, transparent and reproducible manner, differs significantly from past and current regulatory WOE approaches. We also discuss why the uncertainties associated with regulatory WOE schemes lead to a definition of the term "risk" that contains unquantifiable uncertainties not present in this term as it is used in epidemiology and medicine. We believe this distinctly different meaning of "risk" should be clearly conveyed to those not familiar with this difference (e.g., the lay public), when theoretical/nomologic risks associated with chemical-induced toxicities are presented outside of regulatory and related scientific parlance. © The Author(s) 2015.

A strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece.

PubMed

Petri, Aspasia; Karabetsos, Efthymios

2018-06-08

Herein, the strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece is presented. This framework has been designed and promoted by the competent national regulatory authority, which is the Greek Atomic Energy Commission (EEAE). The aim is to ensure a common understanding regarding ultraviolet radiation (UVR) and artificial tanning among the artificial tanning professionals, the stakeholders and the general public. The strategic framework is founded on the international organizations' recommendations, the EU requirements and the relevant technical standards. It is comprised of three autonomous but interconnected components: A) A sunbed operators' e-training course and certification process, B) A code of practice addressed individually to the business owners, the sunbeds operators and the sunbeds users, C) Communication strategies aiming to raise awareness regarding UVR and artificial tanning to all the interested parties. The artificial tanning safety culture framework presented here is the policy option that EEAE undertook and it is embedded in the upcoming legislation and regulations for the provision of artificial tanning services in Greece. EEAE considers that the structure of the artificial tanning safety culture strategic framework will serve as the guide for the development and promotion of relevant safety culture strategic frameworks for the provision of aesthetic/wellness services that utilize other non-ionizing radiation sources, which currently don't exist. © 2018 IOP Publishing Ltd.

Computational methods in sequence and structure prediction

NASA Astrophysics Data System (ADS)

Lang, Caiyi

This dissertation is organized into two parts. In the first part, we will discuss three computational methods for cis-regulatory element recognition in three different gene regulatory networks as the following: (a) Using a comprehensive "Phylogenetic Footprinting Comparison" method, we will investigate the promoter sequence structures of three enzymes (PAL, CHS and DFR) that catalyze sequential steps in the pathway from phenylalanine to anthocyanins in plants. Our result shows there exists a putative cis-regulatory element "AC(C/G)TAC(C)" in the upstream of these enzyme genes. We propose this cis-regulatory element to be responsible for the genetic regulation of these three enzymes and this element, might also be the binding site for MYB class transcription factor PAP1. (b) We will investigate the role of the Arabidopsis gene glutamate receptor 1.1 (AtGLR1.1) in C and N metabolism by utilizing the microarray data we obtained from AtGLR1.1 deficient lines (antiAtGLR1.1). We focus our investigation on the putatively co-regulated transcript profile of 876 genes we have collected in antiAtGLR1.1 lines. By (a) scanning the occurrence of several groups of known abscisic acid (ABA) related cisregulatory elements in the upstream regions of 876 Arabidopsis genes; and (b) exhaustive scanning of all possible 6-10 bps motif occurrence in the upstream regions of the same set of genes, we are able to make a quantative estimation on the enrichment level of each of the cis-regulatory element candidates. We finally conclude that one specific cis-regulatory element group, called "ABRE" elements, are statistically highly enriched within the 876-gene group as compared to their occurrence within the genome. (c) We will introduce a new general purpose algorithm, called "fuzzy REDUCE1", which we have developed recently for automated cis-regulatory element identification. In the second part, we will discuss our newly devised protein design framework. With this framework we have developed a software package which is capable of designing novel protein structures at the atomic resolution. This software package allows us to perform protein structure design with a flexible backbone. The backbone flexibility includes loop region relaxation as well as a secondary structure collective mode relaxation scheme. (Abstract shortened by UMI.)

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

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

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

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

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

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

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

PubMed

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.

Means and ENDS - e-cigarettes, the Framework Convention on Tobacco Control, and global health diplomacy in action.

PubMed

Russell, Andrew; Wainwright, Megan; Tilson, Melodie

2018-01-01

E-cigarettes are a new and disruptive element in global health diplomacy (GHD) and policy-making. This is an ethnographic account of how e-cigarettes and other Electronic Nicotine Delivery Systems (ENDS) were tackled at the 6th Conference of the Parties to the World Health Organization's Framework Convention on Tobacco Control. It demonstrates how uncertainty about ENDS and differences of opinion are currently so great that 'agreeing to disagree' as a consensus position and 'strategic use of time' were the principles that ensured effective GHD in this case. Observers representing accredited non-governmental organisations were active in briefing and lobbying country delegates not to spend too much time debating an issue for which insufficient evidence exists, and for which countries were unlikely to reach a consensus on a specific regulatory approach or universally applicable regulatory measures. Equally, the work of Costa Rica in preparing and re-negotiating the draft decision, and the work of the relevant Committee Chair in managing the discussion, contributed to effectively reining in lengthy statements from Parties and focusing on points of consensus. As well as summarising the debate itself and analysing the issues surrounding it, this account offers an example of GHD working effectively in a situation of epistemic uncertainty.

Analysis and Comparison of Carbon Capture & Sequestration Policies

NASA Astrophysics Data System (ADS)

Burton, E.; Ezzedine, S. M.; Reed, J.; Beyer, J. H.; Wagoner, J. L.

2010-12-01

Several states and countries have adopted or are in the process of crafting policies to enable geologic carbon sequestration projects. These efforts reflect the recognition that existing statutory and regulatory frameworks leave ambiguities or gaps that elevate project risk for private companies considering carbon sequestration projects, and/or are insufficient to address a government’s mandate to protect the public interest. We have compared the various approaches that United States’ state and federal governments have taken to provide regulatory frameworks to address carbon sequestration. A major purpose of our work is to inform the development of any future legislation in California, should it be deemed necessary to meet the goals of Assembly Bill 1925 (2006) to accelerate the adoption of cost-effective geologic sequestration strategies for the long-term management of industrial carbon dioxide in the state. Our analysis shows a diverse issues are covered by adopted and proposed carbon capture and sequestration (CCS) legislation and that many of the new laws focus on defining regulatory frameworks for underground injection of CO2, ambiguities in property issues, or assigning legal liability. While these approaches may enable the progress of early projects, future legislation requires a longer term and broader view that includes a quantified integration of CCS into a government’s overall climate change mitigation strategy while considering potentially counterproductive impacts on CCS of other climate change mitigation strategies. Furthermore, legislation should be crafted in the context of a vision for CCS as an economically viable and widespread industry. While an important function of new CCS legislation is enabling early projects, it must be kept in mind that applying the same laws or protocols in the future to a widespread CCS industry may result in business disincentives and compromise of the public interest in mitigating GHG emissions. Protection of the public interest requires that monitoring and verification track the long term fate of pipelined CO2 regardless of its end use in order to establish that climate change goals are being met.

Beyond regulatory compression: confronting the liminal spaces of health research regulation

PubMed Central

Taylor-Alexander, Samuel; Dove, Edward S.; Fletcher, Isabel; Ganguli Mitra, Agomoni; McMillan, Catriona; Laurie, Graeme

2016-01-01

ABSTRACT Biomedicine and the life sciences continuously rearrange the relationship between culture and biology. In consequence, we increasingly look for a suitable regulatory response to reduce perceived uncertainty and instability. This article examines the full implications of this ‘regulatory turn’ by drawing on the anthropological concept of liminality. We offer the term ‘regulatory compression’ to characterise the effects of extant regulatory approaches on health research practices. With its focus on transformation and the ‘in-between’, liminality allows us to see how regulatory frameworks rely on a silo-based approach to classifying and regulating research objects such that they: (1) limit the flexibility necessary in clinical and laboratory research; (2) result in the emergence of unregulated spaces that lie between the bounded regulatory spheres; and (3) curtail modes of public participation in the health research enterprise. We suggest there is a need to develop the notion of ‘processual regulation’, a novel framework that requires a temporal-spatial examination of regulatory spaces and practices as these are experienced by all actors, including the relationship of actors with the objects of regulation. PMID:28058061

Aberrant Gene Expression in Humans

PubMed Central

Yang, Ence; Ji, Guoli; Brinkmeyer-Langford, Candice L.; Cai, James J.

2015-01-01

Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating complex traits and conditions. PMID:25617623

Cosmetic Regulations: A Comparative Study.

PubMed

Suhag, Jyoti; Dureja, Harish

2015-01-01

The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

Control of fluxes in metabolic networks

PubMed Central

Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

2016-01-01

Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

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

PubMed

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

2017-01-01

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

The Regulatory Framework for Privacy and Security

NASA Astrophysics Data System (ADS)

Hiller, Janine S.

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

United States Food and Drug Administration Regulation of Gene and Cell Therapies.

PubMed

Bailey, Alexander M; Arcidiacono, Judith; Benton, Kimberly A; Taraporewala, Zenobia; Winitsky, Steve

2015-01-01

The United States (US) Food and Drug Administration (FDA) is a regulatory agency that has oversight for a wide range of products entering the US market, including gene and cell therapies. The regulatory approach for these products is similar to other medical products within the United States and consists of a multitiered framework of statutes, regulations, and guidance documents. Within this framework, there is considerable flexibility which is necessary due to the biological and technical complexity of these products in general. This chapter provides an overview of the US FDA regulatory oversight of gene and cell therapy products.

Examination of the regulatory frameworks applicable to biologic drugs (including stem cells and their progeny) in Europe, the U.S., and Australia: part I--a method of manual documentary analysis.

PubMed

Ilic, Nina; Savic, Snezana; Siegel, Evan; Atkinson, Kerry; Tasic, Ljiljana

2012-12-01

Recent development of a wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Cohort 1 of the selected 18 high-tier regulatory documents from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Therapeutic Goods Administration (TGA) regulatory frameworks were subject to a manual documentary analysis. These documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Manual analysis included a terminology search. The occurrence, frequency, and interchangeable use of different terms and phrases were recorded in the manual documentary analysis. Despite obvious differences, manual documentary analysis revealed certain consistency in use of terminology across analyzed frameworks. Phrase search frequencies have shown less uniformity than the search of terms. Overall, the EMA framework's documents referred to "medicinal products" and "marketing authorization(s)," the FDA documents discussed "drug(s)" or "biologic(s)," and the TGA documents referred to "biological(s)." Although high-tier documents often use different terminology they share concepts and themes. Documents originating from the same source have more conjunction in their terminology although they belong to different frameworks (i.e., Good Clinical Practice requirements based on the Declaration of Helsinki, 1964). Automated (software-based) documentary analysis should be obtained for the conceptual and relational analysis.

Examination of the Regulatory Frameworks Applicable to Biologic Drugs (Including Stem Cells and Their Progeny) in Europe, the U.S., and Australia: Part I—A Method of Manual Documentary Analysis

PubMed Central

Savic, Snezana; Siegel, Evan; Atkinson, Kerry; Tasic, Ljiljana

2012-01-01

Recent development of a wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Cohort 1 of the selected 18 high-tier regulatory documents from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Therapeutic Goods Administration (TGA) regulatory frameworks were subject to a manual documentary analysis. These documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Manual analysis included a terminology search. The occurrence, frequency, and interchangeable use of different terms and phrases were recorded in the manual documentary analysis. Despite obvious differences, manual documentary analysis revealed certain consistency in use of terminology across analyzed frameworks. Phrase search frequencies have shown less uniformity than the search of terms. Overall, the EMA framework's documents referred to “medicinal products” and “marketing authorization(s),” the FDA documents discussed “drug(s)” or “biologic(s),” and the TGA documents referred to “biological(s).” Although high-tier documents often use different terminology they share concepts and themes. Documents originating from the same source have more conjunction in their terminology although they belong to different frameworks (i.e., Good Clinical Practice requirements based on the Declaration of Helsinki, 1964). Automated (software-based) documentary analysis should be obtained for the conceptual and relational analysis. PMID:23283551

Frameworks and tools for risk assessment of manufactured nanomaterials.

PubMed

Hristozov, Danail; Gottardo, Stefania; Semenzin, Elena; Oomen, Agnes; Bos, Peter; Peijnenburg, Willie; van Tongeren, Martie; Nowack, Bernd; Hunt, Neil; Brunelli, Andrea; Scott-Fordsmand, Janeck J; Tran, Lang; Marcomini, Antonio

2016-10-01

Commercialization of nanotechnologies entails a regulatory requirement for understanding their environmental, health and safety (EHS) risks. Today we face challenges to assess these risks, which emerge from uncertainties around the interactions of manufactured nanomaterials (MNs) with humans and the environment. In order to reduce these uncertainties, it is necessary to generate sound scientific data on hazard and exposure by means of relevant frameworks and tools. The development of such approaches to facilitate the risk assessment (RA) of MNs has become a dynamic area of research. The aim of this paper was to review and critically analyse these approaches against a set of relevant criteria. The analysis concluded that none of the reviewed frameworks were able to fulfill all evaluation criteria. Many of the existing modelling tools are designed to provide screening-level assessments rather than to support regulatory RA and risk management. Nevertheless, there is a tendency towards developing more quantitative, higher-tier models, capable of incorporating uncertainty into their analyses. There is also a trend towards developing validated experimental protocols for material identification and hazard testing, reproducible across laboratories. These tools could enable a shift from a costly case-by-case RA of MNs towards a targeted, flexible and efficient process, based on grouping and read-across strategies and compliant with the 3R (Replacement, Reduction, Refinement) principles. In order to facilitate this process, it is important to transform the current efforts on developing databases and computational models into creating an integrated data and tools infrastructure to support the risk assessment and management of MNs. Copyright © 2016 Elsevier Ltd. All rights reserved.

A framework to analyze emissions implications of ...

EPA Pesticide Factsheets

Future year emissions depend highly on the evolution of the economy, technology and current and future regulatory drivers. A scenario framework was adopted to analyze various technology development pathways and societal change while considering existing regulations and future uncertainty in regulations and evaluate resulting emissions growth patterns. The framework integrates EPA’s energy systems model with an economic Input-Output (I/O) Life Cycle Assessment model. The EPAUS9r MARKAL database is assembled from a set of technologies to represent the U.S. energy system within MARKAL bottom-up technology rich energy modeling framework. The general state of the economy and consequent demands for goods and services from these sectors are taken exogenously in MARKAL. It is important to characterize exogenous inputs about the economy to appropriately represent the industrial sector outlook for each of the scenarios and case studies evaluated. An economic input-output (I/O) model of the US economy is constructed to link up with MARKAL. The I/O model enables user to change input requirements (e.g. energy intensity) for different sectors or the share of consumer income expended on a given good. This gives end-users a mechanism for modeling change in the two dimensions of technological progress and consumer preferences that define the future scenarios. The framework will then be extended to include environmental I/O framework to track life cycle emissions associated

Multicriteria mapping of stakeholder preferences in regulating nanotechnology

NASA Astrophysics Data System (ADS)

Hansen, Steffen Foss

2010-08-01

In order to facilitate stakeholder discussions on how to regulate nanotechnology, the opensource program multicriteria mapping (MCM) was used to structure 26 interviews with stakeholders in the USA. MCM offers a systematic part quantitative, part qualitative approach to clarify why some regulatory options (bans, moratoriums, voluntary measures, etc.) were deemed to be acceptable/unacceptable by various stakeholders and which criteria stakeholders used to evaluate the different regulatory options. Adopting an incremental approach and implementing a new regulatory framework was evaluated as the best options whereas a complete ban and no additional regulation of nanotechnology were found to be the least favorable. Criteria applied differed substantially among stakeholders and included social, ethical, regulatory, environmental, and health issues. Opinions on future regulation seem far less polarized than expected and it seems that stakeholders would welcome a combination of voluntary measures, an incremental approach and forming of a new regulatory framework.

Regulating assisted reproductive technologies in Victoria: the impact of changing policy concerning the accessibility of in vitro fertilisation for preimplantation tissue-typing.

PubMed

Smith, Malcolm K

2012-06-01

On 1 January 2010, the Assisted Reproductive Treatment Act 2008 (Vic) came into force. The legislation was the outcome of a detailed review and consultation process undertaken by the Victorian Law Reform Commission. Arguably, the change to the regulatory framework represents a significant shift in policy compared to previous regulatory approaches on this topic in Victoria. This article considers the impact of the new legislation on eligibility for reproductive treatments, focusing on the accessibility of such services for the purpose of creating a "saviour sibling". It also highlights the impact of the Victorian regulatory body's decision to abolish its regulatory policies on preimplantation genetic diagnosis and preimplantation tissue-typing, concluding that the regulatory approach in relation to these latter issues is similar to other Australian jurisdictions where such practices are not addressed by a statutory framework.

Current challenges in bioequivalence, quality, and novel assessment technologies for topical products.

PubMed

Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D; Benfeldt, Eva; Davit, Barbara; Ganes, Derek; Ghosh, Tapash; Kanfer, Isadore; Kasting, Gerald B; Katz, Lindsey; Lionberger, Robert; Lu, Guang Wei; Maibach, Howard I; Pershing, Lynn K; Rackley, Russell J; Raw, Andre; Shukla, Chinmay G; Thakker, Kailas; Wagner, Nathalie; Zovko, Elizabeta; Lane, Majella E

2014-04-01

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed. The outcome of the workshop emphasized both a need for greater attention to quality, possibly, via a Quality-By-Design (QBD) approach and a need to develop a "whole toolkit" approach towards the problem of determination of rate and extent in the assessment of topical bioavailability. The discussion on the BE and clinical equivalence of topical products revealed considerable concerns about the variability present in the current methodologies utilized by the industry and regulatory agencies. It was proposed that academicians, researchers, the pharmaceutical industry and regulators work together to evaluate and validate alternative methods that are based on both the underlying science and are adapted to the drug product itself instead of single "universal" method.

Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

PubMed Central

Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain

2009-01-01

Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955

Chemical contaminants entering the marine environment from sea-based sources: A review with a focus on European seas.

PubMed

Tornero, Victoria; Hanke, Georg

2016-11-15

Anthropogenic contaminants reach the marine environment mostly directly from land-based sources, but there are cases in which they are emitted or re-mobilized in the marine environment itself. This paper reviews the literature, with a predominant focus on the European environment, to compile a list of contaminants potentially released into the sea from sea-based sources and provide an overview of their consideration under existing EU regulatory frameworks. The resulting list contains 276 substances and for some of them (22 antifouling biocides, 32 aquaculture medicinal products and 34 warfare agents) concentrations and toxicity data are additionally provided. The EU Marine Strategy Framework Directive Descriptor 8, together with the Water Framework Directive and the Regional Sea Conventions, provides the provisions against pollution of marine waters by chemical substances. This literature review should inform about the current state of knowledge regarding marine contaminant sources and provide support for setting-up of monitoring approaches, including hotspots screening. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

PubMed

Vandenberg, Laura N; Ågerstrand, Marlene; Beronius, Anna; Beausoleil, Claire; Bergman, Åke; Bero, Lisa A; Bornehag, Carl-Gustaf; Boyer, C Scott; Cooper, Glinda S; Cotgreave, Ian; Gee, David; Grandjean, Philippe; Guyton, Kathryn Z; Hass, Ulla; Heindel, Jerrold J; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Macleod, Malcolm R; Martin, Olwenn V; Norinder, Ulf; Scheringer, Martin; Thayer, Kristina A; Toppari, Jorma; Whaley, Paul; Woodruff, Tracey J; Rudén, Christina

2016-07-14

The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

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

PubMed

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

2013-09-01

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

Comparison of international food allergen labeling regulations.

PubMed

Gendel, Steven M

2012-07-01

Food allergy is a significant public health issue worldwide. Regulatory risk management strategies for allergic consumers have focused on providing information about the presence of food allergens through label declarations. A number of countries and regulatory bodies have recognized the importance of providing this information by enacting laws, regulations or standards for food allergen labeling of "priority allergens". However, different governments and organizations have taken different approaches to identifying these "priority allergens" and to designing labeling declaration regulatory frameworks. The increasing volume of the international food trade suggests that there would be value in supporting sensitive consumers by harmonizing (to the extent possible) these regulatory frameworks. As a first step toward this goal, an inventory of allergen labeling regulations was assembled and analyzed to identify commonalities, differences, and future needs. Published by Elsevier Inc.

What should a radiation regulator do about naturally occurring radioactive material?

PubMed

Loy, J

2015-06-01

The standard regulatory framework of authorisation, review and assessment, inspection and enforcement, and regulation making is directed principally towards ensuring the regulatory control of planned exposure situations. Some mining and industrial activities involving exposures to naturally occurring radioactive material (NORM), such as uranium mining or the treatment and conditioning of NORM residues, may fit readily within this standard framework. In other cases, such as oil and gas exploration and production, the standard regulatory framework needs to be adjusted. For example, it is not sensible to require that an oil company seek a licence from the radiation regulator before drilling a well. The paper discusses other approaches that a regulator might take to assure protection and safety in such activities involving exposures to NORM, including the use of conditional exemptions from regulatory controls. It also suggests some areas where further guidance from the International Commission on Radiological Protection on application of the system of radiological protection to NORM would assist both regulators and operators. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

PubMed

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

2011-05-01

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

78 FR 32686 - Final Supplemental Environmental Impact Statement on the Issuance of Annual Regulations...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-31

... process. (2) Frequency of review and adoption of duck regulatory packages. Duck regulatory packages are the set of framework regulations that apply to the general duck hunting seasons. Packages include..., we present two alternatives regarding how frequently duck regulatory packages should be reviewed and...

Economic regulation of ambulance services in California.

PubMed

Narad, R A

1997-01-01

This study was intended to identify economic regulatory programs used by California counties (including ambulance franchising and rate setting), to inventory their foci and application, and to identify differences around the state. By studying the variety of programs used in one state, this study establishes a framework for evaluation of state and local regulatory programs elsewhere. This study surveyed all California local EMS agencies (LEMSAs); these are California's equivalent of regional EMS organizations. The survey achieved a 100% response rate, and all data involve population parameters obviating the need for inferential statistics. Seventy-three percent of California counties use economic regulations. Large-population counties and those that operate their own LEMSAs are more likely to use economic regulations than are small counties and those that participate in multicounty EMS agencies. Despite a preference for competition in the authorizing statute, most franchises were granted without competition to existing providers. The majority of franchises in the state were granted to public services. Most ambulance rate setting occurs outside of a competitive process. Economic regulations that were intended to provide a structured marketplace are often being used to protect existing providers, particularly public services, from competition. The growing interest by fire departments in entering the market for emergency ambulance service, along with the existing bias toward them in granting of franchises, does not bode well for use of the competitive process. The growth of managed care may change or eliminate the need for economic regulations but, if they are to continue, more state oversight should be considered.

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

PubMed

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

2018-05-08

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

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

Metzler, D.; Gibb, J.P.; Glover, W.A.

Compliance with the mandate of the Uranium Mill Tailings Radiation Control Act (UMTRCA) at Uranium Mill Tailings Remedial Action (UMTRA) Project sites requires implementation of a groundwater remedial action plan that meets the requirements of Subpart B of the US Environmental Protection Agency`s proposed groundwater protection standards (40 CFR 192). The UMTRA Groundwater Project will ensure that unacceptable current risk or potential risk to the public health, safety and the environment resulting from the groundwater contamination attributable to the UMTRA sites, is mitigated in a timely and cost-efficient manner. For each UMTRA processing site and vicinity property where contamination exists,more » a groundwater remedial action plan must be developed that identifies hazardous constituents and establishes acceptable concentration limits for the hazardous constituents as either (a) alternate concentration limits (ACL), (b) maximum concentration limits (MCLs), (c) supplemental standards, or (d) background groundwater quality levels. Project optimization is a strategy that will aggressively work within the current regulatory framework using all available options to meet regulatory requirements. This strategy is outlined within.« less

PathCase-SB architecture and database design

PubMed Central

2011-01-01

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

Application of Framework for Integrating Safety, Security and Safeguards (3Ss) into the Design Of Used Nuclear Fuel Storage Facility

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

Badwan, Faris M.; Demuth, Scott F

Department of Energy’s Office of Nuclear Energy, Fuel Cycle Research and Development develops options to the current commercial fuel cycle management strategy to enable the safe, secure, economic, and sustainable expansion of nuclear energy while minimizing proliferation risks by conducting research and development focused on used nuclear fuel recycling and waste management to meet U.S. needs. Used nuclear fuel is currently stored onsite in either wet pools or in dry storage systems, with disposal envisioned in interim storage facility and, ultimately, in a deep-mined geologic repository. The safe management and disposition of used nuclear fuel and/or nuclear waste is amore » fundamental aspect of any nuclear fuel cycle. Integrating safety, security, and safeguards (3Ss) fully in the early stages of the design process for a new nuclear facility has the potential to effectively minimize safety, proliferation, and security risks. The 3Ss integration framework could become the new national and international norm and the standard process for designing future nuclear facilities. The purpose of this report is to develop a framework for integrating the safety, security and safeguards concept into the design of Used Nuclear Fuel Storage Facility (UNFSF). The primary focus is on integration of safeguards and security into the UNFSF based on the existing Nuclear Regulatory Commission (NRC) approach to addressing the safety/security interface (10 CFR 73.58 and Regulatory Guide 5.73) for nuclear power plants. The methodology used for adaptation of the NRC safety/security interface will be used as the basis for development of the safeguards /security interface and later will be used as the basis for development of safety and safeguards interface. Then this will complete the integration cycle of safety, security, and safeguards. The overall methodology for integration of 3Ss will be proposed, but only the integration of safeguards and security will be applied to the design of the UNFSF. The framework for integration of safeguards and security into the UNFSF will include 1) identification of applicable regulatory requirements, 2) selection of a common system that share dual safeguard and security functions, 3) development of functional design criteria and design requirements for the selected system, 4) identification and integration of the dual safeguards and security design requirements, and 5) assessment of the integration and potential benefit.« less

Child Sexual Abuse in Zimbabwe.

PubMed

Mantula, Fennie; Saloojee, Haroon

2016-01-01

Although child sexual abuse is a significant public health problem globally, its incidence, prevention, and management is less well described in resource-poor settings. In poorer settings prevention initiatives assume even more importance since resources for managing abused children are severely limited. This article examines the current status of policy and practice related to the prevention of child sexual abuse in Zimbabwe. It identifies implementation challenges and highlights opportunities that could be embraced to reduce CSA in Zimbabwe, based on evidence synthesized from recent work. Although Zimbabwe has a well-established legal and regulatory framework to protect children from child sexual abuse, implementation of existing policies is weak. Financial, human, and material resource constraints are frequently cited to explain limited prevention activity. Effective strategies for the prevention of child sexual abuse should focus on implementing existing legislation, targeting schoolchildren, and getting community involvement. A dedicated budget would help entrench these strategies, but gains can be achieved even in the absence of this.

75 FR 39577 - Draft Supplemental Environmental Impact Statement on the Issuance of Annual Regulations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... timing of the general regulatory process. (2) Frequency of review and adoption of duck regulatory packages. Duck regulatory packages are the set of framework regulations that apply to the general duck... limits), and closed. In the draft SEIS, we present two alternatives regarding how frequently duck...

Guidelines for Bacteriophage Product Certification.

PubMed

Fauconnier, Alan

2018-01-01

Following decades in the wilderness, bacteriophage therapy is now appearing as a credible antimicrobial strategy. However, this reemerging therapy does not rekindle without raising sensitive regulatory concerns. Indeed, whereas the European regulatory framework has been basically implemented to tackle ready-to-use pharmaceuticals produced on a large scale, bacteriophage therapy relies on a dynamic approach requiring a regulation on personalized medicine, nonexistent at present. Because of this, no guideline are currently available for addressing the scientific and regulatory issues specifically related to phage therapy medicinal products (PTMP).Pending to the implementation of an appropriate regulatory framework and to the development of ensuing guidelines, several avenues which might lead to PTMP regulatory compliance are explored here. Insights might come from the multi-strain dossier approach set up for particular animal vaccines, from the homologous group concept developed for the allergen products or from the licensing process for veterinary autogenous vaccines. Depending on national legislations, customized preparations prescribed as magistral formulas or to be used on a named-patient basis are possible regulatory approaches to be considered. However, these schemes are not optimal and should thus be regarded as transitional.

A Framework for Incorporating Patient Preferences Regarding Benefits and Risks into Regulatory Assessment of Medical Technologies.

PubMed

Ho, Martin; Saha, Anindita; McCleary, K Kimberly; Levitan, Bennett; Christopher, Stephanie; Zandlo, Kristen; Braithwaite, R Scott; Hauber, A Brett

In response to 2012 guidance in which the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) stated the importance of patient-centric measures in regulatory benefit-risk assessments, the Medical Device Innovation Consortium (MDIC) initiated a project. The project was used to develop a framework to help the Food and Drug Administration (FDA) and industry sponsors understand how patient preferences regarding benefit and risk might be integrated into the review of innovative medical devices. A public-private partnership of experts from medical device industry, government, academia and non-profits collaborated on development of the MDIC patient centered benefit-risk framework. The MDIC Framework examines what patient preference information is and the potential use and value of patient preference information in the regulatory process and across the product development life cycle. The MDIC Framework also includes a catalog of patient preference assessment methods and an agenda for future research to advance the field. This article discusses key concepts in patient preference assessment of particular importance for regulators and researchers that are addressed in the MDIC Framework for patient centered benefit-risk assessment as well as the unique public-private collaboration that led its development. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Call for a dedicated European legal framework for bacteriophage therapy.

PubMed

Verbeken, Gilbert; Pirnay, Jean-Paul; Lavigne, Rob; Jennes, Serge; De Vos, Daniel; Casteels, Minne; Huys, Isabelle

2014-04-01

The worldwide emergence of antibiotic resistances and the drying up of the antibiotic pipeline have spurred a search for alternative or complementary antibacterial therapies. Bacteriophages are bacterial viruses that have been used for almost a century to combat bacterial infections, particularly in Poland and the former Soviet Union. The antibiotic crisis has triggered a renewed clinical and agricultural interest in bacteriophages. This, combined with new scientific insights, has pushed bacteriophages to the forefront of the search for new approaches to fighting bacterial infections. But before bacteriophage therapy can be introduced into clinical practice in the European Union, several challenges must be overcome. One of these is the conceptualization and classification of bacteriophage therapy itself and the extent to which it constitutes a human medicinal product regulated under the European Human Code for Medicines (Directive 2001/83/EC). Can therapeutic products containing natural bacteriophages be categorized under the current European regulatory framework, or should this framework be adapted? Various actors in the field have discussed the need for an adapted (or entirely new) regulatory framework for the reintroduction of bacteriophage therapy in Europe. This led to the identification of several characteristics specific to natural bacteriophages that should be taken into consideration by regulators when evaluating bacteriophage therapy. One important consideration is whether bacteriophage therapy development occurs on an industrial scale or a hospital-based, patient-specific scale. More suitable regulatory standards may create opportunities to improve insights into this promising therapeutic approach. In light of this, we argue for the creation of a new, dedicated European regulatory framework for bacteriophage therapy.

Regulatory guidelines for biosimilars in Malaysia.

PubMed

Abas, Arpah

2011-09-01

The biosimilars sector continues to attract huge interest and controversy. Biosimilars are new biopharmaceuticals that are "similar" but not identical to the innovator product. Characteristics of biopharmaceuticals are closely related to the manufacturing process, which implies that the products cannot be exactly duplicated. Minuscule differences in the product's structure and manufacturing process can result in different clinical outcome. This raises concerns over the safety, efficacy and even pharmacovigilance of biosimilars. Thus, biosimilars are unique - they are not a true chemical generic and are regulated via a distinct regulatory framework. This report discusses the features of Malaysian regulatory oversight of biosimilars and experience acquired in the evaluation of some products from various countries. Ensuring regulatory position adequately reflects scientific advancement, expertise/resources is key. The regulatory situation is an evolving process. Various guidance documents are being prepared with the aim of developing a uniform global framework towards assuring the dual goal of lower costs and patient safety while expediting the availability of important biosimilar products. Copyright © 2011. Published by Elsevier Ltd.

Multicriteria mapping of stakeholder preferences in regulating nanotechnology.

PubMed

Hansen, Steffen Foss

2010-08-01

In order to facilitate stakeholder discussions on how to regulate nanotechnology, the opensource program multicriteria mapping (MCM) was used to structure 26 interviews with stakeholders in the USA. MCM offers a systematic part quantitative, part qualitative approach to clarify why some regulatory options (bans, moratoriums, voluntary measures, etc.) were deemed to be acceptable/unacceptable by various stakeholders and which criteria stakeholders used to evaluate the different regulatory options. Adopting an incremental approach and implementing a new regulatory framework was evaluated as the best options whereas a complete ban and no additional regulation of nanotechnology were found to be the least favorable. Criteria applied differed substantially among stakeholders and included social, ethical, regulatory, environmental, and health issues. Opinions on future regulation seem far less polarized than expected and it seems that stakeholders would welcome a combination of voluntary measures, an incremental approach and forming of a new regulatory framework. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11051-010-0006-3) contains supplementary material, which is available to authorized users.

Analysis of functional importance of binding sites in the Drosophila gap gene network model.

PubMed

Kozlov, Konstantin; Gursky, Vitaly V; Kulakovskiy, Ivan V; Dymova, Arina; Samsonova, Maria

2015-01-01

The statistical thermodynamics based approach provides a promising framework for construction of the genotype-phenotype map in many biological systems. Among important aspects of a good model connecting the DNA sequence information with that of a molecular phenotype (gene expression) is the selection of regulatory interactions and relevant transcription factor bindings sites. As the model may predict different levels of the functional importance of specific binding sites in different genomic and regulatory contexts, it is essential to formulate and study such models under different modeling assumptions. We elaborate a two-layer model for the Drosophila gap gene network and include in the model a combined set of transcription factor binding sites and concentration dependent regulatory interaction between gap genes hunchback and Kruppel. We show that the new variants of the model are more consistent in terms of gene expression predictions for various genetic constructs in comparison to previous work. We quantify the functional importance of binding sites by calculating their impact on gene expression in the model and calculate how these impacts correlate across all sites under different modeling assumptions. The assumption about the dual interaction between hb and Kr leads to the most consistent modeling results, but, on the other hand, may obscure existence of indirect interactions between binding sites in regulatory regions of distinct genes. The analysis confirms the previously formulated regulation concept of many weak binding sites working in concert. The model predicts a more or less uniform distribution of functionally important binding sites over the sets of experimentally characterized regulatory modules and other open chromatin domains.

The Misguided Regulation of Cardiac Emergencies

PubMed Central

Traverse, Jay H

2016-01-01

The increasing regulatory burden and cost of doing clinical trials in cardiac emergencies has greatly impacted the development of novel therapies resulting in increased morbidity and mortality of patients. A new regulatory framework is required. PMID:27789585

The application of quantitative risk assessment to microbial food safety risks.

PubMed

Jaykus, L A

1996-01-01

Regulatory programs and guidelines for the control of foodborne microbial agents have existed in the U.S. for nearly 100 years. However, increased awareness of the scope and magnitude of foodborne disease, as well as the emergence of previously unrecognized human pathogens transmitted via the foodborne route, have prompted regulatory officials to consider new and improved strategies to reduce the health risks associated with pathogenic microorganisms in foods. Implementation of these proposed strategies will involve definitive costs for a finite level of risk reduction. While regulatory decisions regarding the management of foodborne disease risk have traditionally been done with the aid of the scientific community, a formal conceptual framework for the evaluation of health risks from pathogenic microorganisms in foods is warranted. Quantitative risk assessment (QRA), which is formally defined as the technical assessment of the nature and magnitude of a risk caused by a hazard, provides such a framework. Reproducing microorganisms in foods present a particular challenge to QRA because both their introduction and numbers may be affected by numerous factors within the food chain, with all of these factors representing significant stages in food production, handling, and consumption, in a farm-to-table type of approach. The process of QRA entails four designated phases: (1) hazard identification, (2) exposure assessment, (3) dose-response assessment, and (4) risk characterization. Specific analytical tools are available to accomplish the analyses required for each phase of the QRA. The purpose of this paper is to provide a description of the conceptual framework for quantitative microbial risk assessment within the standard description provided by the National Academy of Sciences (NAS) paradigm. Each of the sequential steps in QRA are discussed in detail, providing information on current applications, tools for conducting the analyses, and methodological and/or data limitations to date. Conclusions include a brief discussion of subsequent uncertainty and risk analysis methodologies, and a commentary on present and future applications of QRA in the management of the public health risks associated with the presence of pathogenic microorganisms in the food supply.

78 FR 16341 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

... regulatory regime applicable to the over-the-counter derivatives markets. Title VII provides the SEC and the CFTC with tools to oversee these markets.\\4\\ Under the comprehensive framework established in Title VII... Rule),\\11\\ arising from the daily mark to market of the CDS (``variation margin''). FINRA notes that...

A Holistic Framework for Environmental Flows Determination in Hydropower Contexts

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

McManamay, Ryan A; Bevelhimer, Mark S

2013-05-01

Among the ecological science community, the consensus view is that the natural flow regime sustains the ecological integrity of river systems. This prevailing viewpoint by many environmental stakeholders has progressively led to increased pressure on hydropower dam owners to change plant operations to affect downstream river flows with the intention of providing better conditions for aquatic biological communities. Identifying the neccessary magnitude, frequency, duration, timing, or rate of change of stream flows to meet ecological needs in a hydropower context is challenging because the ecological responses to changes in flows may not be fully known, there are usually a multitudemore » of competing users of flow, and implementing environmental flows usually comes at a price to energy production. Realistically, hydropower managers must develop a reduced set of goals that provide the most benefit to the identified ecological needs. As a part of the Department of Energy (DOE) Water Power Program, the Instream Flow Project (IFP) was carried out by Oak Ridge National Laboratory (ORNL), Pacific Northwest National Laboratory (PNNL), and Argon National Laboratory (ANL) as an attempt to develop tools aimed at defining environmental flow needs for hydropower operations. The application of these tools ranges from national to site-specific scales; thus, the utility of each tool will depend on various phases of the environmental flow process. Given the complexity and sheer volume of applications used to determine environmentally acceptable flows for hydropower, a framework is needed to organize efforts into a staged process dependent upon spatial, temporal, and functional attributes. By far, the predominant domain for determining environmental flows related to hydropower is within the Federal Energy Regulatory Commission (FERC) relicensing process. This process can take multiple years and can be very expensive depending on the scale of each hydropower project. The utility of such a framework is that it can expedite the environmental flow process by 1) organizing data and applications to identify predictable relationships between flows and ecology, and 2) suggesting when and where tools should be used in the environmental flow process. In addition to regulatory procedures, a framework should also provide the coordination for a comprehensive research agenda to guide the science of environmental flows. This research program has further reaching benefits than just environmental flow determination by providing modeling applications, data, and geospatial layers to inform potential hydropower development. We address several objectives within this document that highlight the limitations of existing environmental flow paradigms and their applications to hydropower while presenting a new framework catered towards hydropower needs. Herein, we address the following objectives: 1) Provide a brief overview of the Natural Flow Regime paradigm and existing environmental flow frameworks that have been used to determine ecologically sensitive stream flows for hydropower operations. 2) Describe a new conceptual framework to aid in determining flows needed to meet ecological objectives with regard to hydropower operations. The framework is centralized around determining predictable relationships between flow and ecological responses. 3) Provide evidence of how efforts from ORNL, PNNL, and ANL have filled some of the gaps in this broader framework, and suggest how the framework can be used to set the stage for a research agenda for environmental flow.« less

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

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

Satchwell, Andrew; Cappers, Peter; Schwartz, Lisa

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

DISTILLER: a data integration framework to reveal condition dependency of complex regulons in Escherichia coli.

PubMed

Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen

2009-01-01

We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.

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

PubMed

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

2013-11-05

Regulatory science as a discipline has evolved over the past years with the object to boost and promote scientific rationale behind benefit/risk and decision making by regulatory authorities. The European Medicines Agency, EMA, the Food and Drug Administration, FDA, and the Japanese Pharmaceutical and Medical Devices Agency, PMDA, highlighted in their distinct ways the importance of regulatory science as a basis of good quality assessment in their strategic plans. The Medicines Evaluation Board, MEB, states: 'regulatory science is the science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making'. Through analysis of regulatory frameworks itself and their effectiveness, however, regulatory science can also advance knowledge of these systems in general. The comprehensive guidance that is issued to complete an application dossier for regulatory product approval has seldomly been scrutinized for its efficiency. Since it is the task of regulatory authorities to protect and promote public health, it is understood that they take a cautious approach in regulating drugs prior to market access. In general, the authorities are among the first to be blamed if dangerous or useless drugs were allowed to the market. Yet, building a regulatory framework that is not challenged continuously in terms of deliverables for public health and cost-effectiveness, might be counterproductive in the end. Regulatory science and research can help understand how and why regulatory decisions are made, and where renewed discussions may be warranted. The MEB supports regulatory science as an R&D activity to fuel primary regulatory processes on product evaluation and vigilance, but also invests in a 'looking into the mirror' approach. Along the line of the drug life-cycle, publicly available data are reviewed and their regulatory impact highlighted. If made explicit, regulatory research can open the door to evidence based regulatory practice and serve the regulator's contribution to innovative drug licensing today. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-Hazard Advanced Seismic Probabilistic Risk Assessment Tools and Applications

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

Coleman, Justin L.; Bolisetti, Chandu; Veeraraghavan, Swetha

Design of nuclear power plant (NPP) facilities to resist natural hazards has been a part of the regulatory process from the beginning of the NPP industry in the United States (US), but has evolved substantially over time. The original set of approaches and methods was entirely deterministic in nature and focused on a traditional engineering margins-based approach. However, over time probabilistic and risk-informed approaches were also developed and implemented in US Nuclear Regulatory Commission (NRC) guidance and regulation. A defense-in-depth framework has also been incorporated into US regulatory guidance over time. As a result, today, the US regulatory framework incorporatesmore » deterministic and probabilistic approaches for a range of different applications and for a range of natural hazard considerations. This framework will continue to evolve as a result of improved knowledge and newly identified regulatory needs and objectives, most notably in response to the NRC activities developed in response to the 2011 Fukushima accident in Japan. Although the US regulatory framework has continued to evolve over time, the tools, methods and data available to the US nuclear industry to meet the changing requirements have not kept pace. Notably, there is significant room for improvement in the tools and methods available for external event probabilistic risk assessment (PRA), which is the principal assessment approach used in risk-informed regulations and risk-informed decision-making applied to natural hazard assessment and design. This is particularly true if PRA is applied to natural hazards other than seismic loading. Development of a new set of tools and methods that incorporate current knowledge, modern best practice, and state-of-the-art computational resources would lead to more reliable assessment of facility risk and risk insights (e.g., the SSCs and accident sequences that are most risk-significant), with less uncertainty and reduced conservatisms.« less

Bringing New PET Drugs to Clinical Practice - A Regulatory Perspective

PubMed Central

Hung, Joseph C.

2013-01-01

The regulatory framework for radioactive drugs, in particular those used in positron emission tomography (PET) scans, has been gradually established since the release of the Food and Drug Administration Modernization Act in 1997. Various guidances specially tailored to accommodate special properties of PET drugs have been issued by the Food and Drug Administration (FDA) in order to ensure this valuable technology (i.e., PET molecular imaging) will continue to be available to patients and yet the safety and efficacy of PET drugs are well regulated so that public health will be protected. This article presents several key elements of this regulatory framework for PET drugs. New regulatory avenues proposed by the FDA to facilitate the research and development process to bring more new PET drugs to clinical practice, as well as to foster the opportunity of using “orphan” PET drugs in clinical practice are also discussed in this paper. PMID:24312157

75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... existing paragraph (b)(4) of the Rule, entitled ``Numerical Guidelines Applicable to Volatile Market Opens... existing paragraph (b)(2), which provides flexibility to FINRA to use different Numerical Guidelines or... of paragraph (b)(4) (``Numerical Guidelines Applicable to Volatile Market Opens'') of the existing...

[The Marketing of Healthcare Services in ENT-Clinics].

PubMed

Teschner, M; Lenarz, T

2016-07-01

The provision of healthcare services in Germany is based on fundamental principles of solidarity and is highly regulated. The question arises which conditions exist for marketing for healthcare services in ENT-clinics in Germany. The marketing options will be elicited using environmentally analytical considerations. The objectives can be achieved using measures derived from external instruments (service policy, pricing policy, distribution policy or communications policy) or from an internal instrument (human resources policy). The policy environment is particularly influenced by the regulatory framework, which particularly restricts the scope for both the pricing and communications policies. All measures must, however, reflect ethical frameworks, which are regarded as the fundamental premise underlying healthcare services and may be at odds with economic factors. Scope for flexibility in pricing exists only within the secondary healthcare market, and even there only to a limited extent. The significance of price in the marketing of healthcare services is thus very low. If marketing activities are to succeed, a market analysis must be carried out exploring the relevant factors for each individual provider. However, the essential precondition for the marketing of healthcare services is trust. The marketing of healthcare services differs from that of business management-oriented enterprises in other branches of economy. In the future the importance of marketing activities will increase. © Georg Thieme Verlag KG Stuttgart · New York.

Regulatory aspects of nanotechnology in the agri/feed/food sector in EU and non-EU countries.

PubMed

Amenta, Valeria; Aschberger, Karin; Arena, Maria; Bouwmeester, Hans; Botelho Moniz, Filipa; Brandhoff, Puck; Gottardo, Stefania; Marvin, Hans J P; Mech, Agnieszka; Quiros Pesudo, Laia; Rauscher, Hubert; Schoonjans, Reinhilde; Vettori, Maria Vittoria; Weigel, Stefan; Peters, Ruud J

2015-10-01

Nanotechnology has the potential to innovate the agricultural, feed and food sectors (hereinafter referred to as agri/feed/food). Applications that are marketed already include nano-encapsulated agrochemicals or nutrients, antimicrobial nanoparticles and active and intelligent food packaging. Many nano-enabled products are currently under research and development, and may enter the market in the near future. As for any other regulated product, applicants applying for market approval have to demonstrate the safe use of such new products without posing undue safety risks to the consumer and the environment. Several countries all over the world have been active in examining the appropriateness of their regulatory frameworks for dealing with nanotechnologies. As a consequence of this, different approaches have been taken in regulating nano-based products in agri/feed/food. The EU, along with Switzerland, were identified to be the only world region where nano-specific provisions have been incorporated in existing legislation, while in other regions nanomaterials are regulated more implicitly by mainly building on guidance for industry. This paper presents an overview and discusses the state of the art of different regulatory measures for nanomaterials in agri/feed/food, including legislation and guidance for safety assessment in EU and non-EU countries. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Time-dependent sorption of two novel fungicides in soils within a regulatory framework.

PubMed

Gulkowska, Anna; Buerge, Ignaz J; Poiger, Thomas; Kasteel, Roy

2016-12-01

Convincing experimental evidence suggests increased sorption of pesticides on soil over time, which, so far, has not been considered in the regulatory assessment of leaching to groundwater. Recently, Beulke and van Beinum (2012) proposed a guidance on how to conduct, analyse and use time-dependent sorption studies in pesticide registration. The applicability of the recommended experimental set-up and fitting procedure was examined for two fungicides, penflufen and fluxapyroxad, in four soils during a 170 day incubation experiment. The apparent distribution coefficient increased by a factor of 2.5-4.5 for penflufen and by a factor of 2.5-2.8 for fluxapyroxad. The recommended two-site, one-rate sorption model adequately described measurements of total mass and liquid phase concentration in the calcium chloride suspension and the calculated apparent distribution coefficient, passing all prescribed quality criteria for model fit and parameter reliability. The guidance is technically mature regarding the experimental set-up and parameterisation of the sorption model for the two moderately mobile and relatively persistent fungicides under investigation. These parameters can be used for transport modelling in soil, thereby recognising the existence of the experimentally observed, but in the regulatory leaching assessment of pesticides not yet routinely considered phenomenon of time-dependent sorption. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A semi-quantitative approach to GMO risk-benefit analysis.

PubMed

Morris, E Jane

2011-10-01

In many countries there are increasing calls for the benefits of genetically modified organisms (GMOs) to be considered as well as the risks, and for a risk-benefit analysis to form an integral part of GMO regulatory frameworks. This trend represents a shift away from the strict emphasis on risks, which is encapsulated in the Precautionary Principle that forms the basis for the Cartagena Protocol on Biosafety, and which is reflected in the national legislation of many countries. The introduction of risk-benefit analysis of GMOs would be facilitated if clear methodologies were available to support the analysis. Up to now, methodologies for risk-benefit analysis that would be applicable to the introduction of GMOs have not been well defined. This paper describes a relatively simple semi-quantitative methodology that could be easily applied as a decision support tool, giving particular consideration to the needs of regulators in developing countries where there are limited resources and experience. The application of the methodology is demonstrated using the release of an insect resistant maize variety in South Africa as a case study. The applicability of the method in the South African regulatory system is also discussed, as an example of what might be involved in introducing changes into an existing regulatory process.

Synchronous versus asynchronous modeling of gene regulatory networks.

PubMed

Garg, Abhishek; Di Cara, Alessandro; Xenarios, Ioannis; Mendoza, Luis; De Micheli, Giovanni

2008-09-01

In silico modeling of gene regulatory networks has gained some momentum recently due to increased interest in analyzing the dynamics of biological systems. This has been further facilitated by the increasing availability of experimental data on gene-gene, protein-protein and gene-protein interactions. The two dynamical properties that are often experimentally testable are perturbations and stable steady states. Although a lot of work has been done on the identification of steady states, not much work has been reported on in silico modeling of cellular differentiation processes. In this manuscript, we provide algorithms based on reduced ordered binary decision diagrams (ROBDDs) for Boolean modeling of gene regulatory networks. Algorithms for synchronous and asynchronous transition models have been proposed and their corresponding computational properties have been analyzed. These algorithms allow users to compute cyclic attractors of large networks that are currently not feasible using existing software. Hereby we provide a framework to analyze the effect of multiple gene perturbation protocols, and their effect on cell differentiation processes. These algorithms were validated on the T-helper model showing the correct steady state identification and Th1-Th2 cellular differentiation process. The software binaries for Windows and Linux platforms can be downloaded from http://si2.epfl.ch/~garg/genysis.html.

Neural processing of emotional-intensity predicts emotion regulation choice.

PubMed

Shafir, Roni; Thiruchselvam, Ravi; Suri, Gaurav; Gross, James J; Sheppes, Gal

2016-12-01

Emotional-intensity is a core characteristic of affective events that strongly determines how individuals choose to regulate their emotions. Our conceptual framework suggests that in high emotional-intensity situations, individuals prefer to disengage attention using distraction, which can more effectively block highly potent emotional information, as compared with engagement reappraisal, which is preferred in low emotional-intensity. However, existing supporting evidence remains indirect because prior intensity categorization of emotional stimuli was based on subjective measures that are potentially biased and only represent the endpoint of emotional-intensity processing. Accordingly, this study provides the first direct evidence for the role of online emotional-intensity processing in predicting behavioral regulatory-choices. Utilizing the high temporal resolution of event-related potentials, we evaluated online neural processing of stimuli's emotional-intensity (late positive potential, LPP) prior to regulatory-choices between distraction and reappraisal. Results showed that enhanced neural processing of intensity (enhanced LPP amplitudes) uniquely predicted (above subjective measures of intensity) increased tendency to subsequently choose distraction over reappraisal. Additionally, regulatory-choices led to adaptive consequences, demonstrated in finding that actual implementation of distraction relative to reappraisal-choice resulted in stronger attenuation of LPPs and self-reported arousal. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

IT Requirements Integration in High-Rise Construction Design Projects

NASA Astrophysics Data System (ADS)

Levina, Anastasia; Ilin, Igor; Esedulaev, Rustam

2018-03-01

The paper discusses the growing role of IT support for the operation of modern high-rise buildings, due to the complexity of managing engineering systems of buildings and the requirements of consumers for the IT infrastructure. The existing regulatory framework for the development of design documentation for construction, including high-rise buildings, is analyzed, and the lack of coherence in the development of this documentation with the requirements for the creation of an automated management system and the corresponding IT infrastructure is stated. The lack of integration between these areas is the cause of delays and inefficiencies both at the design stage and at the stage of putting the building into operation. The paper proposes an approach to coordinate the requirements of the IT infrastructure of high-rise buildings and design documentation for construction. The solution to this problem is possible within the framework of the enterprise architecture concept by coordinating the requirements of the IT and technological layers at the design stage of the construction.

Control of fluxes in metabolic networks.

PubMed

Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

2016-07-01

Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. © 2016 Basler et al.; Published by Cold Spring Harbor Laboratory Press.

Policy Considerations for Commercializing Natural Gas and Biomass CCUS

NASA Astrophysics Data System (ADS)

Abrahams, L.; Clavin, C.

2017-12-01

Captured CO2 from power generation has been discussed as an opportunity to improve the environmental sustainability of fossil fuel-based electricity generation and likely necessary technological solution necessary for meeting long-term climate change mitigation goals. In our presentation, we review the findings of a study of natural gas CCUS technology research and development and discuss their applications to biomass CCUS technology potential. Based on interviews conducted with key stakeholders in CCUS technology development and operations, this presentation will discuss these technical and economic challenges and potential policy opportunities to support commercial scale CCUS deployment. In current domestic and electricity and oil markets, CCUS faces economic challenges for commercial deployment. In particular, the economic viability of CCUS has been impacted by the sustained low oil prices that have limited the potential for enhanced oil recovery (EOR) to serve as a near-term utilization opportunity for the captured CO2. In addition, large scale commercial adoption of CCUS is constrained by regulatory inconsistencies and uncertainties across the United States, high initial capital costs, achieving familiarity with new technology applications to existing markets, developing a successful performance track record to acquire financing agreements, and competing against well-established incumbent technologies. CCUS also has additional technical hurdles for measurement, verification, and reporting within states that have existing policy and regulatory frameworks for climate change mitigation. In addition to fossil-fuel based CCUS, we will discuss emerging opportunities to utilize CCUS fueled by gasified biomass resulting in carbon negative power generation with expanded economic opportunities associated with the enhanced carbon sequestration. Successful technology development of CCUS technology requires a portfolio of research leading to technical advances, advances in financial instruments to leverage the benefits of multiple commodity markets (e.g. natural gas, oil, biomass), and policy instruments that address regulatory hurdles posed CCUS technology deployment.

DEVELOPMENT OF A FRAMEWORK FOR METALS RISK ASSESSMENT

EPA Science Inventory

Many EPA programs are faced with deciding whether and how to regulate toxic metals. These decisions range from setting regulatory standards for environmental releases, to establishing safe levels in different environmental media, to setting priorities for regulatory or voluntary...

30 CFR 761.16 - Submission and processing of requests for valid existing rights determinations.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Requirements for property rights demonstration. You must provide a property rights demonstration under... matter Regulatory authority Regulatory program 2 (d) Public roads Does not matter Regulatory authority Regulatory program 2 (e) Occupied dwellings Does not matter Regulatory authority Regulatory program 2 (f...

Department of Commerce Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... Clarify Amendment 13 and Subsequent Frameworks of 0648-AW95 the Northeast Multispecies Fishery Management... 0648-AY41 70 Framework 21 to the Atlantic Sea Scallop Fishery Management Plan 0648-AY43 71 Fishery...-Grouper Fishery Management Plan of the South Atlantic 0648-AX75 85 Framework Adjustment 44 and...

Boolean Dynamic Modeling Approaches to Study Plant Gene Regulatory Networks: Integration, Validation, and Prediction.

PubMed

Velderraín, José Dávila; Martínez-García, Juan Carlos; Álvarez-Buylla, Elena R

2017-01-01

Mathematical models based on dynamical systems theory are well-suited tools for the integration of available molecular experimental data into coherent frameworks in order to propose hypotheses about the cooperative regulatory mechanisms driving developmental processes. Computational analysis of the proposed models using well-established methods enables testing the hypotheses by contrasting predictions with observations. Within such framework, Boolean gene regulatory network dynamical models have been extensively used in modeling plant development. Boolean models are simple and intuitively appealing, ideal tools for collaborative efforts between theorists and experimentalists. In this chapter we present protocols used in our group for the study of diverse plant developmental processes. We focus on conceptual clarity and practical implementation, providing directions to the corresponding technical literature.

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

PubMed

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

2017-01-01

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

Advances in Atmospheric Radiation Measurements and Modeling Needed to Improve Air Safety

NASA Astrophysics Data System (ADS)

Tobiska, W. Kent; Atwell, William; Beck, Peter; Benton, Eric; Copeland, Kyle; Dyer, Clive; Gersey, Brad; Getley, Ian; Hands, Alex; Holland, Michael; Hong, Sunhak; Hwang, Junga; Jones, Bryn; Malone, Kathleen; Meier, Matthias M.; Mertens, Chris; Phillips, Tony; Ryden, Keith; Schwadron, Nathan; Wender, Stephen A.; Wilkins, Richard; Xapsos, Michael A.

2015-04-01

Air safety is tied to the phenomenon of ionizing radiation from space weather, primarily from galactic cosmic rays but also from solar energetic particles. A global framework for addressing radiation issues in this environment has been constructed, but more must be done at international and national levels. Health consequences from atmospheric radiation exposure are likely to exist. In addition, severe solar radiation events may cause economic consequences in the international aviation community due to exposure limits being reached by some crew members. Impacts from a radiation environment upon avionics from high-energy particles and low-energy, thermalized neutrons are now recognized as an area of active interest. A broad community recognizes that there are a number of mitigation paths that can be taken relative to the human tissue and avionics exposure risks. These include developing active monitoring and measurement programs as well as improving scientific modeling capabilities that can eventually be turned into operations. A number of roadblocks to risk mitigation still exist, such as effective pilot training programs as well as monitoring, measuring, and regulatory measures. An active international effort toward observing the weather of atmospheric radiation must occur to make progress in mitigating radiation exposure risks. Stakeholders in this process include standard-making bodies, scientific organizations, regulatory organizations, air traffic management systems, aircraft owners and operators, pilots and crew, and even the public.

Regulating Medicines in Croatia: Five-year Experience of Agency for Medicinal Products and Medical Devices

PubMed Central

Tomić, Siniša; Filipović Sučić, Anita; Plazonić, Ana; Truban Žulj, Rajka; Macolić Šarinić, Viola; Čudina, Branka; Ilić Martinac, Adrijana

2010-01-01

Aim To present the activities of the Agency for Medicinal Products and Medical Devices in the first 5 years of its existence and to define its future challenges. Methods Main activities within the scope of the Agency as a regulatory authority were retrospectively analyzed for the period from 2004-2008. Data were collected from the Agency’s database and analyzed by descriptive statistics. Results The number of issued medicine authorizations rose from 240 in 2004 to 580 in 2008. The greatest number of new chemical and biological entities was approved in 2005. The greatest number of regular quality controls (n = 5833) and special quality controls was performed in 2008 (n = 589), while the greatest number of off-shelf quality controls (n = 132) was performed in 2007. The greatest number of medicine labeling irregularities was found in 2007 (n = 19) and of quality irregularities in 2004 (n = 9). The greatest number of adverse reactions was reported in 2008 (n = 1393). The number of registered medical devices rose from 213 in 2004 to 565 in 2008. Conclusion Over its 5 years of existence, the Agency has successfully coped with the constant increase in workload. In the future, as Croatia enters the European Union, the Agency will have to face the challenge of joining the integrated European regulatory framework. PMID:20401952

Potential self-regulatory mechanisms of yoga for psychological health

PubMed Central

Gard, Tim; Noggle, Jessica J.; Park, Crystal L.; Vago, David R.; Wilson, Angela

2014-01-01

Research suggesting the beneficial effects of yoga on myriad aspects of psychological health has proliferated in recent years, yet there is currently no overarching framework by which to understand yoga’s potential beneficial effects. Here we provide a theoretical framework and systems-based network model of yoga that focuses on integration of top-down and bottom-up forms of self-regulation. We begin by contextualizing yoga in historical and contemporary settings, and then detail how specific components of yoga practice may affect cognitive, emotional, behavioral, and autonomic output under stress through an emphasis on interoception and bottom-up input, resulting in physical and psychological health. The model describes yoga practice as a comprehensive skillset of synergistic process tools that facilitate bidirectional feedback and integration between high- and low-level brain networks, and afferent and re-afferent input from interoceptive processes (somatosensory, viscerosensory, chemosensory). From a predictive coding perspective we propose a shift to perceptual inference for stress modulation and optimal self-regulation. We describe how the processes that sub-serve self-regulation become more automatized and efficient over time and practice, requiring less effort to initiate when necessary and terminate more rapidly when no longer needed. To support our proposed model, we present the available evidence for yoga affecting self-regulatory pathways, integrating existing constructs from behavior theory and cognitive neuroscience with emerging yoga and meditation research. This paper is intended to guide future basic and clinical research, specifically targeting areas of development in the treatment of stress-mediated psychological disorders. PMID:25368562

Reflections on the implementation of governance structures for early-stage clinical innovation.

PubMed

Cowie, Luke; Sandall, Jane; Ehrich, Kathryn

2013-12-01

This paper seeks to further explore the question of how best to monitor and govern innovative clinical procedures in their earliest phase of development. We examine the potential value of proposed governance frameworks, such as the IDEAL model, and examine the functioning of a novel procedures review committee. The paper draws upon 20 qualitative, semi-structured interviews. Nine interviews were conducted with members of a committee that was established as a means of governing innovative procedures within a large National Health Service Foundation Trust hospital in the UK. Eleven interviews were conducted with health providers involved with the development of a variety of novel clinical procedures. Prominent themes from the data include the potential willingness of clinicians to engage with regulatory frameworks for innovative procedures, existing ways in which clinicians and others attempt to ensure patient's safety and manage uncertainty in the context of novel procedures, views on the potential benefits and drawbacks of engaging with a review committee for novel procedures, and the pragmatic considerations and potential unintended consequences that are entailed in the implementation of regulatory requirements for the monitoring of innovative procedures. The views of committee members and clinical innovators help us to understand the practical issues of implementing governance structures for novel clinical procedures. The data illustrate those factors that must be taken into account if governance is to support innovation rather than act as an inhibiting factor in the development of new clinical procedures. © 2012 John Wiley & Sons Ltd.

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

PubMed

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

2018-05-18

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

DISTILLER: a data integration framework to reveal condition dependency of complex regulons in Escherichia coli

PubMed Central

Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen

2009-01-01

We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity. PMID:19265557

Researchers', Regulators', and Sponsors' Views on Pediatric Clinical Trials: A Multinational Study.

PubMed

Joseph, Pathma D; Craig, Jonathan C; Tong, Allison; Caldwell, Patrina H Y

2016-10-01

The last decade has seen dramatic changes in the regulatory landscape to support more trials involving children, but child-specific challenges and inequitable conduct across income regions persist. The goal of this study was to describe the attitudes and opinions of stakeholders toward trials in children, to inform additional strategies to promote more high-quality, relevant pediatric trials across the globe. Key informant semi-structured interviews were conducted with stakeholders (researchers, regulators, and sponsors) who were purposively sampled from low- to middle-income countries and high-income countries. The transcripts were thematically analyzed. Thirty-five stakeholders from 10 countries were interviewed. Five major themes were identified: addressing pervasive inequities (paucity of safety and efficacy data, knowledge disparities, volatile environment, double standards, contextual relevance, market-driven forces, industry sponsorship bias and prohibitive costs); contending with infrastructural barriers (resource constraints, dearth of pediatric trial expertise, and logistical complexities); navigating complex ethical and regulatory frameworks ("draconian" oversight, ambiguous requirements, exploitation, excessive paternalism and precariousness of coercion versus volunteerism); respecting uniqueness of children (pediatric research paradigms, child-appropriate approaches, and family-centered empowerment); and driving evidence-based child health (advocacy, opportunities, treatment access, best practices, and research prioritization). Stakeholders acknowledge that changes in the regulatory environment have encouraged more trials in children, but they contend that inequities and political, regulatory, and resource barriers continue to exist. Embedding trials as part of routine clinical care, addressing the unique needs of children, and streamlining regulatory approvals were suggested. Stakeholders recommended increasing international collaboration, establishing centralized trials infrastructure, and aligning research to child health priorities to encourage trials that address global child health care needs. Copyright © 2016 by the American Academy of Pediatrics.

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

PubMed

Byrom, Bill; Watson, Chris; Doll, Helen; Coons, Stephen Joel; Eremenco, Sonya; Ballinger, Rachel; Mc Carthy, Marie; Crescioni, Mabel; O'Donohoe, Paul; Howry, Cindy

2018-06-01

Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

75 FR 79049 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

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

Review of PSR framework and development of a DPSIR model to assess greenhouse effect in Taiwan.

PubMed

Huang, Hui-Fen; Kuo, Jeff; Lo, Shang-Lien

2011-06-01

In dealing with the complex issues of greenhouse gas (GHG) emission and climate change mitigation, many interrelated factors such as cost, level of technology development, supply and demand of energy, structure of industry, and expenditures on research and development exist. Using indicators to monitor environmental impacts and evaluate the efficacies of policies and regulations has been practiced for a long time, and it can serve as a useful tool for decision making and for comparison between different countries. Although numerous indicators have been developed for relevant subjects, integrated approaches that consider individual changes, dynamic interaction, and multi-dimensions of indicators are scarce. This paper aimed to develop a Driving Force-Pressure-State-Impact-Response (DPSIR) framework to assess the problems. This DPSIR model is mainly related to energy consumption, environmental impacts, and policy responses. The objectives of the paper were: (1) conduct a literature review on the indicators that have been used in GHG-related studies; (2) develop a DPSIR model that incorporates GHG-related indicators and evaluate their relationships using a cause-effect chain of GHG emission; and (3) develop a calculative method that can be used to explain the dynamic correlation among the interdependent indicators. Taiwan is a significant source of global GHG emissions. A case study, using the developed framework and Taiwan's actual data of the past two decades, was conducted. The results indicate that regulatory strategies for pollution control are inadequate in terms of ensuring environmental quality, and the nature does not have the capability to revert the impacts from the existing level of pollution.

Building a Conceptual Framework to Study the Effect of HIV Stigma-Reduction Intervention Strategies on HIV Test Uptake: A Scoping Review.

PubMed

Thapa, Subash; Hannes, Karin; Cargo, Margaret; Buve, Anne; Aro, Arja R; Mathei, Catharina

A scoping review of grey and peer-reviewed literature was conducted to develop a conceptual framework to illustrate mechanisms involved in reducing HIV stigma and increasing HIV test uptake. We followed a three-step approach to exploring the literature: developing concepts, organizing and categorizing concepts, and synthesizing concepts into a framework. The framework contains four types of intervention strategies: awareness creation, influencing normative behavior, providing support, and developing regulatory laws. The awareness creation strategy generally improves knowledge and the influencing normative behavior strategy changes stigmatizing attitudes and behaviors, and subsequently, increases HIV test uptake. Providing support and development of regulatory law strategies changes actual stigmatizing behaviors of the people, and subsequently, increases HIV test uptake. The framework further outlines that the mechanisms described are influenced by the interaction of various social-contextual and individual factors. The framework sheds new light on the effects of HIV stigma-reduction intervention strategies and HIV test uptake. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

A strategy for regulatory action when new adverse effects of a licensed product emerge.

PubMed

Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

2009-01-01

Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

Strengthening the Canadian alcohol advertising regulatory system.

PubMed

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

2012-05-24

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

Transgenic proteins in agricultural biotechnology: The toxicology forum 40th annual summer meeting.

PubMed

Sherman, James H; Choudhuri, Supratim; Vicini, John L

2015-12-01

During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The range of current commercial crops and commercial crop traits related to transgenic proteins were reviewed and example crop traits discussed, including insecticidal resistance conferred by Bt proteins and the development of nutritionally enhanced food such as Golden Rice. The existing regulatory framework in the USA, with an emphasis on US FDA's role in evaluating the safety of genetically engineered crops under the regulatory umbrella of the FD&C Act was reviewed. Consideration was given to the polarized politics surrounding agricultural biotechnology, the rise of open access journals, and the influence of the internet and social media in shaping public opinion. Numerous questions related to misconceptions regarding current products and regulations were discussed, highlighting the need for more scientists to take an active role in public discourse to facilitate public acceptance and adoption of new technologies and to enable science-based regulations. Copyright © 2015 Elsevier Inc. All rights reserved.

Making message recipients "feel right": how nonverbal cues can increase persuasion.

PubMed

Cesario, Joseph; Higgins, E Tory

2008-05-01

Nonverbal cues are an inherent component of most persuasive appeals. We use regulatory-fit theory as a framework for understanding the effect of nonverbal cues on a message's effectiveness, and as a foundation for developing a new persuasion technique. We propose that when the nonverbal cues of a message source sustain the motivational orientation of the recipient, the recipient experiences regulatory fit and feels right, and that this experience influences the message's effectiveness. Experimental results support these predictions. Participants experiencing regulatory fit (promotion-focus participants viewing messages delivered in an eager nonverbal style, prevention-focus participants viewing messages delivered in a vigilant nonverbal style) had more positive attitudes toward a message's topic and greater intentions to behave in accordance with its recommendation than did participants experiencing nonfit. Feeling right was also greater for participants experiencing fit than for those experiencing nonfit and was associated with greater message effectiveness. Regulatory-fit theory provides a framework for making precise predictions about when and for whom a nonverbal cue will affect persuasion.

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

PubMed

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

2017-03-15

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

Advancing the adverse outcome pathway framework and its ...

EPA Pesticide Factsheets

Regulatory agencies worldwide are confronted with the challenging task of assessing the risks of thousands of chemicals to protect both human health and the environment. Traditional toxicity testing largely relies on apical endpoints from whole animal studies, which, in addition to ethical concerns, is costly and time prohibitive. As a result, the utility of mechanism-based in silico, in vitro, and in vivo approaches to support chemical safety evaluations have increasingly been explored. An approach that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP) framework. A number of international workshops and expert meetings have been held over the past years focusing on the AOP framework and its applications to chemical risk assessment. Although, these interactions have illustrated the necessity of expert guidance in moving the science of AOPs and their applications forward, there is also the recognition that a broader survey of the scientific community could be useful in guiding future initiatives in the AOP arena. To that end, a Horizon Scanning exercise was conducted to solicit questions from the global scientific community concerning the challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision making. Over a 4 month ques

Harnessing Diversity towards the Reconstructing of Large Scale Gene Regulatory Networks

PubMed Central

Yamanaka, Ryota; Kitano, Hiroaki

2013-01-01

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. PMID:24278007

Intrinsic limits to gene regulation by global crosstalk

NASA Astrophysics Data System (ADS)

Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

Toward a Regulatory Framework for the Waterpipe.

PubMed

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

2016-10-01

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

Toward a Regulatory Framework for the Waterpipe

PubMed Central

Salloum, Ramzi G.; Asfar, Taghrid

2016-01-01

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

Protecting the public or setting the bar too high? Understanding the causes and consequences of regulatory actions of front-line regulators and specialized drug shop operators in Kenya.

PubMed

Wafula, Francis; Molyneux, Catherine; Mackintosh, Maureen; Goodman, Catherine

2013-11-01

The problem of poor regulatory compliance has been widely reported across private health providers in developing countries. Less known are the underlying reasons for poor compliance, especially with regards to the roles played by front-line regulatory staff, and the regulatory institution as a whole. We designed a qualitative study to address this gap, with the study questions and tools drawing on a conceptual framework informed by theoretical literature on regulation. Data were collected from specialized drug shops (SDSs) in two rural districts in Western Kenya in 2011 through eight focus group discussions, and from regulatory staff from organizations governing the pharmaceutical sector through a total of 24 in-depth interviews. We found that relationships between front-line regulators and SDS operators were a strong influence on regulatory behaviour, often resulting in non-compliance and perverse outcomes such as corruption. It emerged that separate regulatory streams operated in urban and rural locations, based mainly on differing relationships between the front-line regulators and SDS operators, and on broader factors such as the competition environment and community expectations. Effective incentive structures for regulatory staff were either absent, or poorly linked to performance in regulatory organizations, resulting in divergences between the purposes of the regulatory organization and activities of front-line staff. Given the rural-urban differences in the practice environment, the introduction of lower retail practice requirements for rural SDSs could be considered. This would allow illegally operated shops to be brought within the regulatory framework, facilitating good quality provision of essential commodities to marginalized areas, without lowering the practice requirements for the better complying urban SDSs. In addition, regulatory organizations need to devise incentives that better link the level of effort to rewards such as professional advancement of regulatory staff. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protecting the public or setting the bar too high? Understanding the causes and consequences of regulatory actions of front-line regulators and specialized drug shop operators in Kenya

PubMed Central

Wafula, Francis; Molyneux, Catherine; Mackintosh, Maureen; Goodman, Catherine

2013-01-01

The problem of poor regulatory compliance has been widely reported across private health providers in developing countries. Less known are the underlying reasons for poor compliance, especially with regards to the roles played by front-line regulatory staff, and the regulatory institution as a whole. We designed a qualitative study to address this gap, with the study questions and tools drawing on a conceptual framework informed by theoretical literature on regulation. Data were collected from specialized drug shops (SDSs) in two rural districts in Western Kenya in 2011 through eight focus group discussions, and from regulatory staff from organizations governing the pharmaceutical sector through a total of 24 in-depth interviews. We found that relationships between front-line regulators and SDS operators were a strong influence on regulatory behaviour, often resulting in non-compliance and perverse outcomes such as corruption. It emerged that separate regulatory streams operated in urban and rural locations, based mainly on differing relationships between the front-line regulators and SDS operators, and on broader factors such as the competition environment and community expectations. Effective incentive structures for regulatory staff were either absent, or poorly linked to performance in regulatory organizations, resulting in divergences between the purposes of the regulatory organization and activities of front-line staff. Given the rural-urban differences in the practice environment, the introduction of lower retail practice requirements for rural SDSs could be considered. This would allow illegally operated shops to be brought within the regulatory framework, facilitating good quality provision of essential commodities to marginalized areas, without lowering the practice requirements for the better complying urban SDSs. In addition, regulatory organizations need to devise incentives that better link the level of effort to rewards such as professional advancement of regulatory staff. PMID:24016728

A fair share for the orphans: ethical guidelines for a fair distribution of resources within the bounds of the 10-year-old European Orphan Drug Regulation.

PubMed

Pinxten, Wim; Denier, Yvonne; Dooms, Marc; Cassiman, Jean-Jacques; Dierickx, Kris

2012-03-01

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and leave unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases.

Limiting the consumption of sugar sweetened beverages in Mexico's obesogenic environment: a qualitative policy review and stakeholder analysis.

PubMed

Moise, Nathalie; Cifuentes, Enrique; Orozco, Emanuel; Willett, Walter

2011-11-01

Mexico is building a legal framework to address its childhood obesity epidemic. Sugar sweetened beverages (SSB) in the school environment represent a major policy challenge. We addressed the following questions: What barriers inhibit political attention to SSB and childhood obesity? What political instruments, international and national, exist to guide agenda setting in Mexico? What opportunities exist for policy adoption? We conducted a systematic review of international and national legal instruments concerned with SSB consumption. We traced process, conducting interviews with key informants. Thematic analysis helped us identify barriers and opportunities for public health interventions. We found 11 national policy instruments, but detected implementation gaps and weak fiscal policies on SSB consumption in schools: limited drinking water infrastructure, SSB industry interests, and regulatory ambiguities addressing reduction of sugar in beverages. Public policy should target marketing practices and taxation. The school environment remains a promising target for policy. Access to safe drinking water must complement comprehensive and multi-sector policy approaches to reduce access to SSB.

78 FR 909 - Further Proposed Guidance Regarding Compliance With Certain Swap Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... establish a new regulatory framework for swaps. The legislation was enacted to reduce systemic risk... increase understanding of each other's regulatory approaches and to harmonize the cross-border approaches... may lead to divergent approaches to cross-border activities. The Commission also recognizes the...

Regression Analysis of Combined Gene Expression Regulation in Acute Myeloid Leukemia

PubMed Central

Li, Yue; Liang, Minggao; Zhang, Zhaolei

2014-01-01

Gene expression is a combinatorial function of genetic/epigenetic factors such as copy number variation (CNV), DNA methylation (DM), transcription factors (TF) occupancy, and microRNA (miRNA) post-transcriptional regulation. At the maturity of microarray/sequencing technologies, large amounts of data measuring the genome-wide signals of those factors became available from Encyclopedia of DNA Elements (ENCODE) and The Cancer Genome Atlas (TCGA). However, there is a lack of an integrative model to take full advantage of these rich yet heterogeneous data. To this end, we developed RACER (Regression Analysis of Combined Expression Regulation), which fits the mRNA expression as response using as explanatory variables, the TF data from ENCODE, and CNV, DM, miRNA expression signals from TCGA. Briefly, RACER first infers the sample-specific regulatory activities by TFs and miRNAs, which are then used as inputs to infer specific TF/miRNA-gene interactions. Such a two-stage regression framework circumvents a common difficulty in integrating ENCODE data measured in generic cell-line with the sample-specific TCGA measurements. As a case study, we integrated Acute Myeloid Leukemia (AML) data from TCGA and the related TF binding data measured in K562 from ENCODE. As a proof-of-concept, we first verified our model formalism by 10-fold cross-validation on predicting gene expression. We next evaluated RACER on recovering known regulatory interactions, and demonstrated its superior statistical power over existing methods in detecting known miRNA/TF targets. Additionally, we developed a feature selection procedure, which identified 18 regulators, whose activities clustered consistently with cytogenetic risk groups. One of the selected regulators is miR-548p, whose inferred targets were significantly enriched for leukemia-related pathway, implicating its novel role in AML pathogenesis. Moreover, survival analysis using the inferred activities identified C-Fos as a potential AML prognostic marker. Together, we provided a novel framework that successfully integrated the TCGA and ENCODE data in revealing AML-specific regulatory program at global level. PMID:25340776

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework.

PubMed

Cozzi, Emanuele; Tallacchini, Mariachiara; Flanagan, Enda B; Pierson, Richard N; Sykes, Megan; Vanderpool, Harold Y

2009-01-01

The outstanding results recently obtained in islet xenotransplantation suggest that porcine islet clinical trials may soon be scientifically appropriate. Before the initiation of such clinical studies, however, it is essential that a series of key ethical and regulatory conditions are satisfied. As far as ethics is concerned, the fundamental requirements have been previously reported in a position paper of the Ethics Committee of the International Xenotransplantation Association. These include aspects related to the selection of adequately informed, appropriate recipients; animal breeding and welfare; safety issues and the need for a favorable risk/benefit assessment based on strong efficacy data in relevant xenotransplantation studies in the primate. As most diabetic patients are not at risk of short-term mortality without islet transplantation, only a small subset of patients could currently be considered for any type of islet transplant. However, there are potential advantages to xenotransplantation that could result in a favorable benefit-over-harm determination for islet xenotransplantation in this subpopulation and ultimately in a broader population of diabetic patients. With regard to regulatory aspects, the key concepts underlying the development of the regulatory models in existence in the United States, Europe and New Zealand are discussed. Each of these models provides an example of a well-defined regulatory approach to ensure the initiation of well-regulated and ethically acceptable clinical islet xenotransplantation trials. At this stage, it becomes apparent that only a well-coordinated international effort such as that initiated by the World Health Organization, aimed at harmonizing xenotransplantation procedures according to the highest ethical and regulatory standards on a global scale, will enable the initiation of clinical xenotransplantation trials under the best auspices for its success and minimize any risk of failure.

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

PubMed Central

Georgopoulos, P G

1995-01-01

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

The impact of council directive 2011/70/EURATOM and IAEA joint convention review meetings on the ongoing establishment of the Portuguese regulatory framework and on the future of national radioactive waste

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

Paiva, Isabel; Trindade, Romao B.

Council Directive 2011/70/EURATOM of 19 July 2011, establishing a Community framework for the responsible and safe management of spent fuel and radioactive waste will enter in force August 2013 in all EU Member States. Portugal has already started preparing its legislative framework to accommodate the new legislative piece. However, the first report of Portugal to the Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management of the IAEA, in Vienna, 2012, has shown that Portugal still has many steps to overcome to establish a successful and effective basic regulatory framework. The existencemore » of many competent authorities related to the radiological protection area and a newly independent commission that is still looking on how to fulfill its regulator role in other areas such as the radioactive waste management makes quite challenging the full application of the new directive as well as compliance that Portugal will have to show in the next Joint Convention review meeting in order to meet the obligations of the Convention. In this paper, the reality of the regulatory Portuguese framework on radiological protection, nuclear safety and radioactive waste management is presented. Discussion of the future impact of the new legislation and its consequences such as the need to setup the national program on radioactive waste management is critical discussed. (authors)« less

Function, dynamics and evolution of network motif modules in integrated gene regulatory networks of worm and plant.

PubMed

Defoort, Jonas; Van de Peer, Yves; Vermeirssen, Vanessa

2018-06-05

Gene regulatory networks (GRNs) consist of different molecular interactions that closely work together to establish proper gene expression in time and space. Especially in higher eukaryotes, many questions remain on how these interactions collectively coordinate gene regulation. We study high quality GRNs consisting of undirected protein-protein, genetic and homologous interactions, and directed protein-DNA, regulatory and miRNA-mRNA interactions in the worm Caenorhabditis elegans and the plant Arabidopsis thaliana. Our data-integration framework integrates interactions in composite network motifs, clusters these in biologically relevant, higher-order topological network motif modules, overlays these with gene expression profiles and discovers novel connections between modules and regulators. Similar modules exist in the integrated GRNs of worm and plant. We show how experimental or computational methodologies underlying a certain data type impact network topology. Through phylogenetic decomposition, we found that proteins of worm and plant tend to functionally interact with proteins of a similar age, while at the regulatory level TFs favor same age, but also older target genes. Despite some influence of the duplication mode difference, we also observe at the motif and module level for both species a preference for age homogeneity for undirected and age heterogeneity for directed interactions. This leads to a model where novel genes are added together to the GRNs in a specific biological functional context, regulated by one or more TFs that also target older genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that are potentially universal in all species.

Verification and Validation Strategy for LWRS Tools

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

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

2012-09-01

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

A Framework for the Evaluation of Biosecurity, Commercial, Regulatory, and Scientific Impacts of Plant Viruses and Viroids Identified by NGS Technologies

PubMed Central

Massart, Sebastien; Candresse, Thierry; Gil, José; Lacomme, Christophe; Predajna, Lukas; Ravnikar, Maja; Reynard, Jean-Sébastien; Rumbou, Artemis; Saldarelli, Pasquale; Škorić, Dijana; Vainio, Eeva J.; Valkonen, Jari P. T.; Vanderschuren, Hervé; Varveri, Christina; Wetzel, Thierry

2017-01-01

Recent advances in high-throughput sequencing technologies and bioinformatics have generated huge new opportunities for discovering and diagnosing plant viruses and viroids. Plant virology has undoubtedly benefited from these new methodologies, but at the same time, faces now substantial bottlenecks, namely the biological characterization of the newly discovered viruses and the analysis of their impact at the biosecurity, commercial, regulatory, and scientific levels. This paper proposes a scaled and progressive scientific framework for efficient biological characterization and risk assessment when a previously known or a new plant virus is detected by next generation sequencing (NGS) technologies. Four case studies are also presented to illustrate the need for such a framework, and to discuss the scenarios. PMID:28174561

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

PubMed Central

Liu, Zhi-Ping

2015-01-01

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

Reverse engineering of logic-based differential equation models using a mixed-integer dynamic optimization approach

PubMed Central

Henriques, David; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R.

2015-01-01

Motivation: Systems biology models can be used to test new hypotheses formulated on the basis of previous knowledge or new experimental data, contradictory with a previously existing model. New hypotheses often come in the shape of a set of possible regulatory mechanisms. This search is usually not limited to finding a single regulation link, but rather a combination of links subject to great uncertainty or no information about the kinetic parameters. Results: In this work, we combine a logic-based formalism, to describe all the possible regulatory structures for a given dynamic model of a pathway, with mixed-integer dynamic optimization (MIDO). This framework aims to simultaneously identify the regulatory structure (represented by binary parameters) and the real-valued parameters that are consistent with the available experimental data, resulting in a logic-based differential equation model. The alternative to this would be to perform real-valued parameter estimation for each possible model structure, which is not tractable for models of the size presented in this work. The performance of the method presented here is illustrated with several case studies: a synthetic pathway problem of signaling regulation, a two-component signal transduction pathway in bacterial homeostasis, and a signaling network in liver cancer cells. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: julio@iim.csic.es or saezrodriguez@ebi.ac.uk PMID:26002881

Reverse engineering of logic-based differential equation models using a mixed-integer dynamic optimization approach.

PubMed

Henriques, David; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R

2015-09-15

Systems biology models can be used to test new hypotheses formulated on the basis of previous knowledge or new experimental data, contradictory with a previously existing model. New hypotheses often come in the shape of a set of possible regulatory mechanisms. This search is usually not limited to finding a single regulation link, but rather a combination of links subject to great uncertainty or no information about the kinetic parameters. In this work, we combine a logic-based formalism, to describe all the possible regulatory structures for a given dynamic model of a pathway, with mixed-integer dynamic optimization (MIDO). This framework aims to simultaneously identify the regulatory structure (represented by binary parameters) and the real-valued parameters that are consistent with the available experimental data, resulting in a logic-based differential equation model. The alternative to this would be to perform real-valued parameter estimation for each possible model structure, which is not tractable for models of the size presented in this work. The performance of the method presented here is illustrated with several case studies: a synthetic pathway problem of signaling regulation, a two-component signal transduction pathway in bacterial homeostasis, and a signaling network in liver cancer cells. Supplementary data are available at Bioinformatics online. julio@iim.csic.es or saezrodriguez@ebi.ac.uk. © The Author 2015. Published by Oxford University Press.

Incentive regulation and performance measurement of the Portuguese solid waste management services.

PubMed

Marques, Rui Cunha; Simões, Pedro

2009-03-01

Measuring the performance of solid waste management services usually uncovers very high potential for gains in efficiency and productivity. This circumstance occurs, naturally, due to the fact that these services are outside the market and because they are subjected to various market failures in their organizational framework. The aim of this study was to examine the Portuguese regulatory model and to measure the performance of the Portuguese solid waste management services in order to identify the major reforms carried out and their outcomes. As a first objective, the sunshine regulatory approach adopted in Portugal, in which performance comparison and its public discussion are the main tools, was investigated. The second objective was to compute the efficiency of the Portuguese solid waste management services by means of the non-parametric technique of data envelopment analysis (DEA), evaluating the Portuguese regulatory model and the existing market structure, as well as the influence of the operational environment on efficiency. The benchmarking frontier technique of DEA is particularly useful in the efficiency measurement of public utilities, in which knowledge of the production function is relatively scarce. Several DEA models were used and they all depicted significant inefficiency. The study also proved that efficiency did not depend on ownership (public or private) and that there was no difference in efficiency between the players, irrespective of whether they were regulated or not.

Practices and ethical concerns regarding preimplantation diagnosis. Who regulates preimplantation genetic diagnosis in Brazil?

PubMed Central

Damian, B.B.; Bonetti, T.C.S.; Horovitz, D.D.G.

2014-01-01

Preimplantation genetic diagnosis (PGD) was originally developed to diagnose embryo-related genetic abnormalities for couples who present a high risk of a specific inherited disorder. Because this technology involves embryo selection, the medical, bioethical, and legal implications of the technique have been debated, particularly when it is used to select features that are not related to serious diseases. Although several initiatives have attempted to achieve regulatory harmonization, the diversity of healthcare services available and the presence of cultural differences have hampered attempts to achieve this goal. Thus, in different countries, the provision of PGD and regulatory frameworks reflect the perceptions of scientific groups, legislators, and society regarding this technology. In Brazil, several texts have been analyzed by the National Congress to regulate the use of assisted reproduction technologies. Legislative debates, however, are not conclusive, and limited information has been published on how PGD is specifically regulated. The country requires the development of new regulatory standards to ensure adequate access to this technology and to guarantee its safe practice. This study examined official documents published on PGD regulation in Brazil and demonstrated how little direct oversight of PGD currently exists. It provides relevant information to encourage reflection on a particular regulation model in a Brazilian context, and should serve as part of the basis to enable further reform of the clinical practice of PGD in the country. PMID:25493379

76 FR 59066 - Notice of Regulatory Review Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... [No. 2011-N-10] Notice of Regulatory Review Plan AGENCY: Federal Housing Finance Agency. ACTION... of and requesting comments on the FHFA interim regulatory review plan for review of existing... comments on all aspects of the interim regulatory review plan, including legal and policy considerations...

75 FR 43207 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to an existing.... Jervey, Acting Chief, Regulatory Guide Development Branch, Division of Engineering, Office of Nuclear...

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

PubMed

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

2013-12-01

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

The Tasman Spirit oil spill: implications for regulatory change in Pakistan.

PubMed

Mian, Saima; Bennett, Suzan

2009-07-01

An oil spill in July 2003 from the tanker Tasman Spirit attracted considerable public and media attention in Pakistan. This paper focuses on the experience of a developing country such as Pakistan in dealing with a major oil spill and its impact on bringing about change in the national regulatory framework. A major outcome has been the ratification of the International Convention on Civil Liability for Oil Pollution Damage 1992, which came into force in March 2006 in Pakistan. The convention provides a compensation mechanism for victims incurring oil pollution damages from maritime casualties involving oil laden ships. Several additional changes are still required to improve the country's ability to cope with marine oil spills. These include the development of a comprehensive domestic regulatory framework, implementation of an effective contingency plan, and capacity building of all relevant agencies.

Weight of evidence evaluation of adverse outcome pathways converging at impaired vitellogenin synthesis leading to reproductive impairment

EPA Science Inventory

Adverse outcome pathways (AOPs) provide a framework that supports greater use of mechanistic data measured at lower levels of biological organization as a basis for regulatory decision-making. However, it is recognized that different types of regulatory applications and decisions...

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

PubMed

Harvey, B E; Alpert, S

1997-01-01

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

Opportunities for animal alternatives implementation in the evolving OECD fish testing framework

EPA Science Inventory

This presentation reviews opportunities for animal alternative approaches in the FTF. These will be placed in the context of in vivo tests required in many regulatory situations for the registration of industrial chemicals, pharmaceuticals, and agrochemicals. The Framework inte...

Disrupting incrementalism in health care innovation.

PubMed

Soleimani, Farzad; Zenios, Stefanos

2011-08-01

To build enabling innovation frameworks for health care entrepreneurs to better identify, evaluate, and pursue entrepreneurial opportunities. Powerful frameworks have been developed to enable entrepreneurs and investors identify which opportunity areas are worth pursuing and which start-up ideas have the potential to succeed. These frameworks, however, have not been clearly defined and interpreted for innovations in health care. Having a better understanding of the process of innovation in health care allows physician entrepreneurs to innovate more successfully. A review of academic literature was conducted. Concepts and frameworks related to technology innovation were analyzed. A new set of health care specific frameworks was developed. These frameworks were then applied to innovations in various health care subsectors. Health care entrepreneurs would greatly benefit from distinguishing between incremental and disruptive innovations. The US regulatory and reimbursement systems favor incrementalism with a greater chance of success for established players. Small companies and individual groups, however, are more likely to thrive if they adopt a disruptive strategy. Disruption in health care occurs through various mechanisms as detailed in this article. While the main mechanism of disruption might vary across different health care subsectors, it is shown that disruptive innovations consistently require a component of contrarian interpretation to guarantee considerable payoff. If health care entrepreneurs choose to adopt an incrementalist approach, they need to build the risk of disruption into their models and also ascertain that they have a very strong intellectual property (IP) position to weather competition from established players. On the contrary, if they choose to pursue disruption in the market, albeit the competition will be less severe, they need to recognize that the regulatory and reimbursement hurdles are going to be very high. Thus, they would benefit from seeking market opportunities that are large enough to warrant greater regulatory and reimbursement risks.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

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

Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

PubMed

Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

2016-05-01

Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

Development of physiotherapy inherent requirement statements - an Australian experience.

PubMed

Bialocerkowski, Andrea; Johnson, Amanda; Allan, Trevor; Phillips, Kirrilee

2013-04-16

The United Nations Convention on the Rights of People with Disabilities promotes equal rights of people with a disability in all aspects of their life including their education. In Australia, Disability Discrimination legislation underpins this Convention. It mandates that higher education providers must demonstrate that no discrimination has occurred and all reasonable accommodations have been considered and implemented, to facilitate access and inclusion for a student with a disability. The first step to meeting legislative requirements is to provide students with information on the inherent requirements of a course. This paper describes the steps which were taken to develop inherent requirement statements for a 4-year entry-level physiotherapy program at one Australian university. Inherent requirement statements were developed using an existing framework, which was endorsed and mandated by the University. Items which described inherencies were extracted from Australian physiotherapy professional standards and statutory regulatory requirements, and units contained in the physiotherapy program. Data were integrated into the 8 prescribed domains: ethical behaviour, behavioural stability, legal, communication, cognition, sensory abilities, strength and mobility, and sustainable performance. Statements for each domain were developed using a 5-level framework (introductory statement, description of the inherent requirement, justification for inherency, characteristics of reasonable adjustments and exemplars) and reviewed by a University Review Panel. Refinement of statements continued until no further changes were required. Fifteen physiotherapy inherent requirement statements were developed. The eight domains identified in the existing framework, developed for Nursing, were relevant to the study of physiotherapy. The inherent requirement statements developed in this study provide a transparent, defensible position on the current requirements of physiotherapy study at one Australian university. These statements are transferable to other physiotherapy programs in Australia due to standardised physiotherapy accreditation requirements. The model and framework could be applied to other health professional courses and used to explore the physiotherapy inherent requirements from an international perspective.

Risk and resilience in the shale gas context: a nexus perspective

NASA Astrophysics Data System (ADS)

Rosales, T. Y.; Notte, C. A.; Allen, D. M.; Kirste, D. M.

2014-12-01

The accelerated exploration for and development of unconventional gas plays around the world has raised public concern about potential risks to human health and the environment. In this study, a risk assessment framework specific to shale gas development is proposed. The framework aims to quantify and/or qualify both risk and resilience within a water-energy nexus context, using a comprehensive approach that considers environment, health and policy. The risk assessment framework is intended to be flexible so that it can be used in different regions, but will be tested in North East British Columbia, Canada where shale gas development is rapidly expanding. The main components of risk include hazards, susceptibility and potential consequences, which will be evaluated in space and time using ArcGIS software. The hazards are associated with all phases of shale gas development and include: water, air, and soil contamination; water use (surface and groundwater), and land use disturbance, and their assessment will take into account where they may occur, their frequency, duration and magnitude. Hazard-specific susceptibility maps will be generated based on the physical characteristics of the environment (e.g. soil, geology, hydrology, topography) as well as water source information (e.g. well locations), community footprints, etc. When combined with an evaluation of potential consequences, the resulting set of spatial risk maps can then be used for water resource management, land use planning, and industry permitting. Resilience, which buffers risk, here considers the existing regulatory framework and whether or not existing regulations can mitigate risk by reducing the hazard potential or consequences. The study considers how regulations may fully, partially, or inadequately mitigate the consequences of a given hazard. If development is to continue at its current pace in North East BC, it is imperative that decision-makers recognize the changing risk and resilience profiles and respond with appropriate policy. A critical component of the study comprises a gap analysis of current regulation and a possible path forward.

Development of physiotherapy inherent requirement statements – an Australian experience

PubMed Central

2013-01-01

Background The United Nations Convention on the Rights of People with Disabilities promotes equal rights of people with a disability in all aspects of their life including their education. In Australia, Disability Discrimination legislation underpins this Convention. It mandates that higher education providers must demonstrate that no discrimination has occurred and all reasonable accommodations have been considered and implemented, to facilitate access and inclusion for a student with a disability. The first step to meeting legislative requirements is to provide students with information on the inherent requirements of a course. This paper describes the steps which were taken to develop inherent requirement statements for a 4-year entry-level physiotherapy program at one Australian university. Case presentation Inherent requirement statements were developed using an existing framework, which was endorsed and mandated by the University. Items which described inherencies were extracted from Australian physiotherapy professional standards and statutory regulatory requirements, and units contained in the physiotherapy program. Data were integrated into the 8 prescribed domains: ethical behaviour, behavioural stability, legal, communication, cognition, sensory abilities, strength and mobility, and sustainable performance. Statements for each domain were developed using a 5-level framework (introductory statement, description of the inherent requirement, justification for inherency, characteristics of reasonable adjustments and exemplars) and reviewed by a University Review Panel. Refinement of statements continued until no further changes were required. Fifteen physiotherapy inherent requirement statements were developed. The eight domains identified in the existing framework, developed for Nursing, were relevant to the study of physiotherapy. Conclusions The inherent requirement statements developed in this study provide a transparent, defensible position on the current requirements of physiotherapy study at one Australian university. These statements are transferable to other physiotherapy programs in Australia due to standardised physiotherapy accreditation requirements. The model and framework could be applied to other health professional courses and used to explore the physiotherapy inherent requirements from an international perspective. PMID:23590219

National French survey on tele-transmission of EEG recordings: More than a simple technological challenge.

PubMed

Sauleau, Paul; Despatin, Jane; Cheng, Xufei; Lemesle, Martine; Touzery-de Villepin, Anne; N'Guyen The Tich, Sylvie; Kubis, Nathalie

2016-04-01

Assessment of current practice and the need for tele-transmission and remote interpretation of EEG in France. Transmission of EEG to a distant center could be a promising solution to the problem of decreasing availability of neurophysiologists for EEG interpretation, in order to provide equity within health care services in France. This practice should logically follow the legal framework of telemedicine and the recommendations that were recently edited by the Société de neurophysiologie clinique de langue française (SNCLF) and the Ligue française contre l'épilepsie (LCFE). A national survey was designed and performed under the auspices of the SNCLF. This survey reveals that there is an important gap between the official recommendations and the "reality on the ground". These local organizations were mainly established through the impulse of individual initiatives, rarely driven by health regulatory authorities and sometimes far from legal frameworks. For the majority, they result from a need to improve medical care, especially in pediatrics and neonatology, and to ensure continuity of care. When present, tele-transmission of EEG is often only partially satisfactory, since many technical procedures have to be improved. Conversely, the lack of tele-transmission of EEG would penalize medical care for some patients. The survey shows both the wealth of local initiatives and the fragility of most existing networks, emphasizing the need for better cooperation between regulatory authorities and health care professionals to establish or improve the transmission of EEG in France. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Coordination of the EMS system: an organizational theory approach.

PubMed

Narad, R A

1998-01-01

Emergency medical services (EMS) systems include autonomous organizations with high degrees of interdependence. The need to coordinate system participants has long been recognized but seldom achieved. This can be explained by organizational theory--specifically, the study of the relationships among organizations. Existing models identify the total system's functions, but fail to explain roles and relationships among the system's participants. Coordination among organizations is more difficult than coordination within an organization because of lack of an authority structure. The EMS system can be described as "a functionally interdependent system," consisting of multiple autonomous organizations with high degrees of interdependence in their technical functions. Communities have five potential management approaches, varying according to their aggressiveness. These are laissez-faire, where even voluntary coordination efforts are not tried; voluntary cooperation efforts, such as coordinating councils; external planning agencies without regulatory control; "framework organizations" with regulatory control over the system participants; and bureaucratization, placing the system participants within a single organizational hierarchy. The "multicratic organization" is a model for management of multiorganizational systems. A "system lead agency" plans joint activities and manages relationships among system participants in the way that the management of a uniorganization integrates departments. A lead agency is usually a unit of government or organized pursuant to government action, but a managed care organization can also fill this role. In extreme application of the model, the system is viewed as a framework and temporary modules are attached. Their interests are limited, as needed, to optimize the entire system. The lead agency sets policies affecting relationships of modules and policies crossing organizational boundaries.

Strengths, weaknesses and future challenges of biosimilars' development. An opinion on how to improve the knowledge and use of biosimilars in clinical practice.

PubMed

Scavone, Cristina; Rafaniello, Concetta; Berrino, Liberato; Rossi, Francesco; Capuano, Annalisa

2017-12-01

Biosimilars started receiving the marketing authorization by European Medicine Agency since 2006. The development of biosimilars follows a well-defined step-wise approach, the so-called comparability exercise, which aims to compare non-clinical (mainly quality features and biological activity) and clinical (efficacy and safety profiles) features of new biosimilars with their respective reference products. Despite the undeniable advantages of such procedure, some concerns (such as the absence of switching studies or the evaluation of efficacy and safety in all therapeutic indications) still exist about its. In particular, the European regulatory framework on biosimilars approval does not include the conduction of switching studies demonstrating the interchangeability to be carried out before marketing authorization. This is one of the main aspects that negatively affects healthcare professionals' clinical decisions on switch. In order to achieve a better knowledge on safety and efficacy of biosimilar drugs, real world data should be collected and post-marketing efficacy and safety clinical studies (including those evaluating specific endpoints, therapeutic regimens and patients population), should be planned. also the conduction of well-designed switching studies is highly advisable, especially in the case of biosimilar drugs used in oncology settings. Lastly, considering the critical role of antidrug antibodies on efficacy/safety profile of biologic drugs, studies based on therapeutic drug monitoring would be useful in order to achieve treatment optimization. Implementing the above strategies could be helpful to fill the gap in knowledge observed in the present European biosimilar regulatory framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

Migrants and emerging public health issues in a globalized world: threats, risks and challenges, an evidence-based framework

PubMed Central

Gushulak, BD; Weekers, J; MacPherson, DW

2010-01-01

International population mobility is an underlying factor in the emergence of public health threats and risks that must be managed globally. These risks are often related, but not limited, to transmissible pathogens. Mobile populations can link zones of disease emergence to lowprevalence or nonendemic areas through rapid or high-volume international movements, or both. Against this background of human movement, other global processes such as economics, trade, transportation, environment and climate change, as well as civil security influence the health impacts of disease emergence. Concurrently, global information systems, together with regulatory frameworks for disease surveillance and reporting, affect organizational and public awareness of events of potential public health significance. International regulations directed at disease mitigation and control have not kept pace with the growing challenges associated with the volume, speed, diversity, and disparity of modern patterns of human movement. The thesis that human population mobility is itself a major determinant of global public health is supported in this article by review of the published literature from the perspective of determinants of health (such as genetics/biology, behavior, environment, and socioeconomics), population-based disease prevalence differences, existing national and international health policies and regulations, as well as inter-regional shifts in population demographics and health outcomes. This paper highlights some of the emerging threats and risks to public health, identifies gaps in existing frameworks to manage health issues associated with migration, and suggests changes in approach to population mobility, globalization, and public health. The proposed integrated approach includes a broad spectrum of stakeholders ranging from individual health-care providers to policy makers and international organizations that are primarily involved in global health management, or are influenced by global health events. PMID:22460280

Migrants and emerging public health issues in a globalized world: threats, risks and challenges, an evidence-based framework.

PubMed

Gushulak, Bd; Weekers, J; Macpherson, Dw

2009-01-01

International population mobility is an underlying factor in the emergence of public health threats and risks that must be managed globally. These risks are often related, but not limited, to transmissible pathogens. Mobile populations can link zones of disease emergence to lowprevalence or nonendemic areas through rapid or high-volume international movements, or both. Against this background of human movement, other global processes such as economics, trade, transportation, environment and climate change, as well as civil security influence the health impacts of disease emergence. Concurrently, global information systems, together with regulatory frameworks for disease surveillance and reporting, affect organizational and public awareness of events of potential public health significance. International regulations directed at disease mitigation and control have not kept pace with the growing challenges associated with the volume, speed, diversity, and disparity of modern patterns of human movement. The thesis that human population mobility is itself a major determinant of global public health is supported in this article by review of the published literature from the perspective of determinants of health (such as genetics/biology, behavior, environment, and socioeconomics), population-based disease prevalence differences, existing national and international health policies and regulations, as well as inter-regional shifts in population demographics and health outcomes. This paper highlights some of the emerging threats and risks to public health, identifies gaps in existing frameworks to manage health issues associated with migration, and suggests changes in approach to population mobility, globalization, and public health. The proposed integrated approach includes a broad spectrum of stakeholders ranging from individual health-care providers to policy makers and international organizations that are primarily involved in global health management, or are influenced by global health events.

Regulatory constraints as seen from the pharmaceutical industry.

PubMed

Galligani, G; David-Andersen, I; Fossum, B

2005-01-01

In Chile, Canada, Europe, Japan, and the USA, which are the main geographical areas for fish farming of high value fish such as salmonids, sea bass, sea bream, yellowtail and catfish, vaccination has been established as an important method for the prevention of infectious diseases. To make new vaccines available to the fish farming industry, pharmaceutical companies must comply with the regulatory framework for licensing of fish vaccines, which in recent years has become more regulated. Considerable scientific and regulatory skills are thus required to develop, document and license vaccines in accordance with the requirements in the different geographical areas. International co-operation to harmonise requirements for the licensing documentation is ongoing. Even though there are obvious benefits to the pharmaceutical industry from the harmonisation process, it may sometimes impose unreasonable requirements. The regulatory framework for fish vaccines clearly has an impact on the time for bringing a new fish vaccine to the market. Several hurdles need to be passed to complete the regulatory process, i.e. obtain a licence. Fulfilment of the rather detailed and extensive requirements for documentation of the production and controls, as well as safety and efficacy of the vaccine, represent a challenge to the pharmaceutical industry, as do the different national and regional licensing procedures. This paper describes regulatory constraints related to the documentation, the licensing process, the site of production and the continuing international harmonisation work, with emphasis on inactivated conventional fish vaccines.

Federal/State Regulatory Enhancement, Cost Allocation, and CATV/TELCO Distance Learning Initiatives in Connecticut.

ERIC Educational Resources Information Center

Pietras, Jesse John

Connecticut has adopted a moderate approach to communications infrastructure modernization, covering a 4-year implementation period from 1993 to 1996. The state's remote educational framework, with regulatory enhancements, will allow the state to be technologically competitive with neighboring states as it allows subscribers to use evolving…

77 FR 45700 - Advisory Committee On Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee On Fukushima...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... NUCLEAR REGULATORY COMMISSION Advisory Committee On Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee On Fukushima; Notice of Meeting The ACRS Subcommittee on Fukushima will hold a meeting on August... Fukushima Near Term Task Force (NTTF) Recommendation 1: Enhanced Regulatory Framework. The Subcommittee will...

Self-Regulatory Climate: A Positive Attribute of Public Schools

ERIC Educational Resources Information Center

Adams, Curt M.; Ware, Jordan K.; Miskell, Ryan C.; Forsyth, Patrick B.

2016-01-01

This study contributes to the development of a positive framework for effective public schools in 2 ways. First, it advances the construct self-regulatory climate as consisting of 3 generative school norms--collective faculty trust in students, collective student trust in teachers, and student-perceived academic emphasis. The authors argue these…

Accessing the medical devices market in Egypt and Saudi Arabia: a systematic review of policies and regulations.

PubMed

Gad, Mohamed; Kriza, Christine; Fidler, Armin; Kolominsky-Rabas, Peter

2016-07-01

Despite the significant medical devices market size in Egypt and Saudi Arabia, information regarding policies and regulations for medical devices market access is highly deficient. The aim of this paper is to provide a systematic review on market access policies and regulations in both countries, to allow safe and timely access to medical technology. The following databases were searched: PubMed, Science Direct, Scopus, and Al Manhal Arabic database. Additionally, the web portals of regulatory authorities of both countries were searched. There are 34 records included in the qualitative synthesis of this review. Expert commentary: Main findings include; adopted regulatory framework from reference countries, and interim main regulatory documents, In conclusion, the market access schemes are relatively structured. However, some recommendations are put forward to navigate towards a more comprehensive policy framework in both countries.

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

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

NONE

1996-07-01

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

Multimodal Freight Transport Regulations in Indonesia And Its Implementation (A Case Study of Tanjung Priok Port)

NASA Astrophysics Data System (ADS)

Budisiswanto, N.; Miharja, M.; Kombaitan, B.; Pradono, P.

2018-05-01

The purpose of this paper is to present the current situation of multimodal transport in Indonesia and the various ways in which it is implemented. This paper will also examine the existing regulations and overcome barriers in implementation for providers and users of services. The paper also aims to correlate the elements of government regulation into the logistics chain, to understand the need for the application of Multimodal Transport. Indonesia has realized the benefits that can be achieved by implementing multimodal transport, an important alternative to improve logistics performance. As the government plays an important role in offering the legal and institutional framework, this paper assesses the implementation of regulatory linkages, infrastructure, and why multimodal transport is still not implemented properly.

Teaching civility to undergraduate nursing students using a virtue ethics-based curriculum.

PubMed

Russell, Martha Joan

2014-06-01

As professionals, nurses are expected to engage in respectful relationships with clients, other health care professionals, and each other. Regulatory bodies set standards and codes of ethics for professional behavior in nursing that clearly communicate expectations for civility. However, the wealth of literature on incivility in the profession indicates that nurses often fall short of meeting these standards in their interactions with other nurses. Currently, few effective strategies exist for nurse educators to teach civility to nursing students and prepare them to engage in healthy relationships with their colleagues. This article argues for the use of virtue ethics as a philosophical framework for teaching civility to undergraduate nursing students. The pedagogical strategies proposed may help students contribute to the development of healthy workplaces. Copyright 2014, SLACK Incorporated.

Paperless clinical trials: Myth or reality?

PubMed Central

Gupta, Sandeep K.

2015-01-01

There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

Generic drugs: international trends and policy developments in Australia.

PubMed

Lofgren, Hans

2004-01-01

Public and private third-party payers in many countries encourage or mandate the use of generic drugs. This article examines the development of generics policy in Australia, against the background of a description of international trends in this area, and related experiences of reference pricing programs. The Australian generics market remains underdeveloped due to a historical legacy of small Pharmaceutical Benefits Scheme price differentials between originator brands and generics. It is argued that policy measures open to the Australian government can be conceived as clustering around two different approaches: incremental changes within the existing regulatory framework, or a shift towards a high volume/low price role of generics which would speed up the delivery of substantial cost savings, and could provide enhanced scope for the financing of new, patented drugs.

Transnational gestational surrogacy: does it have to be exploitative?

PubMed

Kirby, Jeffrey

2014-01-01

This article explores the controversial practice of transnational gestational surrogacy and poses a provocative question: Does it have to be exploitative? Various existing models of exploitation are considered and a novel exploitation-evaluation heuristic is introduced to assist in the analysis of the potentially exploitative dimensions/elements of complex health-related practices. On the basis of application of the heuristic, I conclude that transnational gestational surrogacy, as currently practiced in low-income country settings (such as rural, western India), is exploitative of surrogate women. Arising out of consideration of the heuristic's exploitation conditions, a set of public education and enabled choice, enhanced protections, and empowerment reforms to transnational gestational surrogacy practice is proposed that, if incorporated into a national regulatory framework and actualized within a low income country, could possibly render such practice nonexploitative.

Professionalism in Vocational Education: International Perspectives

ERIC Educational Resources Information Center

Atkins, Liz; Tummons, Jonathan

2017-01-01

This paper explores notions of professionalism amongst vocational teachers in the United Kingdom and Australia, through an analysis of voluntarism/regulatory frameworks and professional body frameworks. In terms of empirical evidence, the paper reports on data drawn from a documentary analysis of government policy documents, standards for the…

Application of the adverse outcome pathway framework - advances and challenges

EPA Science Inventory

The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

NEWS RELEASE - Agencies Agree to Joint Regulatory Framework for Processing Applications for Surface Coal Mining Operations

EPA Pesticide Factsheets

News release from February 10, 2005 announcing a memorandum of understanding (MOU) that offers a joint framework to improve permit application procedures for surface coal mining operations that place dredged or fill material in waters of the United States.

A Framework for Measuring the Economic Benefits of Ground Water (1995)

EPA Pesticide Factsheets

The primary goal of this 1995 report is to develop a framework for assessing the economic value of ground water that is applicable to all offices within U.S. EPA that consider the value of ground water resources when conducting Regulatory Impact Analyses

Development of an acute oral toxicity dataset to facilitate assessment of existing QSARs and development of new models (WC10)

EPA Science Inventory

Acute oral toxicity data are used to meet both regulatory and non-regulatory needs. Recently, there have been efforts to explore alternative approaches for predicting acute oral toxicity such as QSARs. Evaluating the performance and scope of existing models and investigating the ...

Toward the framework and implementation for clearance of materials from regulated facilities.

PubMed

Chen, S Y; Moeller, D W; Dornsife, W P; Meyer, H R; Lamastra, A; Lubenau, J O; Strom, D J; Yusko, J G

2005-08-01

The disposition of solid materials from nuclear facilities has been a subject of public debate for several decades. The primary concern has been the potential health effects resulting from exposure to residual radioactive materials to be released for unrestricted use. These debates have intensified in the last decade as many regulated facilities are seeking viable management decisions on the disposition of the large amounts of materials potentially containing very low levels of residual radioactivity. Such facilities include the nuclear weapons complex sites managed by the U.S. Department of Energy, commercial power plants licensed by the U.S. Nuclear Regulatory Commission (NRC), and other materials licensees regulated by the NRC or the Agreement States. Other facilities that generate radioactive material containing naturally occurring radioactive materials (NORM) or technologically enhanced NORM (TENORM) are also seeking to dispose of similar materials that may be radioactively contaminated. In contrast to the facilities operated by the DOE and the nuclear power plants licensed by the U.S. Nuclear Regulatory Commission, NORM and TENORM facilities are regulated by the individual states. Current federal laws and regulations do not specify criteria for releasing these materials that may contain residual radioactivity of either man-made or natural origin from regulatory controls. In fact, the current regulatory scheme offers no explicit provision to permit materials being released as "non-radioactive," including those that are essentially free of contamination. The only method used to date with limited success has been case-by-case evaluation and approval. In addition, there is a poorly defined and inconsistent regulatory framework for regulating NORM and TENORM. Some years ago, the International Atomic Energy Agency introduced the concept of clearance, that is, controlling releases of any such materials within the regulatory domain. This paper aims to clarify clearance as an important disposition option for solid materials, establish the framework and basis of release, and discuss resolutions regarding the implementation of such a disposition option.

Climate change adaptation in regulated water utilities

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

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

PubMed

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

2016-10-01

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

Reassessing policy paradigms: A comparison of the global tobacco and alcohol industries.

PubMed

Hawkins, Benjamin; Holden, Chris; Eckhardt, Jappe; Lee, Kelley

2018-01-01

Tobacco is widely considered to be a uniquely harmful product for human health. Since the mid-1990s, the strategies of transnational tobacco corporations to undermine effective tobacco control policy has been extensively documented through internal industry documents. Consequently, the sale, use and marketing of tobacco products are subject to extensive regulation and formal measures to exclude the industry from policy-making have been adopted in the Framework Convention on Tobacco Control. In contrast to tobacco, alcohol is subject to less stringent forms of regulation, and the alcohol industry continues to play a central role in policy-making in many countries and at the global level. This article examines whether there is a sufficient rationale for such different regulatory approaches, through a comparative analysis of the political economy of the tobacco and alcohol industries including the structure of the industries, and the market and political strategies they pursue. Despite some important differences, the extensive similarities which exist between the tobacco and alcohol industries in terms of market structure and strategy, and political strategy, call into question the rationale for both the relatively weak regulatory approach taken towards alcohol, and the continued participation of alcohol corporations in policy-making processes.

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

PubMed

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

2017-12-01

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

The roles of patents and research and development incentives in biopharmaceutical innovation.

PubMed

Grabowski, Henry G; DiMasi, Joseph A; Long, Genia

2015-02-01

Patents and other forms of intellectual property protection play essential roles in encouraging innovation in biopharmaceuticals. As part of the "21st Century Cures" initiative, Congress is reviewing the policy mechanisms designed to accelerate the discovery, development, and delivery of new treatments. Debate continues about how best to balance patent and intellectual property incentives to encourage innovation, on the one hand, and generic utilization and price competition, on the other hand. We review the current framework for accomplishing these dual objectives and the important role of patents and regulatory exclusivity (together, the patent-based system), given the lengthy, costly, and risky biopharmaceutical research and development process. We summarize existing targeted incentives, such as for orphan drugs and neglected diseases, and we consider the pros and cons of proposed voluntary or mandatory alternatives to the patent-based system, such as prizes and government research and development contracting. We conclude that patents and regulatory exclusivity provisions are likely to remain the core approach to providing incentives for biopharmaceutical research and development. However, prizes and other voluntary supplements could play a useful role in addressing unmet needs and gaps in specific circumstances. Project HOPE—The People-to-People Health Foundation, Inc.

SAFEGUARD: An Assured Safety Net Technology for UAS

NASA Technical Reports Server (NTRS)

Dill, Evan T.; Young, Steven D.; Hayhurst, Kelly J.

2016-01-01

As demands increase to use unmanned aircraft systems (UAS) for a broad spectrum of commercial applications, regulatory authorities are examining how to safely integrate them without loss of safety or major disruption to existing airspace operations. This work addresses the development of the Safeguard system as an assured safety net technology for UAS. The Safeguard system monitors and enforces conformance to a set of rules defined prior to flight (e.g., geospatial stay-out or stay-in regions, speed limits, altitude limits). Safeguard operates independently of the UAS autopilot and is strategically designed in a way that can be realized by a small set of verifiable functions to simplify compliance with regulatory standards for commercial aircraft. A framework is described that decouples the system from any other devices on the UAS as well as introduces complementary positioning source(s) for applications that require integrity and availability beyond what the Global Positioning System (GPS) can provide. Additionally, the high level logic embedded within the software is presented, as well as the steps being taken toward verification and validation (V&V) of proper functionality. Next, an initial prototype implementation of the described system is disclosed. Lastly, future work including development, testing, and system V&V is summarized.

Drug policy and global regulatory capitalism: the case of new psychoactive substances (NPS).

PubMed

Seddon, Toby

2014-09-01

The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism. Copyright © 2014 Elsevier B.V. All rights reserved.

Facilitating the appropriate use of e-health solutions.

PubMed

Stern, Hartley S; Ceresia, Patrick; Lapner, Martin

2014-01-01

In this issue, the lead article proposes that e-health technologies should be used more broadly and that patients should have greater access to their information through such technologies. The Canadian Medical Protective Association (CMPA) agrees with this statement and suggests that to facilitate the timely and appropriate adoption of new technologies among healthcare providers to enhance patient care, barriers in the existing regulatory, legislative and legal frameworks must be addressed. While much of the discussion to date on e-health has focused primarily on high-level issues regarding regulatory compliance, "privacy by design" and the e-health "panacea," CMPA suggests that there needs to be a refocus on achieving more concrete change and gains through consideration of the specific impact on the drivers of healthcare delivery. An integrated or holistic approach is required involving healthcare providers, regulators, legislators, stakeholders, ministries of health, privacy commissioners and the courts. To better leverage potential advantages, efficiencies and enhanced, safer care for our healthcare system, all parties must work together to develop an acceptable and flexible approach to the "appropriate use" of e-health technologies that will facilitate adoption by healthcare professionals in a manner that is consistent with the expectations of the profession and applicable standards of practice.

PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation

PubMed Central

Portales-Casamar, Elodie; Kirov, Stefan; Lim, Jonathan; Lithwick, Stuart; Swanson, Magdalena I; Ticoll, Amy; Snoddy, Jay; Wasserman, Wyeth W

2007-01-01

PAZAR is an open-access and open-source database of transcription factor and regulatory sequence annotation with associated web interface and programming tools for data submission and extraction. Curated boutique data collections can be maintained and disseminated through the unified schema of the mall-like PAZAR repository. The Pleiades Promoter Project collection of brain-linked regulatory sequences is introduced to demonstrate the depth of annotation possible within PAZAR. PAZAR, located at , is open for business. PMID:17916232

PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation.

PubMed

Portales-Casamar, Elodie; Kirov, Stefan; Lim, Jonathan; Lithwick, Stuart; Swanson, Magdalena I; Ticoll, Amy; Snoddy, Jay; Wasserman, Wyeth W

2007-01-01

PAZAR is an open-access and open-source database of transcription factor and regulatory sequence annotation with associated web interface and programming tools for data submission and extraction. Curated boutique data collections can be maintained and disseminated through the unified schema of the mall-like PAZAR repository. The Pleiades Promoter Project collection of brain-linked regulatory sequences is introduced to demonstrate the depth of annotation possible within PAZAR. PAZAR, located at http://www.pazar.info, is open for business.

Regulatory frameworks for mobile medical applications.

PubMed

Censi, Federica; Mattei, Eugenio; Triventi, Michele; Calcagnini, Giovanni

2015-05-01

A mobile application (app) is a software program that runs on mobile communication devices such as a smartphone. The concept of a mobile medical app has gained popularity and diffusion but its reference regulatory context has raised discussion and concerns. Theoretically, a mobile app can be developed and uploaded easily by any person or entity. Thus, if an app can have some effects on the health of the users, it is mandatory to identify its reference regulatory context and the applicable prescriptions.

Consultation: Professional Learning Framework for the Teaching Profession.

ERIC Educational Resources Information Center

Ontario College of Teachers, Toronto.

This publication describes the professional learning framework for teaching that was developed by the Ontario College of Teachers, a self-regulatory body for the teaching profession in Ontario. The Ontario College of Teachers has a mandate, in legislation, to identify and accredit professional learning programs that support standards of practice…

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

PubMed

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

2015-07-01

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

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

PubMed

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

2012-04-01

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

Cancer drug development and the evolving regulatory framework for companion diagnostics in the European union.

PubMed

Pignatti, Francesco; Ehmann, Falk; Hemmings, Robert; Jonsson, Bertil; Nuebling, Micha; Papaluca-Amati, Marisa; Posch, Martin; Rasi, Guido

2014-03-15

The European Union (EU) legal framework for medical device regulation is currently under revision. The European Commission has proposed a new framework to ensure that medical devices serve the needs and ensure the safety of European citizens, aiming for a framework that is fit for purpose, more transparent, and better adapted to scientific and technological progress. The proposed new framework is described as an evolution of the current regime keeping the same legal approach. An important proposed change is that companion diagnostics will no longer be considered as low risk and subject to self-certification by the manufacturer. According to the new proposal, companion diagnostics will be classified as high individual risk or moderate public health risk (category C) and require conformity assessment by a notified body. It has also been proposed that evidence of the clinical utility of the device for the intended purpose should be required for companion diagnostics. In this article, we review the EU legal framework relevant for companion diagnostics, describe the proposed changes, and summarize the available scientific guidance from the European Medicines Agency and its regulatory experience with cancer drug development including companion diagnostics. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

The Pollution Game: A Classroom Game Demonstrating the Relative Effectiveness of Emissions Taxes and Tradable Permits

ERIC Educational Resources Information Center

Corrigan, Jay R.

2011-01-01

This classroom game illustrates the strengths and weaknesses of various regulatory frameworks aimed at internalizing negative externalities from pollution. Specifically, the game divides students into three groups--a government regulatory agency and two polluting firms--and allows them to work through a system of uniform command-and-control…

"Body Work--Regulation of a Swimmer Body": An Autoethnography from an Australian Elite Swimmer

ERIC Educational Resources Information Center

McMahon, Jenny; DinanThompson, Maree

2011-01-01

This paper contributes to studies on sociology and the body by exploring my bodily experiences as an Australian elite swimmer in an autoethnographic framework. More specifically, it focuses on the relationship between the regulatory practices of others on my body and my development of self-regulatory practices. The stories in this paper reveal…

Boolean network inference from time series data incorporating prior biological knowledge.

PubMed

Haider, Saad; Pal, Ranadip

2012-01-01

Numerous approaches exist for modeling of genetic regulatory networks (GRNs) but the low sampling rates often employed in biological studies prevents the inference of detailed models from experimental data. In this paper, we analyze the issues involved in estimating a model of a GRN from single cell line time series data with limited time points. We present an inference approach for a Boolean Network (BN) model of a GRN from limited transcriptomic or proteomic time series data based on prior biological knowledge of connectivity, constraints on attractor structure and robust design. We applied our inference approach to 6 time point transcriptomic data on Human Mammary Epithelial Cell line (HMEC) after application of Epidermal Growth Factor (EGF) and generated a BN with a plausible biological structure satisfying the data. We further defined and applied a similarity measure to compare synthetic BNs and BNs generated through the proposed approach constructed from transitions of various paths of the synthetic BNs. We have also compared the performance of our algorithm with two existing BN inference algorithms. Through theoretical analysis and simulations, we showed the rarity of arriving at a BN from limited time series data with plausible biological structure using random connectivity and absence of structure in data. The framework when applied to experimental data and data generated from synthetic BNs were able to estimate BNs with high similarity scores. Comparison with existing BN inference algorithms showed the better performance of our proposed algorithm for limited time series data. The proposed framework can also be applied to optimize the connectivity of a GRN from experimental data when the prior biological knowledge on regulators is limited or not unique.

[European Marketing Authorisation: a long process. Experiences of small biotech companies with the ATMP regulation].

PubMed

Buljovčić, Z

2011-07-01

On 30 December 2008, the Regulation (EC) 1394/2007 on advanced therapy medicinal products (ATMPs) entered into force. Herewith the first EU-wide regulatory framework for ATMPs was established. It requires a central marketing authorisation application to the EMA (European Medicinal Agency). This new framework especially changes the code of regulatory practice for tissue engineered products (TEPs), as no registration procedure had been previously required for autologous TEPs. This also meant that no clinical proof of efficacy achieved by a pivotal clinical trial was necessary. Difficulties and their background as well as the vast requirements for product development that have to be addressed by small companies within a very short time frame are presented. Hereby, it is obvious that regulatory experience which is required to identify and implement the resulting implications was not in place yet and still had to be established. The lack of regulatory experience also resulted in difficulties with scientific advice preparation, expectations toward regulatory agencies, consultants, and transformation of regulatory requirements. Addressing the regulatory requirements within the transition period is even more difficult for entrepreneurs with products which are assigned for indications resulting in complex challenges to the trial design. Due to the enormous time pressure to generate data and due to the implied financial pressure, different adaptation strategies are evolving. In Germany the "hospital exemption" according to §4b AMG (German Medicinal Products Law) is of major importance. A reorientation toward acellular products and a slow down in development of new ATMP products is expected.

Genetically modified organisms: an analysis of the regulatory framework currently employed within the European Union.

PubMed

Gent, R N

1999-09-01

Genetic engineering technology is starting to bring many commercial products to the market. These genetically modified organisms (GMOs) and their derived products are subject to topical debate as to their benefits and risks. The strengths and weaknesses of the regulatory framework that controls their development and application is central to the question of whether this technology poses significant risk to the public health during this critical phase of its evolution. A critical review was carried out of the legal framework regulating the contained use, deliberate release and some aspects of consumer protection relevant to the control of GMOs in Europe and the United Kingdom. The current legal framework is failing to provide a speed of adaptation commensurate with the development of the science of genetic engineering; failing to properly respond to democratic control; failing to resolve significant conflict between the protection of free markets and protection of public health and the environment; and failing to implement obligations on biodiversity. The present legal framework must be replaced. Current European Union proposals for new standards of regulation are welcome, but provide only for further incremental change, and do not address some significant fundamental flaws in our current laws.

A Sparse Reconstruction Approach for Identifying Gene Regulatory Networks Using Steady-State Experiment Data

PubMed Central

Zhang, Wanhong; Zhou, Tong

2015-01-01

Motivation Identifying gene regulatory networks (GRNs) which consist of a large number of interacting units has become a problem of paramount importance in systems biology. Situations exist extensively in which causal interacting relationships among these units are required to be reconstructed from measured expression data and other a priori information. Though numerous classical methods have been developed to unravel the interactions of GRNs, these methods either have higher computing complexities or have lower estimation accuracies. Note that great similarities exist between identification of genes that directly regulate a specific gene and a sparse vector reconstruction, which often relates to the determination of the number, location and magnitude of nonzero entries of an unknown vector by solving an underdetermined system of linear equations y = Φx. Based on these similarities, we propose a novel framework of sparse reconstruction to identify the structure of a GRN, so as to increase accuracy of causal regulation estimations, as well as to reduce their computational complexity. Results In this paper, a sparse reconstruction framework is proposed on basis of steady-state experiment data to identify GRN structure. Different from traditional methods, this approach is adopted which is well suitable for a large-scale underdetermined problem in inferring a sparse vector. We investigate how to combine the noisy steady-state experiment data and a sparse reconstruction algorithm to identify causal relationships. Efficiency of this method is tested by an artificial linear network, a mitogen-activated protein kinase (MAPK) pathway network and the in silico networks of the DREAM challenges. The performance of the suggested approach is compared with two state-of-the-art algorithms, the widely adopted total least-squares (TLS) method and those available results on the DREAM project. Actual results show that, with a lower computational cost, the proposed method can significantly enhance estimation accuracy and greatly reduce false positive and negative errors. Furthermore, numerical calculations demonstrate that the proposed algorithm may have faster convergence speed and smaller fluctuation than other methods when either estimate error or estimate bias is considered. PMID:26207991

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

PubMed

Madden, Edward A

2007-02-01

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

Reverse-engineering of gene networks for regulating early blood development from single-cell measurements.

PubMed

Wei, Jiangyong; Hu, Xiaohua; Zou, Xiufen; Tian, Tianhai

2017-12-28

Recent advances in omics technologies have raised great opportunities to study large-scale regulatory networks inside the cell. In addition, single-cell experiments have measured the gene and protein activities in a large number of cells under the same experimental conditions. However, a significant challenge in computational biology and bioinformatics is how to derive quantitative information from the single-cell observations and how to develop sophisticated mathematical models to describe the dynamic properties of regulatory networks using the derived quantitative information. This work designs an integrated approach to reverse-engineer gene networks for regulating early blood development based on singel-cell experimental observations. The wanderlust algorithm is initially used to develop the pseudo-trajectory for the activities of a number of genes. Since the gene expression data in the developed pseudo-trajectory show large fluctuations, we then use Gaussian process regression methods to smooth the gene express data in order to obtain pseudo-trajectories with much less fluctuations. The proposed integrated framework consists of both bioinformatics algorithms to reconstruct the regulatory network and mathematical models using differential equations to describe the dynamics of gene expression. The developed approach is applied to study the network regulating early blood cell development. A graphic model is constructed for a regulatory network with forty genes and a dynamic model using differential equations is developed for a network of nine genes. Numerical results suggests that the proposed model is able to match experimental data very well. We also examine the networks with more regulatory relations and numerical results show that more regulations may exist. We test the possibility of auto-regulation but numerical simulations do not support the positive auto-regulation. In addition, robustness is used as an importantly additional criterion to select candidate networks. The research results in this work shows that the developed approach is an efficient and effective method to reverse-engineer gene networks using single-cell experimental observations.

NEGOTIATING STRUCTURAL VULNERABILITY FOLLOWING REGULATORY CHANGES TO A PROVINCIAL METHADONE PROGRAM IN VANCOUVER, CANADA: A QUALITATIVE STUDY

PubMed Central

McNeil, Ryan; Kerr, Thomas; Anderson, Solanna; Maher, Lisa; Keewatin, Chereece; Milloy, MJ; Wood, Evan; Small, Will

2015-01-01

While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of socialstructural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose® (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analyzed thematically, and by drawing on the concept of ‘structural vulnerability’. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose® precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and codispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug use and participation in high-risk incomegenerating strategies. Greater attention to the impacts of social-structural inequities on MMT engagement is needed when modifying MMT programs, especially as other jurisdictions are adopting similar changes. Comprehensive environmental supports should be provided to minimize adverse outcomes during transitional periods. PMID:25875323

Working towards an integrated land contamination management framework for Nigeria.

PubMed

Sam, Kabari; Coulon, Frédéric; Prpich, George

2016-11-15

Over the past five decades, Nigeria has developed a number of contaminated land legislations to address the damage caused primarily by oil and gas exploitation activities. Within these legislations exists elements of risk assessment and risk-based corrective action. Despite this progress, we argue that contaminated land management approaches in Nigeria need further development to be able to integrate new scientific information, and to address environmental, economic, and social values. By comparison, advanced contaminated land regimes in the United Kingdom (UK), the Netherlands, Australia, New Zealand, and the United States of America (USA) apply a number of integrative approaches (e.g. sustainability appraisal, liability regime, funding mechanisms, technology demonstration) that enable them to meet the environmental, economic, and social needs of their populations. In comparison, Nigerian governance lacks many of these mechanisms and management of contaminated land is ad hoc. In this paper we propose an integrated risk assessment framework for Nigeria that incorporates the principles of sustainability and stakeholder engagement into the decision-making processes for contaminated land risk assessment and risk management. The integrated approach relies on transparency to promote acceptance and build trust in institutions, and uses stakeholder engagement to address data deficiencies. We conclude this paper with a roadmap for how Nigeria might implement such an integrative approach into their existing contaminated land regulatory system, as well as identify a series of policy priorities that should be addressed. Copyright © 2016 Elsevier B.V. All rights reserved.

The cost of harmful alcohol use in South Africa.

PubMed

Matzopoulos, R G; Truen, S; Bowman, B; Corrigall, J

2014-02-01

The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa. We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from secondary sources. Care was taken to avoid possible causes of cost overestimation, in particular double counting and, as far as possible, second-round effects of alcohol abuse. The combined total tangible and intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the 2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP. The costs of alcohol-related harms provide a substantial counterbalance to the economic benefits highlighted by the alcohol industry to counter stricter regulation. Curtailing these costs by regulatory and policy interventions contributes directly and indirectly to social well-being and the economy. CONCLUSIONS; Existing frameworks that guide the regulation and distribution of alcohol frequently focus on maximising the contribution of the alcohol sector to the economy, but should also take into account the associated economic, social and health costs. Current interventions do not systematically address the most important causes of harm from alcohol, and need to be informed by reliable evidence of the ongoing costs of alcohol-related harms.

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

PubMed Central

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

2014-01-01

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

Applying gene regulatory network logic to the evolution of social behavior.

PubMed

Baran, Nicole M; McGrath, Patrick T; Streelman, J Todd

2017-06-06

Animal behavior is ultimately the product of gene regulatory networks (GRNs) for brain development and neural networks for brain function. The GRN approach has advanced the fields of genomics and development, and we identify organizational similarities between networks of genes that build the brain and networks of neurons that encode brain function. In this perspective, we engage the analogy between developmental networks and neural networks, exploring the advantages of using GRN logic to study behavior. Applying the GRN approach to the brain and behavior provides a quantitative and manipulative framework for discovery. We illustrate features of this framework using the example of social behavior and the neural circuitry of aggression.

Estonian Preschool Teachers' Aspirations for Curricular Autonomy--The Gap between an Ideal and Professional Practice

ERIC Educational Resources Information Center

Tuul, Maire; Mikser, Rain; Neudorf, Evelyn; Ugaste, Aino

2015-01-01

Establishing national framework curricula is a growing tendency in early childhood education internationally, and is considered to be part of the regulatory requirements framework for enhancing preschool teachers' professionalism. A topical issue in this context is whether and how teachers themselves see these practices as contributing to their…

How can environmental regulations promote clean coal technology adoption in APEC developing economies?

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

NONE

2007-11-15

The study examines both existing and emerging regulatory frameworks in order to determine which type of regulations that would be most effective at promoting clean coal technology adoption in development Asia Pacific Economic Co-operation (APEC) economies and would be practical to implement. regulations targeting air emissions; regulations targeting water use; and regulations concerning coal combustion by-products. When considering the potential effect of existing and new environmental regulations on the adoption of clean coal the analysis of technologies was organised into three categories: environmental control technologies; high efficiency coal combustion technologies; and carbon dioxide capture and storage (CCS). To target themore » recommendations towards APEC economies that would benefit the most from this analysis, the study focused on developing and transition APEC economies that are expected to rely on coal for a large part of their future generating capacity. These economies include China, Indonesia, the Philippines, the Russian Federation, Thailand, and Vietnam. ACARP provided funding to this study, under Project C15078. 10 figs., 14 tabs., 10 apps.« less

Regulations and guidelines governing stem cell based products: Clinical considerations

PubMed Central

George, Bobby

2011-01-01

The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for “stem cell based products (SCBP)”. There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects. PMID:21897884

Antimicrobials in animal agriculture: parables and policy.

PubMed

Scott, H M; Midgley, G; Loneragan, G H

2015-04-01

In addition to the scientific, economic, regulatory and other policy factors that impact on antimicrobial decision-making in different jurisdictions around the world, there exist ethical, social and cultural bases for the contemporary use of these products in animal agriculture. Thus, the use of the word 'parable' to describe the contemporary moral stories that help to guide ethical antimicrobial use practices and broader policy decisions in animal agriculture is appropriate. Several of these stories reflect difficult decisions that arise from conflicting moral imperatives (i.e. both towards animal welfare and towards human health). Understanding the factors that combine to define the past and present paradigms of antimicrobial usage is crucial to mapping a path forward. There exist barriers, as well as opportunities, for advancing scenarios for reducing antimicrobial usage under a variety of voluntary, regulatory and legal policy frameworks. Any new approaches will ideally be structured to extend the use of present-day antimicrobials into the future, to provide novel alternatives for regulating any newly introduced antimicrobial products so as to maximize their useful life span and to ensure the optimal use of these products in animal agriculture to protect not only the health of animals and the interests of animal health/agriculture stakeholders, but also the human health and the interests of the public at large. A full range of policy approaches, which span the realm from strictly enforced regulations and laws to voluntary guidelines and compliance, should be explored with respect to their risks and benefits in a variety of worldwide settings and in full consideration of a range of stakeholder values. © 2015 Blackwell Verlag GmbH.

Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety, Efficacy, and Necessity for a New Regulatory Framework.

PubMed

Abdel-Tawab, Mona

2018-04-01

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission. Georg Thieme Verlag KG Stuttgart · New York.

Food safety security: a new concept for enhancing food safety measures.

PubMed

Iyengar, Venkatesh; Elmadfa, Ibrahim

2012-06-01

The food safety security (FSS) concept is perceived as an early warning system for minimizing food safety (FS) breaches, and it functions in conjunction with existing FS measures. Essentially, the function of FS and FSS measures can be visualized in two parts: (i) the FS preventive measures as actions taken at the stem level, and (ii) the FSS interventions as actions taken at the root level, to enhance the impact of the implemented safety steps. In practice, along with FS, FSS also draws its support from (i) legislative directives and regulatory measures for enforcing verifiable, timely, and effective compliance; (ii) measurement systems in place for sustained quality assurance; and (iii) shared responsibility to ensure cohesion among all the stakeholders namely, policy makers, regulators, food producers, processors and distributors, and consumers. However, the functional framework of FSS differs from that of FS by way of: (i) retooling the vulnerable segments of the preventive features of existing FS measures; (ii) fine-tuning response systems to efficiently preempt the FS breaches; (iii) building a long-term nutrient and toxicant surveillance network based on validated measurement systems functioning in real time; (iv) focusing on crisp, clear, and correct communication that resonates among all the stakeholders; and (v) developing inter-disciplinary human resources to meet ever-increasing FS challenges. Important determinants of FSS include: (i) strengthening international dialogue for refining regulatory reforms and addressing emerging risks; (ii) developing innovative and strategic action points for intervention {in addition to Hazard Analysis and Critical Control Points (HACCP) procedures]; and (iii) introducing additional science-based tools such as metrology-based measurement systems.

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

ERIC Educational Resources Information Center

Comptroller General of the U.S., Washington, DC.

The Federal Communications Commission's (FCC's) program for regulating domestic telecommunications common carriers is assessed in this report, and several recommendations are made to the Congress and the FCC for improving the regulatory framework provided by the Communications Act of 1934. A digest of the report and a review of the nation's…

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies*

PubMed Central

Bolon, Brad; Barale-Thomas, Erio; Bradley, Alys; Ettlin, Robert A.; Franchi, Carla A.S.; George, Catherine; Giusti, Anna Maria; Hall, Robert; Jacobsen, Matthew; Konishi, Yoichi; Ledieu, David; Morton, Daniel; Park, Jae-Hak; Scudamore, Cheryl L.; Tsuda, Hiroyuki; Vijayasarathi, S.K.; Wijnands, Marcel V.W.

2010-01-01

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job “apprenticeship,” at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one’s understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. PMID:22272030

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

PubMed

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

2015-11-01

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

Toward Advancing Nano-Object Count Metrology: A Best Practice Framework

PubMed Central

Boyko, Volodymyr; Meyers, Greg; Voetz, Matthias; Wohlleben, Wendel

2013-01-01

Background: A movement among international agencies and policy makers to classify industrial materials by their number content of sub–100-nm particles could have broad implications for the development of sustainable nanotechnologies. Objectives: Here we highlight current particle size metrology challenges faced by the chemical industry due to these emerging number percent content thresholds, provide a suggested best-practice framework for nano-object identification, and identify research needs as a path forward. Discussion: Harmonized methods for identifying nanomaterials by size and count for many real-world samples do not currently exist. Although particle size remains the sole discriminating factor for classifying a material as “nano,” inconsistencies in size metrology will continue to confound policy and decision making. Moreover, there are concerns that the casting of a wide net with still-unproven metrology methods may stifle the development and judicious implementation of sustainable nanotechnologies. Based on the current state of the art, we propose a tiered approach for evaluating materials. To enable future risk-based refinements of these emerging definitions, we recommend that this framework also be considered in environmental and human health research involving the implications of nanomaterials. Conclusion: Substantial scientific scrutiny is needed in the area of nanomaterial metrology to establish best practices and to develop suitable methods before implementing definitions based solely on number percent nano-object content for regulatory purposes. Strong cooperation between industry, academia, and research institutions will be required to fully develop and implement detailed frameworks for nanomaterial identification with respect to emerging count-based metrics. Citation: Brown SC, Boyko V, Meyers G, Voetz M, Wohlleben W. 2013. Toward advancing nano-object count metrology: a best practice framework. Environ Health Perspect 121:1282–1291; http://dx.doi.org/10.1289/ehp.1306957 PMID:24076973

Strategic framework for education and training in Quality by Design (QbD) and process analytical technology (PAT).

PubMed

de Matas, Marcel; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, João Almeida; Oostra, Wim; Weimer, Marco; Öhrngren, Per; Rantanen, Jukka

2016-07-30

The regulatory and technical landscape of the pharmaceutical field is rapidly evolving from one focused predominantly on development of small molecules, using well established manufacturing technologies towards an environment in which biologicals and complex modalities are being developed using advanced science and technology coupled with the application of modern Quality by Design (QbD) principles. In order that Europe keeps pace with these changes and sustains its position as major player in the development and commercialization of medicines, it is essential that measures are put in place to maintain a highly skilled workforce. A number of challenges however exist to equipping academic, industrial and health agency staff with the requisite knowledge, skills and experience to develop the next generation of medicines. In this regard, the EUFEPS QbD and PAT Sciences Network has proposed a structured framework for education, training and continued professional development, which comprises a number of pillars covering the fundamental principles of modern pharmaceutical development including the underpinning aspects of science, engineering and technology innovation. The framework is not prescriptive and is not aimed at describing specific course content in detail. It should however be used as a point of reference for those institutions delivering pharmaceutical based educational courses, to ensure that the necessary skills, knowledge and experience for successful pharmaceutical development are maintained. A positive start has been made and a number of examples of formal higher education courses and short training programs containing elements of this framework have been described. The ultimate vision for this framework however, is to see widespread adoption and proliferation of this curriculum with it forming the backbone of QbD and PAT science based skills development. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of Coastal Governance for Climate Change Adaptation in Kenya

NASA Astrophysics Data System (ADS)

Ojwang, Lenice; Rosendo, Sergio; Celliers, Louis; Obura, David; Muiti, Anastasia; Kamula, James; Mwangi, Maina

2017-11-01

The coastline of Kenya already experiences effects of climate change, adding to existing pressures such as urbanization. Integrated coastal management (ICM) is increasingly recognized as a key policy response to deal with the multiple challenges facing coastal zones, including climate change. It can create an enabling governance environment for effective local action on climate change by facilitating a structured approach to dealing with coastal issues. It encompasses the actions of a wide range of actors, including local governments close to people and their activities affected by climate change. Functioning ICM also offers opportunities for reducing risks and building resilience. This article applied a modified capitals approach framework (CAF), consisting of five "capitals," to assess the status of county government capacity to respond to climate change within the context of coastal governance in three county governments in Kenya. The baseline was defined in terms of governance relating to the implementation of the interrelated policy systems of ICM and coastal climate change adaptation (CCA). The CAF framework provided a systematic approach to building a governance baseline against which to assess the progress of county governments in responding to climate change. It identified gaps in human capacity, financial resource allocation to adaptation and access to climate change information. Furthermore, it showed that having well-developed institutions, including regulatory frameworks at the national level can facilitate but does not automatically enable adaptation at the county level.

Glycoconjugate Vaccines: The Regulatory Framework.

PubMed

Jones, Christopher

2015-01-01

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

Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

PubMed

Dahm, Matthias; González, Paula; Porteiro, Nicolás

2009-12-01

Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

Nanotherapeutics--product development along the "nanomaterial" discussion.

PubMed

Wacker, Matthias G

2014-03-01

Nanomaterials have become part of formulation development in the pharmaceutical industry and offer exciting opportunities in the area of targeted drug delivery. But they may also exert unexpected toxicities and potentially pose a threat to human health and the environment. Since the Scientific Committee on Emerging and Newly Identified Health Risks recommended a definition of "nanomaterials" for implementation into the existing and upcoming regulatory framework in the European Union, a discussion about safety requirements of new nanoscale products has emerged. At the same time, the Food and Drug Administration of the United States still observes recent developments in this area. Although the impact on the pharmaceutical product chain is still uncertain, guidelines on risk assessment in food products and cosmetics are available and offer a preview of future developments in the regimens of pharmaceuticals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

PubMed

Grant, Evita V

Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

Natural Gas and the Transformation of the U.S. Energy Sector: Electricity

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

Logan, J.; Heath, G.; Macknick, J.

The Joint Institute for Strategic Energy Analysis (JISEA) designed this study to address four related key questions, which are a subset of the wider dialogue on natural gas: 1. What are the life cycle greenhouse gas (GHG) emissions associated with shale gas compared to conventional natural gas and other fuels used to generate electricity?; 2. What are the existing legal and regulatory frameworks governing unconventional gas development at federal, state, and local levels, and how are they changing in response to the rapid industry growth and public concerns?; 3. How are natural gas production companies changing their water-related practices?; andmore » 4. How might demand for natural gas in the electric sector respond to a variety of policy and technology developments over the next 20 to 40 years?« less

Interpretation of ALARA in the Canadian regulatory framework

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

Utting, R.

1995-03-01

The Atomic Energy Control Board (AECB) is responsible for the regulation of all aspects of atomic energy in Canada. This includes the complete nuclear fuel cycle from uranium mining to long-term disposal of nuclear fuel, as well as the medical and industrial utilization of radioisotopes. Clearly, the regulatory approach will differ from practice to practice but, as far as possible, the AECB has attempted to minimize the degree of prescription of regulatory requirements. The traditional modus operandi of the AECB has been to have broad general principles enshrined in regulations with the requirement that licensees submit specific operating policies andmore » procedures to the AECB for approval. In the large nuclear facilities with their sophisticated technical infrastructures, this policy has been largely successful although in a changing legal and political milieu the AECB is finding that a greater degree of proactive regulation is becoming necessary. With the smaller users, the AECB has for a long time found it necessary to have a greater degree of prescription in its regulatory function. Forthcoming General Amendments to the Atomic Energy Control Regulations will, amongst other things, formally incorporate the concept of ALARA into the Canadian regulatory framework. Within the broad range of practices licensed by the AECB it is not practical to provide detailed guidance on optimization that will be relevant and appropriate to all licensees, however the following general principles are proposed.« less

The "shoulds" and "should nots" of moral emotions: a self-regulatory perspective on shame and guilt.

PubMed

Sheikh, Sana; Janoff-Bulman, Ronnie

2010-02-01

A self-regulatory framework for distinguishing between shame and guilt was tested in three studies. Recently, two forms of moral regulation based on approach versus avoidance motivation have been proposed in the literature. Proscriptive regulation is sensitive to negative outcomes, inhibition based, and focused on what we should not do. Prescriptive regulation is sensitive to positive outcomes, activation based, and focused on what we should do. In the current research, consistent support was found for shame's proscriptive and guilt's prescriptive moral underpinnings. Study 1 found a positive association between avoidance orientation and shame proneness and between approach orientation and guilt proneness. In Study 2, priming a proscriptive orientation increased shame and priming a prescriptive orientation increased guilt. In Study 3, transgressions most apt to represent proscriptive and prescriptive violations predicted subsequent judgments of shame and guilt, respectively. This self-regulatory perspective provides a broad interpretive framework for understanding and extending past research findings.

The pluralization of the international: Resistance and alter-standardization in regenerative stem cell medicine

PubMed Central

Rosemann, Achim; Chaisinthop, Nattaka

2016-01-01

The article explores the formation of an international politics of resistance and ‘alter-standardization’ in regenerative stem cell medicine. The absence of internationally harmonized regulatory frameworks in the clinical stem cell field and the presence of lucrative business opportunities have resulted in the formation of transnational networks adopting alternative research standards and practices. These oppose, as a universal global standard, strict evidence-based medicine clinical research protocols as defined by scientists and regulatory agencies in highly developed countries. The emergence of transnational spaces of alter-standardization is closely linked to scientific advances in rapidly developing countries such as China and India, but calls for more flexible regulatory frameworks, and the legitimization of experimental for-profit applications outside of evidence-based medical care, are emerging increasingly also within more stringently regulated countries, such as the United States and countries in the European Union. We can observe, then, a trend toward the pluralization of the standards, practices, and concepts in the stem cell field. PMID:26983174

Toward a Safety Risk-Based Classification of Unmanned Aircraft

NASA Technical Reports Server (NTRS)

Torres-Pomales, Wilfredo

2016-01-01

There is a trend of growing interest and demand for greater access of unmanned aircraft (UA) to the National Airspace System (NAS) as the ongoing development of UA technology has created the potential for significant economic benefits. However, the lack of a comprehensive and efficient UA regulatory framework has constrained the number and kinds of UA operations that can be performed. This report presents initial results of a study aimed at defining a safety-risk-based UA classification as a plausible basis for a regulatory framework for UA operating in the NAS. Much of the study up to this point has been at a conceptual high level. The report includes a survey of contextual topics, analysis of safety risk considerations, and initial recommendations for a risk-based approach to safe UA operations in the NAS. The next phase of the study will develop and leverage deeper clarity and insight into practical engineering and regulatory considerations for ensuring that UA operations have an acceptable level of safety.

Markov State Models of gene regulatory networks.

PubMed

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

2017-02-06

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

77 FR 12898 - Self-Regulatory Organizations; Midwest Securities Trust Company; Order Cancelling Clearing Agency...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... the event any self-regulatory organization is no longer in existence or has ceased to do business in... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66461; File No. 600-7] Self-Regulatory Organizations; Midwest Securities Trust Company; Order Cancelling Clearing Agency Registration February 24, 2012...

77 FR 12896 - Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... Act provides that in the event any self- regulatory organization is no longer in existence or has... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66458; File No. 600-9] Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency Registration February 24, 2012. I...

78 FR 36278 - Fuel Oil Systems for Emergency Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

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

Mapping regulatory models for medicinal cannabis: a matrix of options.

PubMed

Belackova, Vendula; Shanahan, Marian; Ritter, Alison

2017-05-30

Objective The aim of the present study was to develop a framework for assessing regulatory options for medicinal cannabis in Australia. Methods International regulatory regimes for medicinal cannabis were reviewed with a qualitative policy analysis approach and key policy features were synthesised, leading to a conceptual framework that facilitates decision making across multiple dimensions. Results Two central organising dimensions of medicinal cannabis regulation were identified: cannabis supply and patient authorisation (including patient access). A number of the different supply options can be matched with a number of different patient authorisation options, leading to a matrix of possible regulatory regimes. Conclusions The regulatory options, as used internationally, involve different forms of cannabis (synthetic and plant-based pharmaceutical preparations or herbal cannabis) and the varying extent to which patient authorisation policies and procedures are stringently or more loosely defined. The optimal combination of supply and patient authorisation options in any jurisdiction that chooses to make medicinal cannabis accessible will depend on policy goals. What is known about the topic? Internationally, regulation of medicinal cannabis has developed idiosyncratically, depending on formulations that were made available and local context. There has been no attempt to date in the scientific literature to systematically document the variety of regulatory possibilities for medicinal cannabis. What does this paper add? This paper presents a new conceptual schema for considering options for the regulation of medicinal cannabis, across both supply and patient authorisation aspects. What are the implications for practitioners? The design of regulatory systems in Australia, whether for pharmaceutical or herbal products, is a vital issue for policy makers right now as federal and state and territory governments grapple with the complexities of medicinal cannabis regulation. The conceptual schema presented herein provides a tool for more systematic thinking about the options.

Risky business.

PubMed

Baram, M

1996-10-01

In prior studies by high-level commissions, emphasis was given to improving the scientific basis and institutional procedures for risk assessment and risk regulation within existing statutory frameworks. Recommendations have led to slow but steady progress. This study is considerably different. It emphasizes a public health approach for efficient use of resources in a new flexible framework for risk management, reductionist approaches to risk assessment and characterization, increased public involvement, and various methods for managing such public involvement. It provides a mix of aspirations and concepts, procedures, and "shop floor rules" for putting the new system of risk management into practice. Concerns remain, however, that bright lines and other rules are at odds with the report's professed aspirations for meaningful public involvement; that ad hoc institutional arrangements for putting each risk in a situational context may not be an efficient use of public and private resources; that techniques for managing stakeholder involvement will be seen as manipulative and may even increase public mistrust and anxieties about risk; and that reductionism by the regulatory clients of risk assessment could diminish progress in the environmental health sciences. Says Lucier, "The goal of risk assessment should be to prevent environmentally or occupationally mediated diseases or injury. This point is not made sufficiently clear in the commission's report. Nevertheless, the report does an admirable job of attempting to merge science, common sense, public perception, public health, economics, and stakeholder interests into a regulatory policy strategy." He continues, "The merging of these diverse inputs will never be easy and should never be overly prescriptive. The complete integration of all relevant information into the risk assessment and risk management process will require greater reliance on expert judgment to make decisions that are timely, that are based on appropriate peer review, that are consistent with public health priorities, that do not create unnecessary regulatory burdens, and that are understandable by the public." The commission's report provides an alternative vision of risk management that incorporates popular political and social trends. Thorough evaluation of the report's recommendations will, at the very least, focus scrutiny on current risk assessment and risk management practices and perhaps produce better solutions.

Risky business.

PubMed Central

Baram, M

1996-01-01

In prior studies by high-level commissions, emphasis was given to improving the scientific basis and institutional procedures for risk assessment and risk regulation within existing statutory frameworks. Recommendations have led to slow but steady progress. This study is considerably different. It emphasizes a public health approach for efficient use of resources in a new flexible framework for risk management, reductionist approaches to risk assessment and characterization, increased public involvement, and various methods for managing such public involvement. It provides a mix of aspirations and concepts, procedures, and "shop floor rules" for putting the new system of risk management into practice. Concerns remain, however, that bright lines and other rules are at odds with the report's professed aspirations for meaningful public involvement; that ad hoc institutional arrangements for putting each risk in a situational context may not be an efficient use of public and private resources; that techniques for managing stakeholder involvement will be seen as manipulative and may even increase public mistrust and anxieties about risk; and that reductionism by the regulatory clients of risk assessment could diminish progress in the environmental health sciences. Says Lucier, "The goal of risk assessment should be to prevent environmentally or occupationally mediated diseases or injury. This point is not made sufficiently clear in the commission's report. Nevertheless, the report does an admirable job of attempting to merge science, common sense, public perception, public health, economics, and stakeholder interests into a regulatory policy strategy." He continues, "The merging of these diverse inputs will never be easy and should never be overly prescriptive. The complete integration of all relevant information into the risk assessment and risk management process will require greater reliance on expert judgment to make decisions that are timely, that are based on appropriate peer review, that are consistent with public health priorities, that do not create unnecessary regulatory burdens, and that are understandable by the public." The commission's report provides an alternative vision of risk management that incorporates popular political and social trends. Thorough evaluation of the report's recommendations will, at the very least, focus scrutiny on current risk assessment and risk management practices and perhaps produce better solutions. PMID:8930543

Bridging the gap between regulatory acceptance and industry use of non-animal methods.

PubMed

Clippinger, Amy J; Hill, Erin; Curren, Rodger; Bishop, Patricia

2016-01-01

Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case-by-case basis, to conventional pesticide products. Despite the collaborative effort, the availability of relevant non-animal methods, and the EPA's change in policy, only a limited number of AMCPs have been registered using the framework. Companies continue to conduct animal tests when registering AMCPs due to various challenges surrounding adoption of the new testing framework; however, recent discussions between industry, regulators, and other interested parties have identified ways these challenges may be overcome. In this article we explore how use of the alternate framework could be expanded through efforts such as increasing international harmonization, more proactively publicizing the framework, and enhancing the training of regulatory reviewers. Not only can these strategies help to increase use of the EPA alternate eye irritation framework, they can also be applied to facilitate the uptake of other alternative approaches to animal testing in the future.

In Silico Evaluation of the Impacts of Quorum Sensing Inhibition (QSI) on Strain Competition and Development of QSI Resistance

NASA Astrophysics Data System (ADS)

Wei, Guopeng; Lo, Chieh; Walsh, Connor; Hiller, N. Luisa; Marculescu, Radu

2016-10-01

As understanding of bacterial regulatory systems and pathogenesis continues to increase, QSI has been a major focus of research. However, recent studies have shown that mechanisms of resistance to quorum sensing (QS) inhibitors (QSIs) exist, calling into question their clinical value. We propose a computational framework that considers bacteria genotypes relative to QS genes and QS-regulated products including private, quasi-public, and public goods according to their impacts on bacterial fitness. Our results show (1) QSI resistance spreads when QS positively regulates the expression of private or quasi-public goods. (2) Resistance to drugs targeting secreted compounds downstream of QS for a mix of private, public, and quasi-public goods also spreads. (3) Changing the micro-environment during treatment with QSIs may decrease the spread of resistance. At fundamental-level, our simulation framework allows us to directly quantify cell-cell interactions and biofilm dynamics. Practically, the model provides a valuable tool for the study of QSI-based therapies, and the simulations reveal experimental paths that may guide QSI-based therapies in a manner that avoids or decreases the spread of QSI resistance.

Midwifery participatory curriculum development: Transformation through active partnership.

PubMed

Sidebotham, Mary; Walters, Caroline; Chipperfield, Janine; Gamble, Jenny

2017-07-01

Evolving knowledge and professional practice combined with advances in pedagogy and learning technology create challenges for accredited professional programs. Internationally a sparsity of literature exists around curriculum development for professional programs responsive to regulatory and societal drivers. This paper evaluates a participatory curriculum development framework, adapted from the community development sector, to determine its applicability to promote engagement and ownership during the development of a Bachelor of Midwifery curriculum at an Australian University. The structures, processes and resulting curriculum development framework are described. A representative sample of key curriculum development team members were interviewed in relation to their participation. Qualitative analysis of transcribed interviews occurred through inductive, essentialist thematic analysis. Two main themes emerged: (1) 'it is a transformative journey' and (2) focused 'partnership in action'. Results confirmed the participatory curriculum development process provides symbiotic benefits to participants leading to individual and organisational growth and the perception of a shared curriculum. A final operational model using a participatory curriculum development process to guide the development of accredited health programs emerged. The model provides an appropriate structure to create meaningful collaboration with multiple stakeholders to produce a curriculum that is contemporary, underpinned by evidence and reflective of 'real world' practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

A statistical image analysis framework for pore-free islands derived from heterogeneity distribution of nuclear pore complexes.

PubMed

Mimura, Yasuhiro; Takemoto, Satoko; Tachibana, Taro; Ogawa, Yutaka; Nishimura, Masaomi; Yokota, Hideo; Imamoto, Naoko

2017-11-24

Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate NPC assembly in interphase, the location of NPC assembly on the nuclear envelope is not clear. CDKs also regulate the disappearance of pore-free islands, which are nuclear envelope subdomains; this subdomain gradually disappears with increase in homogeneity of the NPC in response to CDK activity. However, a causal relationship between pore-free islands and NPC assembly remains unclear. Here, we elucidated mechanisms underlying NPC assembly from a new perspective by focusing on pore-free islands. We proposed a novel framework for image-based analysis to automatically determine the detailed 'landscape' of pore-free islands from a large quantity of images, leading to the identification of NPC intermediates that appear in pore-free islands with increased frequency in response to CDK activity. Comparison of the spatial distribution between simulated and the observed NPC intermediates within pore-free islands showed that their distribution was spatially biased. These results suggested that the disappearance of pore-free islands is highly related to de novo NPC assembly and indicated the existence of specific regulatory mechanisms for the spatial arrangement of NPC assembly on nuclear envelopes.

A framework to analyze emissions implications of manufacturing shifts in the industrial sector through integrating bottom-up energy models and economic input/output environmental life cycle assessment models

EPA Science Inventory

Future year emissions depend highly on economic, technological, societal and regulatory drivers. A scenario framework was adopted to analyze technology development pathways and changes in consumer preferences, and evaluate resulting emissions growth patterns while considering fut...

76 FR 25274 - Reopening and Extension of Comment Periods for Rulemakings Implementing the Dodd-Frank Wall...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... establish a comprehensive new framework for the regulation of swaps. In order to provide interested parties... proposed new regulatory framework, the Commission is reopening or extending the comment period for many of its proposed rulemakings. The Commission is also requesting comment on the order in which it should...

Carousel: A Moral Framework for Inquiring into the Culture of Prisons and Academe.

ERIC Educational Resources Information Center

Mullen, Carol A.

The moral framework of a carousel is used to advance possible connections between the institutional and regulatory life within prisons and teacher education programs. The moral paradigm case narrated is based on the researcher's field experience in a prison as a researcher-teacher. Connections are drawn to restrictions within a correctional…

Which lessons can we learn from the European Union legal framework of medicines for the regulation of direct-to-consumer genetic tests?

PubMed

van Hellemondt, Rachèl; Hendriks, Aart; Breuning, Martijn

2012-01-01

The legal framework of the European Union (EU) for regulating access to and supply of direct-to-consumer (DTC) genetic tests is very liberal compared to the legal and regulatory framework for (internet) medicines. Nevertheless, both health related products can cause equally serious damage to the well being of individuals. In this contribution we examine whether the legal framework of the EU for the safety and responsible use of (internet) medicines could be an example for regulating access to and supply of DTC genetic tests. The EU laws governing medicines can, notwithstanding their shortcomings, serve as an example for (central) authorising the marketing of DTC genetic tests on the internal market in accordance with strict criteria regarding predictive value and clinical usefulness. Furthermore, a legal framework controlling DTC genetic tests also should introduce system supervision as well as quality criteria with respect to the information to be provided to consumers in order to enhance health protection. However, DTC genetic tests purchased through online ordering are difficult to supervise by any agency. Adequately protecting individuals against questionable testing kits calls for international vigilance and comprehensive measures by the international community. For Europe, it is important to rank the regulation of DTC genetic tests on the European regulatory agenda.

An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.

PubMed

Wang, Zi; Ramsey, Benjamin J; Wang, Dali; Wong, Kwai; Li, Husheng; Wang, Eric; Bao, Zhirong

2016-01-01

With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact in vivo to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study C. elegans embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations.

Evaluating the effectiveness of risk minimisation measures: the application of a conceptual framework to Danish real-world dabigatran data.

PubMed

Nyeland, Martin Erik; Laursen, Mona Vestergaard; Callréus, Torbjörn

2017-06-01

For both marketing authorization holders and regulatory authorities, evaluating the effectiveness of risk minimization measures is now an integral part of pharmacovigilance in the European Union. The overall aim of activities in this area is to assess the performance of risk minimization measures implemented in order to ensure a positive benefit-risk balance in patients treated with a medicinal product. Following a review of the relevant literature, we developed a conceptual framework consisting of four domains (data, knowledge, behaviour and outcomes) intended for the evaluation of risk minimization measures put into practice in the Danish health-care system. For the implementation of the framework, four classes of monitoring variables can be named and defined: patient descriptors, performance-related indicators of knowledge, behaviour and outcomes. We reviewed the features of the framework when applied to historical, real-world data following the introduction of dabigatran in Denmark for the prophylactic treatment of patients with non-valvular atrial fibrillation. The application of the framework provided useful graphical displays and an opportunity for a statistical evaluation (interrupted time series analysis) of a regulatory intervention. © 2017 Commonwealth of Australia. Pharmacoepidemiology & Drug Safety © 2017 John Wiley & Sons, Ltd. © 2017 Commonwealth of Australia. Pharmacoepidemiology & Drug Safety © 2017 John Wiley & Sons, Ltd.

An Ethical Framework for Evaluating Experimental Technology.

PubMed

van de Poel, Ibo

2016-06-01

How are we to appraise new technological developments that may bring revolutionary social changes? Currently this is often done by trying to predict or anticipate social consequences and to use these as a basis for moral and regulatory appraisal. Such an approach can, however, not deal with the uncertainties and unknowns that are inherent in social changes induced by technological development. An alternative approach is proposed that conceives of the introduction of new technologies into society as a social experiment. An ethical framework for the acceptability of such experiments is developed based on the bioethical principles for experiments with human subjects: non-maleficence, beneficence, respect for autonomy, and justice. This provides a handle for the moral and regulatory assessment of new technologies and their impact on society.

[Enforceability of the right to health protection in obstetric services in Mexico].

PubMed

Meza, Alejandro; Mancinas, Sandra; Meneses, Sergio; Meléndez, David

2015-05-01

The inclusion of the framework of human rights in maternal health is mentioned more and more frequently as a feasible proposal to improve the care that women receive in obstetric health care services. Despite the fact Mexico has a solid regulatory framework for obstetric care, mechanisms of enforceability are essential to ensure that health-related human rights are upheld. In addition to being in place, enforceability mechanisms should be effective and accessible to people, particularly in obstetric care, where repeated human rights violations occur that endanger women's health and lives. The objective of this article is to specify the regulatory, legal, and extralegal elements that need to be considered in order to include maternal health in a set of enforceable human rights.

Towards a better pesticide policy for the European Union.

PubMed

Storck, Veronika; Karpouzas, Dimitrios G; Martin-Laurent, Fabrice

2017-01-01

This opinion article aims to foster the debate about pesticide legislation in the European Union (EU). Numerous formerly authorized and widely used pesticides are now banned in the EU because unexpected and unacceptable risks emerged after their initial introduction to the market. Throughout this time lapse, environmental quality and human health have been threatened by the use of these compounds. These hazards could have been prevented by a more responsive pesticide regulatory framework. This article provides detailed insights into the pros and cons of pesticides, and points out weaknesses of the current pesticide environmental risk assessment procedures. Possibilities for improving the robustness and reliability of the pesticide regulatory framework are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancements Needed in GE Crop and Food Regulation in the U.S.

PubMed Central

Benbrook, Charles

2016-01-01

Genetically engineered (GE) crops, multi-ingredient foods derived from one or more GE ingredients, and GE agricultural inputs are regulated in the United States under a “Coordinated Framework” that was literally cobbled together in the early 1990s. Via this Framework, responsibility is spread across three federal agencies for the assessment and management of potential risks arising from the planting of GE crops, the raising of GE animals, or uses of GE inputs. The Framework was incomplete and conceptually flawed from the beginning. Despite multiple, piecemeal efforts to update aspects of GE risk assessment and regulatory policy, the Coordinated Framework survives to this day largely unchanged. Its shortcomings are recognized in both the scientific and legal communities, but meaningful reforms thus far remain out of reach, blocked by the intense controversy now surrounding all things biotech. Five generic reforms and another five specific initiatives are described to create a more robust, science-driven GE regulatory infrastructure in the U.S. PMID:27066473

Interpersonal emotion regulation.

PubMed

Zaki, Jamil; Williams, W Craig

2013-10-01

Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

CAAT Altex workshop paper entitled "Towards Good Read ...

EPA Pesticide Factsheets

Grouping of substances and utilizing read-across within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity, and increasingly often, also on mechanistic similarity. While read-across can play a key role in complying with legislations such as the European REACH legislation, the lack of consensus regarding the extent and type of evidence necessary to support it often hampers it’s successful application and acceptance by regulatory authorities. Despite a potentially broad user community, expertise is still concentrated across a handful of organizations and individuals. In order to facilitate the effective use of read-across, this document aims to summarize the state-of-the-art, summarise insights learned from reviewing ECHA published decisions as far as the relative successes/pitfalls surrounding read-across under the REACH and compile the relevant activities and guidance documents. Special emphasis is given to the available existing tools and approaches, the consideration and expression of uncertainty, the use of biological support data and the potential impact of the ECHA Read-Across Assessment Framework (RAAF) which was published in 2015. This is a paper that summarises different activities and research needs for read-across for regulatory purposes that has been compiled as a result of a CAAT initiative led by Thomas Hartung.

One step forward, two steps back: worker representation and health and safety in the United Kingdom.

PubMed

Walters, David

2006-01-01

There is now quite strong evidence for a set of preconditions that help determine the effectiveness of worker representation and consultation in improving health and safety outcomes. One of these preconditions is a regulatory framework that defines workers' rights to representation and employers' obligations to respond. Using the United Kingdom as its focus, this article explores developments at the national policy level. It shows how long-awaited legislative reforms to improve provisions for worker representation in health and safety have so far failed to materialize and, instead, government strategy has concentrated on promoting voluntary approaches. The author reviews the evidence of what makes worker representation in health and safety effective and suggests that, far from abandoning approaches to legislative reform, the U.K. agencies should be seeking to make improvements to the British provisions if they are to provide the necessary stimulus and support for worker representation in health and safety at work. Such improvements need to address long-standing weaknesses in existing provisions and their relevance to the changing world of work. The arguments presented here apply to the essential role of regulatory support for worker participation in all advanced market economies if it is to improve health and safety outcomes.

Positive beliefs about rumination are associated with ruminative thinking and affect in daily life: evidence for a metacognitive view on depression.

PubMed

Kubiak, Thomas; Zahn, Daniela; Siewert, Kerstin; Jonas, Cornelia; Weber, Hannelore

2014-09-01

Self-regulatory executive function theory (Wells and Matthews, 1994; Wells, 2008) stresses the role of metacognitions in the development of emotional disorders. Within this metacognitive model, positive beliefs about ruminative thinking are thought to be a risk factor for engaging in rumination and subsequently for depression. However, most of the existing research relies on retrospective self-report trait measures. The aim of the present study was to examine the theory's predictions with an Ecological Momentary Assessment approach capturing rumination as it occurs in daily life. Non-clinical participants (N = 93) were equipped with electronic diaries and completed four signal-contingent momentary self-reports per day for 4 weeks. A multilevel mediation model was computed to examine associations between positive beliefs about rumination and ruminative thinking and negative affect in daily life. Positive beliefs about rumination were significantly associated with ruminative thinking as it occurs in daily life. We further found evidence for a negative association with positive affect that was completely mediated via ruminative thinking in daily life occurring in response to negative emotions. Our results add ecologically valid corroborating evidence for the metacognitive model of emotional disorders within the framework of self-regulatory executive function theory.

Regulating small things: genes, gametes and nanotechnology.

PubMed

Bennett, Belinda

2007-08-01

Biotechnology and nanotechnology both intersect with other technologies in ways that open new possibilities for further technological progress. The potential for increased convergence between technological fields highlights the need for regulatory frameworks to be integrated, flexible and responsive. Within a federal legal system such as Australia's, there is a need to ensure that we adopt a coordinated national approach to the crafting of regulatory solutions. In addition, there is a need for global cooperation in the development of international standards and regulatory harmonisation. Finally, this article considers the role that law plays in negotiating risk in relation to new technologies.

A model for communication skills assessment across the undergraduate curriculum.

PubMed

Rider, Elizabeth A; Hinrichs, Margaret M; Lown, Beth A

2006-08-01

Physicians' interpersonal and communication skills have a significant impact on patient care and correlate with improved healthcare outcomes. Some studies suggest, however, that communication skills decline during the four years of medical school. Regulatory and other medical organizations, recognizing the importance of interpersonal and communication skills in the practice of medicine, now require competence in communication skills. Two challenges exist: to select a framework of interpersonal and communication skills to teach across undergraduate medical education, and to develop and implement a uniform model for the assessment of these skills. The authors describe a process and model for developing and institutionalizing the assessment of communication skills across the undergraduate curriculum. Consensus was built regarding communication skill competencies by working with course leaders and examination directors, a uniform framework of competencies was selected to both teach and assess communication skills, and the framework was implemented across the Harvard Medical School undergraduate curriculum. The authors adapted an assessment framework based on the Bayer-Fetzer Kalamazoo Consensus Statement adapted a patient and added and satisfaction tool to bring patients' perspectives into the assessment of the learners. The core communication competencies and evaluation instruments were implemented in school-wide courses and assessment exercises including the first-year Patient-Doctor I Clinical Assessment, second-year Objective Structured Clinical Exam (OSCE), third-year Patient-Doctor III Clinical Assessment, fourth-year Comprehensive Clinical Practice Examination and the Core Medicine Clerkships. Faculty were offered workshops and interactive web-based teaching to become familiar with the framework, and students used the framework with repeated opportunities for faculty feedback on these skills. A model is offered for educational leaders and others who are involved in designing assessment in communication skills. By presenting an approach for implementation, the authors hope to provide guidance for the successful integration of communication skills assessment in undergraduate medical education.

Current regulatory issues in cell and tissue therapy.

PubMed

Burger, S R

2003-01-01

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

The Normative Structure of Knowledge Production and Utilization in Education: A Report on Work in Progress.

ERIC Educational Resources Information Center

Markley, O. W.

The primary objective of this study is to develop a systems-oriented analytical framework with which to better understand how formal policies serve as regulatory influences on knowledge production and utilization (KPU) in education. When completed, the framework being developed should be able to organize information about the KPU system and its…

Utilising Enterprise Risk Management Strategies to Develop a Governance and Operations Framework for a New Research Complex: A Case Study

ERIC Educational Resources Information Center

Clyde-Smith, Jodi

2014-01-01

Enterprise risk management strategies were used to develop a regulatory and operational framework for a new multi-partner Research Institute that will house up to 900 staff from four different institutions in Queensland, Australia. The Institute will operate in a business environment while functioning as a research resource for the higher…

Transatlantic Regulatory Cooperation: Background and Analysis

DTIC Science & Technology

2008-10-22

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

[Regulatory Framework for Approval of PET Drug in Korea: A Survey Report].

PubMed

Kurihara, Chieko; Inoue, Tomio

2015-11-01

To identify regulatory framework for approval of PET drugs in Korea. Interview and literature survey. In Korea Good Manufacturing Practice (GMP) regulation specific to radiopharmaceuticals, including PET (Positron Emission Tomography) drugs, under the Pharmaceutical Affairs Act was issued in August 2014, to be enforced on July 1, 2015, and its guidance was issued in December 2014. The new facilities to be established after July 1 of 2015 have to be compatible with this new regulation and already established facilities have two years grace period until June 30 of 2017. During this period, the regulatory authority will inspect all of the production sites which hold or submit approvals of radiopharmaceuticals. As of September 2015 in Korea, there are 7 commercial companies and 15 hospitals and institutes, which have approvals of PET drugs mainly FDG, and these companies and/or hospitals can supply PET drugs outside institutions. In this article we introduce the Korean regulations of development and approval of radiopharmaceuticals. The Korean regulatory authorization policy for radiopharmaceuticals are to some extent similar to the policy which the U.S. regulators set as the new regulations of PET drug. It is expected that the situations of production sites in Korea are to be improved through actual discussions among regulators and PET community through the process of actual inspection.

Work-related stress risk assessment in Italy: a methodological proposal adapted to regulatory guidelines.

PubMed

Persechino, Benedetta; Valenti, Antonio; Ronchetti, Matteo; Rondinone, Bruna Maria; Di Tecco, Cristina; Vitali, Sara; Iavicoli, Sergio

2013-06-01

Work-related stress is one of the major causes of occupational ill health. In line with the regulatory framework on occupational health and safety (OSH), adequate models for assessing and managing risk need to be identified so as to minimize the impact of this stress not only on workers' health, but also on productivity. After close analysis of the Italian and European reference regulatory framework and work-related stress assessment and management models used in some European countries, we adopted the UK Health and Safety Executive's (HSE) Management Standards (MS) approach, adapting it to the Italian context in order to provide a suitable methodological proposal for Italy. We have developed a work-related stress risk assessment strategy, meeting regulatory requirements, now available on a specific web platform that includes software, tutorials, and other tools to assist companies in their assessments. This methodological proposal is new on the Italian work-related stress risk assessment scene. Besides providing an evaluation approach using scientifically validated instruments, it ensures the active participation of occupational health professionals in each company. The assessment tools provided enable companies not only to comply with the law, but also to contribute to a database for monitoring and assessment and give access to a reserved area for data analysis and comparisons.

Work-Related Stress Risk Assessment in Italy: A Methodological Proposal Adapted to Regulatory Guidelines

PubMed Central

Persechino, Benedetta; Valenti, Antonio; Ronchetti, Matteo; Rondinone, Bruna Maria; Di Tecco, Cristina; Vitali, Sara; Iavicoli, Sergio

2013-01-01

Background Work-related stress is one of the major causes of occupational ill health. In line with the regulatory framework on occupational health and safety (OSH), adequate models for assessing and managing risk need to be identified so as to minimize the impact of this stress not only on workers' health, but also on productivity. Methods After close analysis of the Italian and European reference regulatory framework and work-related stress assessment and management models used in some European countries, we adopted the UK Health and Safety Executive's (HSE) Management Standards (MS) approach, adapting it to the Italian context in order to provide a suitable methodological proposal for Italy. Results We have developed a work-related stress risk assessment strategy, meeting regulatory requirements, now available on a specific web platform that includes software, tutorials, and other tools to assist companies in their assessments. Conclusion This methodological proposal is new on the Italian work-related stress risk assessment scene. Besides providing an evaluation approach using scientifically validated instruments, it ensures the active participation of occupational health professionals in each company. The assessment tools provided enable companies not only to comply with the law, but also to contribute to a database for monitoring and assessment and give access to a reserved area for data analysis and comparisons. PMID:23961332

A Critical Analysis of Purchasing Arrangements in Kenya: The Case of the National Hospital Insurance Fund

PubMed Central

Munge, Kenneth; Mulupi, Stephen; Barasa, Edwine W.; Chuma, Jane

2018-01-01

Background: Purchasing refers to the process by which pooled funds are paid to providers in order to deliver a set of health care interventions. Very little is known about purchasing arrangements in low- and middle-income countries (LMICs), and certainly not in Kenya. This study aimed to critically analyse purchasing arrangements in Kenya, using the National Hospital Insurance Fund (NHIF) as a case study. Methods: We applied a principal-agent relationship framework, which identifies three pairs of principal-agent relationships (government-purchaser, purchaser-provider, and citizen-purchaser) and specific actions required within them to achieve strategic purchasing. A qualitative case study approach was applied. Data were collected through document reviews (statutes, policy and regulatory documents) and in-depth interviews (n=62) with key informants including NHIF officials, Ministry of Health (MoH) officials, insurance industry actors, and health service providers. Documents were summarised using standardised forms. Interviews were recorded, transcribed verbatim, and analysed using a thematic framework approach. Results: The regulatory and policy framework for strategic purchasing in Kenya was weak and there was no clear accountability mechanism between the NHIF and the MoH. Accountability mechanisms within the NHIF have developed over time, but these emphasized financial performance over other aspects of purchasing. The processes for contracting, monitoring, and paying providers do not promote equity, quality, and efficiency. This was partly due to geographical distribution of providers, but also due to limited capacity within the NHIF. There are some mechanisms for assessing needs, preferences, and values to inform design of the benefit package, and while channels to engage beneficiaries exist, they do not always function appropriately and awareness of these channels to the beneficiaries is limited. Conclusion: Addressing the gaps in the NHIF’s purchasing performance requires a number of approaches. Critically, there is a need for the government through the MoH to embrace its stewardship role in health, while recognizing the multiplicity of actors given Kenya’s devolved context. Relatively recent decentralisation reforms present an opportunity that should be grasped to rewrite the contract between the government, the NHIF and Kenyans in the pursuit of universal health coverage (UHC). PMID:29524953

Reasserting the primacy of human needs to reclaim the 'lost half' of sustainable development.

PubMed

Everard, Mark; Longhurst, James W S

2018-04-15

The concept of sustainable development evolved from growing awareness of the interdependence of social and economic progress with the limits of the supporting natural environment, becoming progressively integrated into global agreements and transposition into local regulatory and implementation frameworks. We argue that transposition of the concept into regulation and supporting tools reduced the focus to minimal environmental and social standards, perceived as imposing constraints rather than opportunities for innovation to meet human needs. The aspirational 'half' of the concept of sustainable development specifically addressing human needs was thus lost in transposing high ideals into regulatory instruments. The Sustainable Development Goals (SDGs) restore focus on interlinked human needs, stimulating innovation of products and processes to satisfy them. Through three case studies - PVC water pipes, river quality management in England, and UK local air quality management - we explore the current operationalisation of the concept in diverse settings, using the SDG framework to highlight the broader societal purposes central to sustainable development. Partnerships involving civil society support evolution of regulatory instruments and their implementation, optimising social and ecological benefits thereby serving more human needs. Restoring the visionary 'lost half' of sustainable development - meeting human needs in sustainable ways - creates incentives for innovation and partnership; an innovation framework rather than a perceived constraint. Copyright © 2017 Elsevier B.V. All rights reserved.

Opportunities and obstacles to the development of nanopharmaceuticals for human use.

PubMed

Nassiri Koopaei, Nasser; Abdollahi, Mohammad

2016-10-06

Pharmaceutical nanotechnology has generated breakthrough developments in improving health care and human life from its emergence. The biomaterials employed mainly aim at improving drug delivery systems, imaging and diagnostic technologies while the nanoscale materials are in widespread use in other industries such as electronics and optics. Such advancement may revolutionize the drug development and therapy with new and more efficient treatments. Although, nanotechnology assists humankind in improving its well being, it has certain limitations that entail thorough investigation by the regulatory and scientific authorities. To address concerns regarding the safety and toxicity profile of the nanopharmaceuticals, we have reviewed the challenges and solutions of nanopharmaceuticals use in human health and the related health risks. In this regard, regulatory and scientific bodies such as countries' Food and Drug Administration (FDA), Organization for Economic Co-operation and Development (OECD), European Medicine Agency (EMA), Environmental Protection Agency (EPA), National Institute for Occupational Safety and Health (NIOSH), and World Health Organization (WHO) can participate in developing and reinforcing safety measures and regulatory frameworks to insure the public health. The regulatory authorities may enforce the nanopharmaceutical industries to conduct comprehensive toxicity tests and monitor the adverse drug reaction reports in close collaboration with the scientific community to act accordingly and inform the public as the implementation of the strategy. Nanopharmaceuticals have tremendous potential for human use as therapeutic or diagnostic agents. But their toxicity profile should be well addressed and the respective regulatory framework developed and reinforced by the authorities.

CMIP: a software package capable of reconstructing genome-wide regulatory networks using gene expression data.

PubMed

Zheng, Guangyong; Xu, Yaochen; Zhang, Xiujun; Liu, Zhi-Ping; Wang, Zhuo; Chen, Luonan; Zhu, Xin-Guang

2016-12-23

A gene regulatory network (GRN) represents interactions of genes inside a cell or tissue, in which vertexes and edges stand for genes and their regulatory interactions respectively. Reconstruction of gene regulatory networks, in particular, genome-scale networks, is essential for comparative exploration of different species and mechanistic investigation of biological processes. Currently, most of network inference methods are computationally intensive, which are usually effective for small-scale tasks (e.g., networks with a few hundred genes), but are difficult to construct GRNs at genome-scale. Here, we present a software package for gene regulatory network reconstruction at a genomic level, in which gene interaction is measured by the conditional mutual information measurement using a parallel computing framework (so the package is named CMIP). The package is a greatly improved implementation of our previous PCA-CMI algorithm. In CMIP, we provide not only an automatic threshold determination method but also an effective parallel computing framework for network inference. Performance tests on benchmark datasets show that the accuracy of CMIP is comparable to most current network inference methods. Moreover, running tests on synthetic datasets demonstrate that CMIP can handle large datasets especially genome-wide datasets within an acceptable time period. In addition, successful application on a real genomic dataset confirms its practical applicability of the package. This new software package provides a powerful tool for genomic network reconstruction to biological community. The software can be accessed at http://www.picb.ac.cn/CMIP/ .

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

PubMed

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Lost in Translation? Ethical Challenges of Implementing a New Diagnostic Procedure.

PubMed

Schmitz, Dagmar

2016-01-01

Since cell-free DNA (cfDNA) fragments of placental origin can be isolated and analyzed from the blood of pregnant women. Applications of this finding have been developed and implemented in clinical care pathways worldwide at an unprecedented pace and manner. Implementation patterns, however, exhibit considerable insufficiencies. Different "motors" of implementation processes, like the market or various regulatory institutions, can be identified at a national level. Each "motor" entails characteristic ethical challenges which are exemplified impressively by a rising number of case reports.Empirical data demonstrate that there are significant "losses" in the respective translational processes, especially when the results from clinical research are to be translated into the clinical reality of NIPT (the so called "second roadblock" (T2)). These "losses" are perceived in the fields of knowledge transfer, professional standardization and ethical debate. Recommendations of professional organizations often fail to reach general practitioners. Blindsided by the new diagnostic procedure in their clinical practice, professionals in prenatal care express their insecurities with regard to its handling. Ethical debate appears to adhere to pre-existing (and partly already proven to be insufficient) normative frameworks for prenatal testing. While all of these deficits are typical for the implementation processes of many new molecular diagnostic procedures, especially in NIPT, they show a high variability between different nations.A critical assessment of the preferred strategy of implementation against the background of already existing national ethical frameworks is indispensable, if potential adverse effects are to be diminished. The described translational losses seem to be significantly reducible by granting the translational process in roadblock T2 more time.

Tabulation of asbestos-related terminology

USGS Publications Warehouse

Lowers, Heather; Meeker, Greg

2002-01-01

The term asbestos has been defined in numerous publications including many State and Federal regulations. The definition of asbestos often varies depending on the source or publication in which it is used. Differences in definitions also exist for the asbestos-related terms acicular, asbestiform, cleavage, cleavage fragment, fiber, fibril, fibrous, and parting. An inexperienced reader of the asbestos literature would have difficulty understanding these differences and grasping many of the subtleties that exist in the literature and regulatory language. Disagreement among workers from the industrial, medical, mineralogical, and regulatory communities regarding these definitions has fueled debate as to their applicability to various morphological structures and chemical compositions that exist in the amphibole and serpentine groups of minerals. This debate has significant public health, economic and legal implications. This report summarizes asbestos-related definitions taken from a variety of academic, industrial, and regulatory sources. This summary is by no means complete but includes the majority of significant definitions currently applied in the discipline.

Regulatory Approaches for Adding Capacity to Existing Hydropower Facilities

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

Levine, Aaron L.; Curtis, Taylor L.; Kazerooni, Borna

In 2015, hydroelectric generation accounted for more than 6 percent of total net electricity generation in the United States and 46 percent of electricity generation from all renewables. The United States has considerable hydroelectric potential beyond what is already being developed. Nearly 7 GW of this potential is found by adding capacity to existing hydropower facilities. To optimize the value of hydroelectric generation, the U.S. Department of Energy's Hydropower Vision Study highlights the importance of adding capacity to existing facilities. This report provides strategic approaches and considerations for Federal Energy Regulatory Commission licensed and exempt hydropower facilities seeking to increasemore » generation capacity, which may include increases from efficiency upgrades. The regulatory approaches reviewed for this report include capacity and non-capacity amendments, adding capacity during relicensing, and adding capacity when converting a license to a 10-MW exemption.« less

Network analysis of surgical innovation: Measuring value and the virality of diffusion in robotic surgery.

PubMed

Garas, George; Cingolani, Isabella; Panzarasa, Pietro; Darzi, Ara; Athanasiou, Thanos

2017-01-01

Existing surgical innovation frameworks suffer from a unifying limitation, their qualitative nature. A rigorous approach to measuring surgical innovation is needed that extends beyond detecting simply publication, citation, and patent counts and instead uncovers an implementation-based value from the structure of the entire adoption cascades produced over time by diffusion processes. Based on the principles of evidence-based medicine and existing surgical regulatory frameworks, the surgical innovation funnel is described. This illustrates the different stages through which innovation in surgery typically progresses. The aim is to propose a novel and quantitative network-based framework that will permit modeling and visualizing innovation diffusion cascades in surgery and measuring virality and value of innovations. Network analysis of constructed citation networks of all articles concerned with robotic surgery (n = 13,240, Scopus®) was performed (1974-2014). The virality of each cascade was measured as was innovation value (measured by the innovation index) derived from the evidence-based stage occupied by the corresponding seed article in the surgical innovation funnel. The network-based surgical innovation metrics were also validated against real world big data (National Inpatient Sample-NIS®). Rankings of surgical innovation across specialties by cascade size and structural virality (structural depth and width) were found to correlate closely with the ranking by innovation value (Spearman's rank correlation coefficient = 0.758 (p = 0.01), 0.782 (p = 0.008), 0.624 (p = 0.05), respectively) which in turn matches the ranking based on real world big data from the NIS® (Spearman's coefficient = 0.673;p = 0.033). Network analysis offers unique new opportunities for understanding, modeling and measuring surgical innovation, and ultimately for assessing and comparing generative value between different specialties. The novel surgical innovation metrics developed may prove valuable especially in guiding policy makers, funding bodies, surgeons, and healthcare providers in the current climate of competing national priorities for investment.

Network analysis of surgical innovation: Measuring value and the virality of diffusion in robotic surgery

PubMed Central

Cingolani, Isabella; Panzarasa, Pietro; Darzi, Ara; Athanasiou, Thanos

2017-01-01

Background Existing surgical innovation frameworks suffer from a unifying limitation, their qualitative nature. A rigorous approach to measuring surgical innovation is needed that extends beyond detecting simply publication, citation, and patent counts and instead uncovers an implementation-based value from the structure of the entire adoption cascades produced over time by diffusion processes. Based on the principles of evidence-based medicine and existing surgical regulatory frameworks, the surgical innovation funnel is described. This illustrates the different stages through which innovation in surgery typically progresses. The aim is to propose a novel and quantitative network-based framework that will permit modeling and visualizing innovation diffusion cascades in surgery and measuring virality and value of innovations. Materials and methods Network analysis of constructed citation networks of all articles concerned with robotic surgery (n = 13,240, Scopus®) was performed (1974–2014). The virality of each cascade was measured as was innovation value (measured by the innovation index) derived from the evidence-based stage occupied by the corresponding seed article in the surgical innovation funnel. The network-based surgical innovation metrics were also validated against real world big data (National Inpatient Sample–NIS®). Results Rankings of surgical innovation across specialties by cascade size and structural virality (structural depth and width) were found to correlate closely with the ranking by innovation value (Spearman’s rank correlation coefficient = 0.758 (p = 0.01), 0.782 (p = 0.008), 0.624 (p = 0.05), respectively) which in turn matches the ranking based on real world big data from the NIS® (Spearman’s coefficient = 0.673;p = 0.033). Conclusion Network analysis offers unique new opportunities for understanding, modeling and measuring surgical innovation, and ultimately for assessing and comparing generative value between different specialties. The novel surgical innovation metrics developed may prove valuable especially in guiding policy makers, funding bodies, surgeons, and healthcare providers in the current climate of competing national priorities for investment. PMID:28841648

76 FR 32331 - Preliminary Plan for Retrospective Review of Existing Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... review. In addition, DHS launched an IdeaScale Web page; this social media tool provided an additional... agency's regulatory program more effective or less burdensome in achieving its regulatory objectives. DHS...

A visualization framework for design and evaluation

NASA Astrophysics Data System (ADS)

Blundell, Benjamin J.; Ng, Gary; Pettifer, Steve

2006-01-01

The creation of compelling visualisation paradigms is a craft often dominated by intuition and issues of aesthetics, with relatively few models to support good design. The majority of problem cases are approached by simply applying a previously evaluated visualisation technique. A large body of work exists covering the individual aspects of visualisation design such as the human cognition aspects visualisation methods for specific problem areas, psychology studies and so forth, yet most frameworks regarding visualisation are applied after-the-fact as an evaluation measure. We present an extensible framework for visualisation aimed at structuring the design process, increasing decision traceability and delineating the notions of function, aesthetics and usability. The framework can be used to derive a set of requirements for good visualisation design and evaluating existing visualisations, presenting possible improvements. Our framework achieves this by being both broad and general, built on top of existing works, with hooks for extensions and customizations. This paper shows how existing theories of information visualisation fit into the scheme, presents our experience in the application of this framework on several designs, and offers our evaluation of the framework and the designs studied.

Using game theory to analyze green stormwater infrastructure implementation policies

NASA Astrophysics Data System (ADS)

William, R. K.; Garg, J.; Stillwell, A. S.

2017-12-01

While green stormwater infrastructure is a useful approach in addressing multiple challenges facing the urban environment, little consensus exists on how to best incentivize its adoption by private landowners. Game theory, a field of study designed to model conflict and cooperation between two or more agents, is well-suited to address this policy question. We used a cooperative game theory framework to analyze the impacts of three different policy approaches frequently used to incentivize the uptake of green infrastructure by private landowners: municipal regulation, direct grants, and stormwater fees. The results indicate that municipal regulation leads to the greatest environmental benefits; however, the choice of "best" regulatory approach is dependent on a variety of different factors including political and financial considerations. Policy impacts are also highly dependent on agents' spatial positions within the stormwater network. This finding leads to important questions of social equity and environmental justice.

Proceedings of the International Summit on Human Gene Editing: a global discussion-Washington, D.C., December 1-3, 2015.

PubMed

LaBarbera, Andrew R

2016-09-01

The US Academies of Sciences and Medicine, the Royal Society, and the Chinese Academy of Sciences convened a summit of experts in biology, medicine, law, ethics, sociology, and journalism, in December 2015 to review the state of the art in gene editing technology and discuss the medical and social ramifications of the technologies. The summit concluded with the following consensus recommendations: (1) intensive basic and preclinical research in animal and human models should proceed with appropriate legal and ethical oversight; (2) clinical applications in somatic cells must be rigorously evaluated within existing and evolving regulatory frameworks for gene therapy; (3) it would be irresponsible to proceed with any clinical use of germline editing until relevant safety and efficacy issues have been resolved and there is broad societal consensus about such a use; and (4) the international community should strive to establish generally acceptable uses of human germline editing.

Flavoured tobacco products and the public's health: lessons from the TPSAC menthol report.

PubMed

Samet, Jonathan M; Pentz, Mary Ann; Unger, Jennifer B

2016-11-01

The menthol report developed by the Tobacco Products Scientific Advisory Committee (TPSAC) of the Center for Tobacco Products elaborated a methodology for considering the public health impact of menthol in cigarettes that has relevance to flavourings generally. The TPSAC report was based on a conceptual framework on how menthol in cigarettes has public health impact results of evidence from related systematic reviews, and an evidence-based statistical model. In extending this approach to flavourings generally, consideration will need to be given to the existence of multiple flavourings, a very dynamic market place and regulatory interventions and industry activities. Now is the time to begin to develop the research strategies and models needed to extend the TPSAC approach to flavoured tobacco products generally. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Integrating patient safety into the clinical microsystem

PubMed Central

Mohr, J; Batalden, P; Barach, P

2004-01-01

Healthcare institutions continue to face challenges in providing safe patient care in increasingly complex organisational and regulatory environments while striving to maintain financial viability. The clinical microsystem provides a conceptual and practical framework for approaching organisational learning and delivery of care. Tensions exist between the conceptual theory and the daily practical applications of providing safe and effective care within healthcare systems. Healthcare organisations are often complex, disorganised, and opaque systems to their users and their patients. This disorganisation may lead to patient discomfort and harm as well as much waste. Healthcare organisations are in some sense conglomerates of smaller systems, not coherent monolithic organisations. The microsystem unit allows organisational leaders to embed quality and safety into a microsystem's developmental journey. Leaders can set the stage for making safety a priority for the organisation while allowing individual microsystems to create innovative strategies for improvement. PMID:15576690

Implications of agricultural and wildlife policy on management and eradication of bovine tuberculosis and brucellosis in free-ranging wood bison of northern Canada.

PubMed

Nishi, J S; Stephen, C; Elkin, B T

2002-10-01

Although disease is often an important factor in the population dynamics of wild ungulates, it is largely the threat-both real and perceived-that sylvatic disease reservoirs pose to the health status of commercial livestock or game farm industry that has led governments to establish policy and legislation for disease management, trade, and movement. With respect to bovine tuberculosis and brucellosis in wildlife, policies are largely borrowed from the existing regulatory framework for domestic livestock. In this paper, we review how general policy goals for managing these reportable diseases in domestic livestock have also affected conservation and management of bison in Canada. We argue that there is a need to better integrate conservation biology with agricultural livestock policy to develop management options and better address the unique conservation challenges that diseased free-ranging bison populations present.

Safety Assessment for a Surface Repository in the Chernobyl Exclusion Zone - Methodology for Assessing Disposal under Intervention Conditions - 13476

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

Haverkamp, B.; Krone, J.; Shybetskyi, I.

The Radioactive Waste Disposal Facility (RWDF) Buryakovka was constructed in 1986 as part of the intervention measures after the accident at Chernobyl NPP (ChNPP). Today, RWDF Buryakovka is still being operated but its maximum capacity is nearly reached. Plans for enlargement of the facility exist since more than 10 years but have not been implemented yet. In the framework of an European Commission Project DBE Technology GmbH prepared a safety analysis report of the facility in its current state (SAR) and a preliminary safety analysis report (PSAR) based on the planned enlargement. Due to its history RWDF Buryakovka does notmore » fully comply with today's best international practices and the latest Ukrainian regulations in this area. The most critical aspects are its inventory of long-lived radionuclides, and the non-existent multi-barrier waste confinement system. A significant part of the project was dedicated, therefore, to the development of a methodology for the safety assessment taking into consideration the facility's special situation and to reach an agreement with all stakeholders involved in the later review and approval procedure of the safety analysis reports. Main aspect of the agreed methodology was to analyze the safety, not strictly based on regulatory requirements but on the assessment of the actual situation of the facility including its location within the Exclusion Zone. For both safety analysis reports, SAR and PSAR, the assessment of the long-term safety led to results that were either within regulatory limits or within the limits allowing for a specific situational evaluation by the regulator. (authors)« less

77 FR 7980 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

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

75 FR 79811 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

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

75 FR 21839 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

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

Project Cerberus: tobacco industry strategy to create an alternative to the Framework Convention on Tobacco Control.

PubMed

Mamudu, Hadii M; Hammond, Ross; Glantz, Stanton A

2008-09-01

Between 1999 and 2001, British American Tobacco, Philip Morris, and Japan Tobacco International executed Project Cerberus to develop a global voluntary regulatory regime as an alternative to the Framework Convention on Tobacco Control (FCTC). They aimed to develop a global voluntary regulatory code to be overseen by an independent audit body and to focus attention on youth smoking prevention. The International Tobacco Products Marketing Standards announced in September 2001, however, did not have the independent audit body. Although the companies did not stop the FCTC, they continue to promote the International Tobacco Products Marketing Standards youth smoking prevention as an alternative to the FCTC. Public health civil society groups should help policymakers and governments understand the importance of not working with the tobacco industry.

Project Cerberus: Tobacco Industry Strategy to Create an Alternative to the Framework Convention on Tobacco Control

PubMed Central

Mamudu, Hadii M.; Hammond, Ross; Glantz, Stanton A.

2008-01-01

Between 1999 and 2001, British American Tobacco, Philip Morris, and Japan Tobacco International executed Project Cerberus to develop a global voluntary regulatory regime as an alternative to the Framework Convention on Tobacco Control (FCTC). They aimed to develop a global voluntary regulatory code to be overseen by an independent audit body and to focus attention on youth smoking prevention. The International Tobacco Products Marketing Standards announced in September 2001, however, did not have the independent audit body. Although the companies did not stop the FCTC, they continue to promote the International Tobacco Products Marketing Standards youth smoking prevention as an alternative to the FCTC. Public health civil society groups should help policymakers and governments understand the importance of not working with the tobacco industry. PMID:18633079

Measuring and Modeling the U.S. Regulatory Ecosystem

NASA Astrophysics Data System (ADS)

Bommarito, Michael J., II; Katz, Daniel Martin

2017-09-01

Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

Let it grow-the open market solution to marijuana control.

PubMed

Gettman, Jon; Kennedy, Michael

2014-11-18

This commentary evaluates regulatory frameworks for the legalized production, sale, and use of marijuana. Specifically, we argue that the primary goal of legalization should be the elimination of the illicit trade in marijuana and that maximizing market participation through open markets and personal cultivation is the best approach to achieving this goal. This argument is based on the assertion that regulatory models based on a tightly controlled government market will fail because they replicate the fatal flaws of the prohibition model. This commentary argues that an examination of the reasons for prohibition's failure-to wit, the inability of government to control the production of marijuana-completely undercuts the basic premise of a tightly controlled market, which depends on the ability of the government to control production. The public interest would be better served by an effective regulatory framework which recognizes and takes advantage of competitive market forces. This analysis argues that reducing teenage access to marijuana requires the elimination of an overcapitalized illicit market. Further, it asserts that this goal and maximization of tax revenue from a legal marijuana market are mutually exclusive objectives.

Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states

PubMed Central

Jang, Sumin; Choubey, Sandeep; Furchtgott, Leon; Zou, Ling-Nan; Doyle, Adele; Menon, Vilas; Loew, Ethan B; Krostag, Anne-Rachel; Martinez, Refugio A; Madisen, Linda; Levi, Boaz P; Ramanathan, Sharad

2017-01-01

The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development. DOI: http://dx.doi.org/10.7554/eLife.20487.001 PMID:28296635

Pan-cancer analysis of somatic copy number alterations implicates IRS4 and IGF2 in enhancer hijacking

PubMed Central

Weischenfeldt, Joachim; Dubash, Taronish; Drainas, Alexandros P.; Mardin, Balca R.; Chen, Yuanyuan; Stütz, Adrian M.; Waszak, Sebastian M.; Bosco, Graziella; Halvorsen, Ann Rita; Raeder, Benjamin; Efthymiopoulos, Theocharis; Erkek, Serap; Siegl, Christine; Brenner, Hermann; Brustugun, Odd Terje; Dieter, Sebastian M.; Northcott, Paul A.; Petersen, Iver; Pfister, Stefan M.; Schneider, Martin; Solberg, Steinar K.; Thunissen, Erik; Weichert, Wilko; Zichner, Thomas; Thomas, Roman; Peifer, Martin; Helland, Aslaug; Ball, Claudia R.; Jechlinger, Martin; Sotillo, Rocio; Glimm, Hanno; Korbel, Jan O.

2018-01-01

Extensive prior research has focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearranging cis-regulatory elements remains unclear. Here, we present a framework for inferring cancer-related gene overexpression resulting from cis-regulatory element reorganization (e.g., enhancer hijacking), by integrating SCNAs, gene expression data, and information on chromatin interaction domains. Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer associates with recurrent deletions in cis, and present evidence supporting a tumor-promoting role. We additionally pursued cancer type-specific analyses, uncovering IGF2 as a target for enhancer hijacking in colorectal cancer. IGF2-containing tandem duplications result in the de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, which mediates high-level gene activation. Our framework enables systematic inference of cis-regulatory element rearrangements mediating dysregulation in cancer. PMID:27869826

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

USGS Publications Warehouse

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

2001-01-01

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

An Integrative Framework for Bayesian Variable Selection with Informative Priors for Identifying Genes and Pathways

PubMed Central

Ander, Bradley P.; Zhang, Xiaoshuai; Xue, Fuzhong; Sharp, Frank R.; Yang, Xiaowei

2013-01-01

The discovery of genetic or genomic markers plays a central role in the development of personalized medicine. A notable challenge exists when dealing with the high dimensionality of the data sets, as thousands of genes or millions of genetic variants are collected on a relatively small number of subjects. Traditional gene-wise selection methods using univariate analyses face difficulty to incorporate correlational, structural, or functional structures amongst the molecular measures. For microarray gene expression data, we first summarize solutions in dealing with ‘large p, small n’ problems, and then propose an integrative Bayesian variable selection (iBVS) framework for simultaneously identifying causal or marker genes and regulatory pathways. A novel partial least squares (PLS) g-prior for iBVS is developed to allow the incorporation of prior knowledge on gene-gene interactions or functional relationships. From the point view of systems biology, iBVS enables user to directly target the joint effects of multiple genes and pathways in a hierarchical modeling diagram to predict disease status or phenotype. The estimated posterior selection probabilities offer probabilitic and biological interpretations. Both simulated data and a set of microarray data in predicting stroke status are used in validating the performance of iBVS in a Probit model with binary outcomes. iBVS offers a general framework for effective discovery of various molecular biomarkers by combining data-based statistics and knowledge-based priors. Guidelines on making posterior inferences, determining Bayesian significance levels, and improving computational efficiencies are also discussed. PMID:23844055

An integrative framework for Bayesian variable selection with informative priors for identifying genes and pathways.

PubMed

Peng, Bin; Zhu, Dianwen; Ander, Bradley P; Zhang, Xiaoshuai; Xue, Fuzhong; Sharp, Frank R; Yang, Xiaowei

2013-01-01

The discovery of genetic or genomic markers plays a central role in the development of personalized medicine. A notable challenge exists when dealing with the high dimensionality of the data sets, as thousands of genes or millions of genetic variants are collected on a relatively small number of subjects. Traditional gene-wise selection methods using univariate analyses face difficulty to incorporate correlational, structural, or functional structures amongst the molecular measures. For microarray gene expression data, we first summarize solutions in dealing with 'large p, small n' problems, and then propose an integrative Bayesian variable selection (iBVS) framework for simultaneously identifying causal or marker genes and regulatory pathways. A novel partial least squares (PLS) g-prior for iBVS is developed to allow the incorporation of prior knowledge on gene-gene interactions or functional relationships. From the point view of systems biology, iBVS enables user to directly target the joint effects of multiple genes and pathways in a hierarchical modeling diagram to predict disease status or phenotype. The estimated posterior selection probabilities offer probabilitic and biological interpretations. Both simulated data and a set of microarray data in predicting stroke status are used in validating the performance of iBVS in a Probit model with binary outcomes. iBVS offers a general framework for effective discovery of various molecular biomarkers by combining data-based statistics and knowledge-based priors. Guidelines on making posterior inferences, determining Bayesian significance levels, and improving computational efficiencies are also discussed.

NPDES Permit Writers' Course

EPA Pesticide Factsheets

The objective of the NPDES permit writers' course is to provide the basic regulatory framework and technical considerations that support the development of wastewater discharge permits as required under the NPDES Permit Program.

Framework for the quantitative weight-of-evidence analysis of 'omics data for regulatory purposes.

PubMed

Bridges, Jim; Sauer, Ursula G; Buesen, Roland; Deferme, Lize; Tollefsen, Knut E; Tralau, Tewes; van Ravenzwaay, Ben; Poole, Alan; Pemberton, Mark

2017-12-01

A framework for the quantitative weight-of-evidence (QWoE) analysis of 'omics data for regulatory purposes is presented. The QWoE framework encompasses seven steps to evaluate 'omics data (also together with non-'omics data): (1) Hypothesis formulation, identification and weighting of lines of evidence (LoEs). LoEs conjoin different (types of) studies that are used to critically test the hypothesis. As an essential component of the QWoE framework, step 1 includes the development of templates for scoring sheets that predefine scoring criteria with scores of 0-4 to enable a quantitative determination of study quality and data relevance; (2) literature searches and categorisation of studies into the pre-defined LoEs; (3) and (4) quantitative assessment of study quality and data relevance using the respective pre-defined scoring sheets for each study; (5) evaluation of LoE-specific strength of evidence based upon the study quality and study relevance scores of the studies conjoined in the respective LoE; (6) integration of the strength of evidence from the individual LoEs to determine the overall strength of evidence; (7) characterisation of uncertainties and conclusion on the QWoE. To put the QWoE framework in practice, case studies are recommended to confirm the relevance of its different steps, or to adapt them as necessary. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

76 FR 69613 - Special Local Regulations and Safety Zones; Recurring Events in Captain of the Port New York Zone

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-09

... regulatory text: Safety zones listed in Table 1 to Sec. 165.160 have been reordered and renumbered to more accurately reflect their geographical locations. In the published NPRM regulatory text, the Rumson, NJ... included in this recurring events regulation. In the regulatory text under Sec. 165.160(a), the existing...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

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

78 FR 40243 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Amendment No. 3 and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... framework. \\17\\ Id. Operational Resources. ICE Clear Europe believes it will have the operational and... governance framework. \\33\\ 15 U.S.C. 78q-1(b)(3)(F). IV. Conclusion On the basis of the foregoing, the... having a U.S. residence, based upon the location of its executive office or principal place of business...

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

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

Grabaskas, David; Bucknor, Matthew; Jerden, James

2016-02-01

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

An approach to predict water quality in data-sparse catchments using hydrological catchment similarity

NASA Astrophysics Data System (ADS)

Pohle, Ina; Glendell, Miriam; Stutter, Marc I.; Helliwell, Rachel C.

2017-04-01

An understanding of catchment response to climate and land use change at a regional scale is necessary for the assessment of mitigation and adaptation options addressing diffuse nutrient pollution. It is well documented that the physicochemical properties of a river ecosystem respond to change in a non-linear fashion. This is particularly important when threshold water concentrations, relevant to national and EU legislation, are exceeded. Large scale (regional) model assessments required for regulatory purposes must represent the key processes and mechanisms that are more readily understood in catchments with water quantity and water quality data monitored at high spatial and temporal resolution. While daily discharge data are available for most catchments in Scotland, nitrate and phosphorus are mostly available on a monthly basis only, as typified by regulatory monitoring. However, high resolution (hourly to daily) water quantity and water quality data exist for a limited number of research catchments. To successfully implement adaptation measures across Scotland, an upscaling from data-rich to data-sparse catchments is required. In addition, the widespread availability of spatial datasets affecting hydrological and biogeochemical responses (e.g. soils, topography/geomorphology, land use, vegetation etc.) provide an opportunity to transfer predictions between data-rich and data-sparse areas by linking processes and responses to catchment attributes. Here, we develop a framework of catchment typologies as a prerequisite for transferring information from data-rich to data-sparse catchments by focusing on how hydrological catchment similarity can be used as an indicator of grouped behaviours in water quality response. As indicators of hydrological catchment similarity we use flow indices derived from observed discharge data across Scotland as well as hydrological model parameters. For the latter, we calibrated the lumped rainfall-runoff model TUWModel using multiple objective functions. The relationships between indicators of hydrological catchment similarity, physical catchment characteristics and nitrate and phosphorus concentrations in rivers are then investigated using multivariate statistics. This understanding of the relationship between catchment characteristics, hydrological processes and water quality will allow us to implement more efficient regulatory water quality monitoring strategies, to improve existing water quality models and to model mitigation and adaptation scenarios to global change in data-sparse catchments.

Drug Development for Pediatric Populations: Regulatory Aspects

PubMed Central

Zisowsky, Jochen; Krause, Andreas; Dingemanse, Jasper

2010-01-01

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

Intrinsic limits to gene regulation by global crosstalk

PubMed Central

Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

2016-01-01

Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

78 FR 77736 - Sunshine Act Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... a.m. Briefing on Spent Fuel Pool Safety and Consideration of Expedited Transfer of Spent Fuel to Dry... Disposition Fukushima Near-Term Task Force (NTTF) Recommendation 1 on Improving NRC's Regulatory Framework...

Making habitat connectivity a reality.

PubMed

Keeley, Annika T H; Basson, Galli; Cameron, D Richard; Heller, Nicole E; Huber, Patrick R; Schloss, Carrie A; Thorne, James H; Merenlender, Adina M

2018-06-19

For over 40 years, habitat corridors have been a solution for sustaining wildlife in fragmented landscapes, and now are often suggested as a climate adaptation strategy. However, while a plethora of connectivity plans exist, protecting and restoring habitat connectivity through on-the-ground action has been slow. We identified implementation challenges and opportunities through a literature review of project implementation, a science-practice workshop, and interviews with conservation professionals. Our research indicates that connectivity challenges and solutions tend to be context-specific, dependent on land ownership patterns, socioeconomic factors, and the policy framework. We found evidence that developing and promoting a common vision shared by a diverse set of stakeholders including nontraditional conservation actors, such as water districts and recreation departments, and through communication among and between partners and the public is key to successful implementation. Other factors that lead to successful implementation include undertaking empirical studies to prioritize and validate corridors and the identification of related co-benefits of corridor projects. Engaging partners involved in land management and planning, such as non-governmental conservation organizations, public agencies, and private landowners is critical to effective strategy implementation. A clear regulatory framework including unambiguous connectivity conservation mandates would increase public resource allocation, and incentive programs are needed to promote private sector engagement. We argue that connectivity conservation must more rapidly move from planning to implementation and provide an evidence-based solution made up of key elements for successful on-the-ground connectivity implementation. The components of this new framework constitute the social processes necessary to advance habitat connectivity for biodiversity conservation and resilient landscapes under climate change. Three case studies serve to illustrate the application of the framework. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality

PubMed Central

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G.; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H.; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

Objective To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. Study design and setting We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Results Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Conclusion Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders’ individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research. PMID:28715491

A framework to find the logic backbone of a biological network.

PubMed

Maheshwari, Parul; Albert, Réka

2017-12-06

Cellular behaviors are governed by interaction networks among biomolecules, for example gene regulatory and signal transduction networks. An often used dynamic modeling framework for these networks, Boolean modeling, can obtain their attractors (which correspond to cell types and behaviors) and their trajectories from an initial state (e.g. a resting state) to the attractors, for example in response to an external signal. The existing methods however do not elucidate the causal relationships between distant nodes in the network. In this work, we propose a simple logic framework, based on categorizing causal relationships as sufficient or necessary, as a complement to Boolean networks. We identify and explore the properties of complex subnetworks that are distillable into a single logic relationship. We also identify cyclic subnetworks that ensure the stabilization of the state of participating nodes regardless of the rest of the network. We identify the logic backbone of biomolecular networks, consisting of external signals, self-sustaining cyclic subnetworks (stable motifs), and output nodes. Furthermore, we use the logic framework to identify crucial nodes whose override can drive the system from one steady state to another. We apply these techniques to two biological networks: the epithelial-to-mesenchymal transition network corresponding to a developmental process exploited in tumor invasion, and the network of abscisic acid induced stomatal closure in plants. We find interesting subnetworks with logical implications in these networks. Using these subgraphs and motifs, we efficiently reduce both networks to succinct backbone structures. The logic representation identifies the causal relationships between distant nodes and subnetworks. This knowledge can form the basis of network control or used in the reverse engineering of networks.

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality.

PubMed

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders' individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research.

Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes

PubMed Central

Sethi, Isha; Gluck, Christian; Zhou, Huiqing

2017-01-01

Abstract Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species could arise in part, by the rewiring of regulatory network due to changes in the global targets of lineage-specific transcriptional master regulators such as p63. Here we have performed a systematic and comparative analysis of the p63 target gene network within the integrated framework of the transcriptomic and epigenomic landscape of mouse and human keratinocytes. We determined that there exists a core set of ∼1600 genomic regions distributed among enhancers and super-enhancers, which are conserved and occupied by p63 in keratinocytes from both species. Notably, these DNA segments are typified by consensus p63 binding motifs under purifying selection and are associated with genes involved in key keratinocyte and skin-centric biological processes. However, the majority of the p63-bound mouse target regions consist of either murine-specific DNA elements that are not alignable to the human genome or exhibit no p63 binding in the orthologous syntenic regions, typifying an occupancy lost subset. Our results suggest that these evolutionarily divergent regions have undergone significant turnover of p63 binding sites and are associated with an underlying inactive and inaccessible chromatin state, indicative of their selective functional activity in the transcriptional regulatory network in mouse but not human. Furthermore, we demonstrate that this selective targeting of genes by p63 correlates with subtle, but measurable transcriptional differences in mouse and human keratinocytes that converges on major metabolic processes, which often exhibit species-specific trends. Collectively our study offers possible molecular explanation for the observable phenotypic differences between the mouse and human skin and broadly informs on the prevailing principles that govern the tug-of-war between evolutionary forces of rigidity and plasticity over transcriptional regulatory programs. PMID:28505376

Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances.

PubMed Central

Cronin, Mark T D; Walker, John D; Jaworska, Joanna S; Comber, Michael H I; Watts, Christopher D; Worth, Andrew P

2003-01-01

This article is a review of the use, by regulatory agencies and authorities, of quantitative structure-activity relationships (QSARs) to predict ecologic effects and environmental fate of chemicals. For many years, the U.S. Environmental Protection Agency has been the most prominent regulatory agency using QSARs to predict the ecologic effects and environmental fate of chemicals. However, as increasing numbers of standard QSAR methods are developed and validated to predict ecologic effects and environmental fate of chemicals, it is anticipated that more regulatory agencies and authorities will find them to be acceptable alternatives to chemical testing. PMID:12896861

Standalone medical device software: The evolving regulatory framework.

PubMed

McCarthy, Avril D; Lawford, Patricia V

2014-01-01

The paper provides an introduction to the regulatory landscape affecting a particular category of medical technology, namely standalone software-sometimes referred to as 'software as a medical device'. To aid the reader's comprehension of an often complex area, six case studies are outlined and discussed before the paper continues to provide detail of how software with a medical purpose in its own right can potentially be classified as a medical device. The reader is provided an appreciation of how to go about classifying such software and references to support the developer new to the field in locating detailed regulatory support documents and contact points for advice.

77 FR 65645 - Retrospective Analysis of Existing Rules: Notice of Staff Memorandum

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

...] Retrospective Analysis of Existing Rules: Notice of Staff Memorandum SUMMARY: Take notice that the Commission... Analysis of Existing Rules prepared in response to Executive Order 13579, which requested independent regulatory agencies issue plans for periodic retrospective analysis of their existing regulations. [[Page...

Principles and perspectives.

PubMed

Steinhäuser, Klaus Günter; Richter, Steffi; Greiner, Petra; Penning, Jutta; Angrick, Michael

2004-01-01

With respect to the enormous increase of chemical production in the last decades and the tens of thousands of individual chemicals on the market, the permanent improvement of chemical management is a permanent target to achieve the goals of sustainable consumption and production set by the WSSD in Johannesburg 2002. Several approaches exist to describe sustainability of chemistry. However, commonly agreed criteria are still missing. There is no doubt that products of modern chemistry help to achieve important goals of sustainability and that significant improvements have occurred regarding direct releases from production sites, but several facts demonstrate that chemistry is far from being sustainable. Still too many chemicals exhibit hazardous characteristics and pose a risk to health and environment. Too many resources are needed to produce chemicals and finished products. Therefore, a strategy for sustainability of chemistry should be developed which comprises the following main elements: 1. Sustainable chemicals: sustainable chemical management includes a regulatory framework which makes no difference between new and existing chemicals, contains efficient information flow through the supply chain which allows users to handle chemicals safely and offers an authorisation procedure and/or an efficient restriction procedure for substances of high concern. This regulatory scheme should promote the development of inherently safe chemicals. 2. Sustainable chemical production: Sustainable chemical production needs the development and implementation of emerging alternative techniques like selective catalysis, biotechnology in order to release less CO2 and less toxic by-products, to save energy and to achieve higher yields. Information exchange on best available techniques (BAT) and best environmental practices (BEP) may help to promote changes towards more sustainability. 3. Sustainable products: An integrated product policy which provides a framework for sustainable products promotes the development of products with a long-term use phase, low resource demand in production and use, low emission of hazardous substances and properties suitable for reuse and recycling. This may be promoted by eco-labelling, chemical leasing concepts and extended information measures to enhance the demand of consumers and various actors in the supply chain for sustainable products. Important tools for the promotion of sustainable chemistry are the abolition of barriers for innovation in legislation and within the chemical industry, more transparency for all users of chemical products, a new focus on sustainability in education and research, and a new way of thinking in terms of sustainability.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

PubMed

Penazzato, Martina; Lewis, Linda; Watkins, Melynda; Prabhu, Vineet; Pascual, Fernando; Auton, Martin; Kreft, Wesley; Morin, Sébastien; Vicari, Marissa; Lee, Janice; Jamieson, David; Siberry, George K

2018-02-01

Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets. © 2018 World Health Organization; licensee IAS.

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

PubMed

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

2014-05-01

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

75 FR 13 - Alternate Fracture Toughness Requirements for Protection Against Pressurized Thermal Shock Events

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-04

...The Nuclear Regulatory Commission (NRC) is amending its regulations to provide alternate fracture toughness requirements for protection against pressurized thermal shock (PTS) events for pressurized water reactor (PWR) pressure vessels. This final rule provides alternate PTS requirements based on updated analysis methods. This action is desirable because the existing requirements are based on unnecessarily conservative probabilistic fracture mechanics analyses. This action reduces regulatory burden for those PWR licensees who expect to exceed the existing requirements before the expiration of their licenses, while maintaining adequate safety, and may choose to comply with the final rule as an alternative to complying with the existing requirements.

The 3’-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells

PubMed Central

Kučerová-Levisohn, Martina; Knirr, Stefan; Mejia, Rosa I.; Ortiz, Benjamin D.

2015-01-01

Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5’ of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCRα transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCRα gene rearrangement, and thus may contribute to endogenous TCRα gene activity, particularly in peripheral T cells, where the Eα element has been found to be inactive. PMID:26177549

Built environment change: a framework to support health-enhancing behaviour through environmental policy and health research.

PubMed

Berke, Ethan M; Vernez-Moudon, Anne

2014-06-01

As research examining the effect of the built environment on health accelerates, it is critical for health and planning researchers to conduct studies and make recommendations in the context of a robust theoretical framework. We propose a framework for built environment change (BEC) related to improving health. BEC consists of elements of the built environment, how people are exposed to and interact with them perceptually and functionally, and how this exposure may affect health-related behaviours. Integrated into this framework are the legal and regulatory mechanisms and instruments that are commonly used to effect change in the built environment. This framework would be applicable to medical research as well as to issues of policy and community planning.

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

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

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

2008-05-12

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

A good chew or good riddance--how to move forward in the regulation of khat consumption.

PubMed

Klein, Axel; Metaal, Pien

2010-12-01

To review the status of khat, the most recent plant based psychoactive substance to reach a global market, and consider policy making processes in general and the framework of drug control in particular. Desk review of literature on khat and wider drug policy processes. The risk assessment and classification of psychoactive drugs is a contested arena where political, economic and moral agendas collide, leaving countries that have banned khat, with significant social costs. To best manage the risks arising from the increasing availability of khat it is therefore suggested to draft a regulatory framework with clear objectives and guiding principles. Given that medical risks of khat use are modest, the objective of the regulatory framework should be the protection of consumers and community. This is best achieved by establishing processes for the quality control of khat imports, and by regulating access and availability. It should therefore not be considered as a drug to be controlled but as a licit substance that needs to be regulated. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The emerging international regulatory framework for biotechnology.

PubMed

Komen, John

2012-01-01

Debate about the potential risks of genetically modified organisms (GMOs) to the environment or human health spurred attention to biosafety. Biosafety is associated with the safe use of GMOs and, more generally, with the introduction of non-indigenous species into natural or managed ecosystems. Biosafety regulation--the policies and procedures adopted to ensure the environmentally safe application of modern biotechnology--has been extensively discussed at various national and international forums. Much of the discussion has focused on developing guidelines, appropriate legal frameworks and, at the international level, a legally binding international biosafety protocol--the Cartagena Protocol on Biosafety. The Protocol is one among various international instruments and treaties that regulate specific aspects relevant to agricultural biotechnology. The present article presents the main international instruments relevant to biosafety regulation, and their key provisions. While international agreements and standards provide important guidance, they leave significant room for interpretation, and flexibility for countries implementing them. Implementation of biosafety at the national level has proven to be a major challenge, particularly in developing countries, and consequently the actual functioning of the international regulatory framework for biotechnology is still in a state of flux.

Biodiversity Conservation in the REDD

PubMed Central

2010-01-01

Deforestation and forest degradation in the tropics is a major source of global greenhouse gas (GHG) emissions. The tropics also harbour more than half the world's threatened species, raising the possibility that reducing GHG emissions by curtailing tropical deforestation could provide substantial co-benefits for biodiversity conservation. Here we explore the potential for such co-benefits in Indonesia, a leading source of GHG emissions from land cover and land use change, and among the most species-rich countries in the world. We show that focal ecosystems for interventions to reduce emissions from deforestation and forest degradation in Indonesia do not coincide with areas supporting the most species-rich communities or highest concentration of threatened species. We argue that inherent trade-offs among ecosystems in emission reduction potential, opportunity cost of foregone development and biodiversity values will require a regulatory framework to balance emission reduction interventions with biodiversity co-benefit targets. We discuss how such a regulatory framework might function, and caution that pursuing emission reduction strategies without such a framework may undermine, not enhance, long-term prospects for biodiversity conservation in the tropics. PMID:21092321

78 FR 37246 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... POSTAL REGULATORY COMMISSION [Docket No. CP2013-67; Order No. 1749] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice SUMMARY: The Commission is noticing a recently filed Postal... the introductory (``Whereas'') paragraphs of the Agreement; revisions to existing articles; and new...

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

NASA Astrophysics Data System (ADS)

Makarovič, Boštjan

2013-07-01

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

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

DTIC Science & Technology

1981-09-24

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

Physico-chemical properties of manufactured nanomaterials - Characterisation and relevant methods. An outlook based on the OECD Testing Programme.

PubMed

Rasmussen, Kirsten; Rauscher, Hubert; Mech, Agnieszka; Riego Sintes, Juan; Gilliland, Douglas; González, Mar; Kearns, Peter; Moss, Kenneth; Visser, Maaike; Groenewold, Monique; Bleeker, Eric A J

2018-02-01

Identifying and characterising nanomaterials require additional information on physico-chemical properties and test methods, compared to chemicals in general. Furthermore, regulatory decisions for chemicals are usually based upon certain toxicological properties, and these effects may not be equivalent to those for nanomaterials. However, regulatory agencies lack an authoritative decision framework for nanomaterials that links the relevance of certain physico-chemical endpoints to toxicological effects. This paper investigates various physico-chemical endpoints and available test methods that could be used to produce such a decision framework for nanomaterials. It presents an overview of regulatory relevance and methods used for testing fifteen proposed physico-chemical properties of eleven nanomaterials in the OECD Working Party on Manufactured Nanomaterials' Testing Programme, complemented with methods from literature, and assesses the methods' adequacy and applications limits. Most endpoints are of regulatory relevance, though the specific parameters depend on the nanomaterial and type of assessment. Size (distribution) is the common characteristic of all nanomaterials and is decisive information for classifying a material as a nanomaterial. Shape is an important particle descriptor. The octanol-water partitioning coefficient is undefined for particulate nanomaterials. Methods, including sample preparation, need to be further standardised, and some new methods are needed. The current work of OECD's Test Guidelines Programme regarding physico-chemical properties is highlighted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

How We Assess Risks to Pollinators

EPA Pesticide Factsheets

EPA's pollinator risk assessment framework is part of its regulatory decision-making process for all pesticides, relying on a tiered process and focusing on major routes of exposure while distinguishing different types of pesticide treatment.

Premise to Implement a Grading System to Evaluate the Sanitary Level in Food Service Establishments in Milan, Italy

PubMed Central

Razzini, Katia

2015-01-01

The regulatory framework of the official controls on food safety, the criteria and methods from the planning of interventions in the field of official control to the management of information flows, and the standards described in the operation manual of the local competent authorities drafted by the Lombardy Region (2011) were evaluated. A questionnaire consisting of n. 10 questions with multiple answers draft in partnership with EPAM (the Association of Provincial Public Retail and catering businesses in Milan) to n. 107 Food service establishments of Milan shows that 92% of managers approve the introduction of a grading system. The regulatory framework is planned to support the implementation of risk assignment, unfortunately the attribution of risk category of retail and catering businesses is still different among regions. PMID:27800403

From Banking to International Governance: Fostering Innovation in Stem Cell Research

PubMed Central

Isasi, Rosario; Knoppers, Bartha M.

2011-01-01

Stem cell banks are increasingly recognized as an essential resource of biological materials for both basic and translational stem cell research. By providing transnational access to quality controlled and ethically sourced stem cell lines, stem cell banks seek to foster international collaboration and innovation. However, given that national stem cell banks operate under different policy, regulatory and commercial frameworks, the transnational sharing of stem cell materials and data can be complicating. This paper will provide an overview of the most pressing challenges regarding the governance of stem cell banks, and the difficulties in designing regulatory and commercial frameworks that foster stem cell research. Moreover, the paper will shed light on the numerous international initiatives that have arisen to help harmonize and standardize stem cell banking and research processes to overcome such challenges. PMID:21904557

Qa-1/HLA-E-restricted regulatory CD8+ T cells and self-nonself discrimination: an essay on peripheral T-cell regulation.

PubMed

Jiang, Hong; Chess, Leonard

2008-11-01

By discriminating self from nonself and controlling the magnitude and class of immune responses, the immune system mounts effective immunity against virtually any foreign antigens but avoids harmful immune responses to self. These are two equally important and related but distinct processes, which function in concert to ensure an optimal function of the immune system. Immunologically relevant clinical problems often occur because of failure of either process, especially the former. Currently, there is no unified conceptual framework to characterize the precise relationship between thymic negative selection and peripheral immune regulation, which is the basis for understanding self-non-self discrimination versus control of magnitude and class of immune responses. In this article, we explore a novel hypothesis of how the immune system discriminates self from nonself in the periphery during adaptive immunity. This hypothesis permits rational analysis of various seemingly unrelated biomedical problems inherent in immunologic disorders that cannot be uniformly interpreted by any currently existing paradigms. The proposed hypothesis is based on a unified conceptual framework of the "avidity model of peripheral T-cell regulation" that we originally proposed and tested, in both basic and clinical immunology, to understand how the immune system achieves self-nonself discrimination in the periphery.

A Framework for Evaluating Economic Impacts of Rooftop PV Systems with or without Energy Storage on Thai Distribution Utilities and Ratepayers

NASA Astrophysics Data System (ADS)

Chaianong, A.; Bangviwat, A.; Menke, C.

2017-07-01

Driven by decreasing PV and energy storage prices, increasing electricity costs and policy supports from Thai government (self-consumption era), rooftop PV and energy storage systems are going to be deployed in the country rapidly that may disrupt existing business models structure of Thai distribution utilities due to revenue erosion and lost earnings opportunities. The retail rates that directly affect ratepayers (non-solar customers) are expected to increase. This paper focuses on a framework for evaluating impacts of PV with and without energy storage systems on Thai distribution utilities and ratepayers by using cost-benefit analysis (CBA). Prior to calculation of cost/benefit components, changes in energy sales need to be addressed. Government policies for the support of PV generation will also help in accelerating the rooftop PV installation. Benefit components include avoided costs due to transmission losses and deferring distribution capacity with appropriate PV penetration level, while cost components consist of losses in revenue, program costs, integration costs and unrecovered fixed costs. It is necessary for Thailand to compare total costs and total benefits of rooftop PV and energy storage systems in order to adopt policy supports and mitigation approaches, such as business model innovation and regulatory reform, effectively.

[The development of the system of medical rehabilitation based at the Russian health resort facilities: investment prospects].

PubMed

Povazhnaya, E L; Gusakova, E V; Moiseenko, S V

2018-05-21

The present work is devoted to the prospects for attracting investments for the maintenance and development of the medical rehabilitation practices based at the Russian health resort facilities. The article describes the prerequisites for the enhancement of the investment attractiveness of the development of the system of medical rehabilitation in the said institutions including the formulation and strengthening of the legal and regulatory framework, the capacity for the organization of the second and third stages of medical rehabilitation in the existing spa and health resort facilities, the attraction of the funds of compulsory medical insurance as an additional source of the financial support. The main legal documents regulating the organization and provision of medical rehabilitation based at the spa and health resort facilities are presented. The results of the implementation of the investment concept of the development of medical rehabilitation in the framework of the system of health resort treatment as exemplified by the experience of JSC «The group of companies «Medsi» are discussed. It is shown that the development of medical rehabilitation based at the spa and health resort facilities greatly contributes to the significant expansion of the potential customer base and promotes the further growth of business scale.

Country Review of Energy-Efficiency Financial Incentives in the Residential Sector

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

Can, Stephane de la Rue du; Shah, Nihar; Phadke, Amol

A large variety of energy-efficiency policy measures exist. Some are mandatory, some are informative, and some use financial incentives to promote diffusion of efficient equipment. From country to country, financial incentives vary considerably in scope and form, the type of framework used to implement them, and the actors that administer them. They range from rebate programs administered by utilities under an Energy-Efficiency Resource Standards (EERS) regulatory framework (California, USA) to the distribution of Eco-points rewarding customers for buying highly efficient appliances (Japan). All have the primary objective of transforming the current market to accelerate the diffusion of efficient technologies bymore » addressing up-front cost barriers faced by consumers; in most instances, efficient technologies require a greater initial investment than conventional technologies. In this paper, we review the different market transformation measures involving the use of financial incentives in the countries belonging to the Major Economies Forum. We characterize the main types of measures, discuss their mechanisms, and provide information on program impacts to the extent that ex-ante or ex-post evaluations have been conducted. Finally, we identify best practices in financial incentive programs and opportunities for coordination between Major Economies Forum countries as envisioned under the Super Efficient Appliance Deployment (SEAD) initiative.« less

Child and adolescent mental health nursing seen through a social constructionist lens.

PubMed

Rasmussen, Philippa; Muir-Cochrane, Eimear; Henderson, Ann

2015-11-01

To discuss the theoretical framework of social constructivism and justify it s appropriateness for and compatibility with an interpretive approach to child adolescent mental health (CAMH) nursing research. Recent changes to national nursing legislation in Australia have resulted in the removal of the separate register with regulatory authorities that existed for the specialty of mental health nursing. Aspects of mental health nursing age are not easily defined, with some being tacit. CAMH nursing is a sub-specialty area of mental health in which the role and function of these nurses is also not overtly understood. An interpretive research study was designed to develop a deeper understanding of the role and work of CAMH nurses when working in an inpatient setting. REVEW METHODS: An interpretive enquiry methodology was used fro the study, with three sequential stages of data collection: document analysis, focus group interviews and semi-structured individual interviews. Social constructionism was the chosen theoretical framework for this study as it provided a useful lens for interpreting and understanding the work of the CAMH nurse. The social constructionist lens was simpatico with mental health nursing, as they both involved making meaning of or assessing information and understanding of social processes and interactions. IMPLICATIONS FOR REEARCH/PRACTICE: A useful lens for further research into mental health nursing practice.

Insights from agriculture for the management of insecticide resistance in disease vectors.

PubMed

Sternberg, Eleanore D; Thomas, Matthew B

2018-04-01

Key to contemporary management of diseases such as malaria, dengue, and filariasis is control of the insect vectors responsible for transmission. Insecticide-based interventions have contributed to declines in disease burdens in many areas, but this progress could be threatened by the emergence of insecticide resistance in vector populations. Insecticide resistance is likewise a major concern in agriculture, where insect pests can cause substantial yield losses. Here, we explore overlaps between understanding and managing insecticide resistance in agriculture and in public health. We have used the Global Plan for Insecticide Resistance Management in malaria vectors, developed under the auspices of the World Health Organization Global Malaria Program, as a framework for this exploration because it serves as one of the few cohesive documents for managing a global insecticide resistance crisis. Generally, this comparison highlights some fundamental differences between insect control in agriculture and in public health. Moreover, we emphasize that the success of insecticide resistance management strategies is strongly dependent on the biological specifics of each system. We suggest that the biological, operational, and regulatory differences between agriculture and public health limit the wholesale transfer of knowledge and practices from one system to the other. Nonetheless, there are some valuable insights from agriculture that could assist in advancing the existing Global Plan for Insecticide Resistance Management framework.

A framework for assessing Health Economic Evaluation (HEE) quality appraisal instruments.

PubMed

Langer, Astrid

2012-08-16

Health economic evaluations support the health care decision-making process by providing information on costs and consequences of health interventions. The quality of such studies is assessed by health economic evaluation (HEE) quality appraisal instruments. At present, there is no instrument for measuring and improving the quality of such HEE quality appraisal instruments. Therefore, the objectives of this study are to establish a framework for assessing the quality of HEE quality appraisal instruments to support and improve their quality, and to apply this framework to those HEE quality appraisal instruments which have been subject to more scrutiny than others, in order to test the framework and to demonstrate the shortcomings of existing HEE quality appraisal instruments. To develop the quality assessment framework for HEE quality appraisal instruments, the experiences of using appraisal tools for clinical guidelines are used. Based on a deductive iterative process, clinical guideline appraisal instruments identified through literature search are reviewed, consolidated, and adapted to produce the final quality assessment framework for HEE quality appraisal instruments. The final quality assessment framework for HEE quality appraisal instruments consists of 36 items organized within 7 dimensions, each of which captures a specific domain of quality. Applying the quality assessment framework to four existing HEE quality appraisal instruments, it is found that these four quality appraisal instruments are of variable quality. The framework described in this study should be regarded as a starting point for appraising the quality of HEE quality appraisal instruments. This framework can be used by HEE quality appraisal instrument producers to support and improve the quality and acceptance of existing and future HEE quality appraisal instruments. By applying this framework, users of HEE quality appraisal instruments can become aware of methodological deficiencies inherent in existing HEE quality appraisal instruments. These shortcomings of existing HEE quality appraisal instruments are illustrated by the pilot test.

A framework for assessing Health Economic Evaluation (HEE) quality appraisal instruments

PubMed Central

2012-01-01

Background Health economic evaluations support the health care decision-making process by providing information on costs and consequences of health interventions. The quality of such studies is assessed by health economic evaluation (HEE) quality appraisal instruments. At present, there is no instrument for measuring and improving the quality of such HEE quality appraisal instruments. Therefore, the objectives of this study are to establish a framework for assessing the quality of HEE quality appraisal instruments to support and improve their quality, and to apply this framework to those HEE quality appraisal instruments which have been subject to more scrutiny than others, in order to test the framework and to demonstrate the shortcomings of existing HEE quality appraisal instruments. Methods To develop the quality assessment framework for HEE quality appraisal instruments, the experiences of using appraisal tools for clinical guidelines are used. Based on a deductive iterative process, clinical guideline appraisal instruments identified through literature search are reviewed, consolidated, and adapted to produce the final quality assessment framework for HEE quality appraisal instruments. Results The final quality assessment framework for HEE quality appraisal instruments consists of 36 items organized within 7 dimensions, each of which captures a specific domain of quality. Applying the quality assessment framework to four existing HEE quality appraisal instruments, it is found that these four quality appraisal instruments are of variable quality. Conclusions The framework described in this study should be regarded as a starting point for appraising the quality of HEE quality appraisal instruments. This framework can be used by HEE quality appraisal instrument producers to support and improve the quality and acceptance of existing and future HEE quality appraisal instruments. By applying this framework, users of HEE quality appraisal instruments can become aware of methodological deficiencies inherent in existing HEE quality appraisal instruments. These shortcomings of existing HEE quality appraisal instruments are illustrated by the pilot test. PMID:22894708

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products: overall perspective and role of the pharmacoepidemiologist.

PubMed

Radawski, Christine; Morrato, Elaine; Hornbuckle, Kenneth; Bahri, Priya; Smith, Meredith; Juhaeri, Juhaeri; Mol, Peter; Levitan, Bennett; Huang, Han-Yao; Coplan, Paul; Li, Hu

2015-12-01

Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE). A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process. No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile. The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process. Copyright © 2015 John Wiley & Sons, Ltd.

A Multi-Agent Framework for Packet Routing in Wireless Sensor Networks

PubMed Central

Ye, Dayon; Zhang, Minji; Yang, Yu

2015-01-01

Wireless sensor networks (WSNs) have been widely investigated in recent years. One of the fundamental issues in WSNs is packet routing, because in many application domains, packets have to be routed from source nodes to destination nodes as soon and as energy efficiently as possible. To address this issue, a large number of routing approaches have been proposed. Although every existing routing approach has advantages, they also have some disadvantages. In this paper, a multi-agent framework is proposed that can assist existing routing approaches to improve their routing performance. This framework enables each sensor node to build a cooperative neighbour set based on past routing experience. Such cooperative neighbours, in turn, can help the sensor to effectively relay packets in the future. This framework is independent of existing routing approaches and can be used to assist many existing routing approaches. Simulation results demonstrate the good performance of this framework in terms of four metrics: average delivery latency, successful delivery ratio, number of live nodes and total sensing coverage. PMID:25928063

Idaho National Laboratory Test Area North: Application of Endpoints to Guide Adaptive Remediation at a Complex Site: INL Test Area North: Application of Endpoints

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

Lee, M. Hope; Truex, Mike; Freshley, Mark

Complex sites are defined as those with difficult subsurface access, deep and/or thick zones of contamination, large areal extent, subsurface heterogeneities that limit the effectiveness of remediation, or where long-term remedies are needed to address contamination (e.g., because of long-term sources or large extent). The Test Area North at the Idaho National Laboratory, developed for nuclear fuel operations and heavy metal manufacturing, is used as a case study. Liquid wastes and sludge from experimental facilities were disposed in an injection well, which contaminated the subsurface aquifer located deep within fractured basalt. The wastes included organic, inorganic, and low-level radioactive constituents,more » with the focus of this case study on trichloroethylene. The site is used as an example of a systems-based framework that provides a structured approach to regulatory processes established for remediation under existing regulations. The framework is intended to facilitate remedy decisions and implementation at complex sites where restoration may be uncertain, require long timeframes, or involve use of adaptive management approaches. The framework facilitates site, regulator, and stakeholder interactions during the remedial planning and implementation process by using a conceptual model description as a technical foundation for decisions, identifying endpoints, which are interim remediation targets or intermediate decision points on the path to an ultimate end, and maintaining protectiveness during the remediation process. At the Test Area North, using a structured approach to implementing concepts in the endpoint framework, a three-component remedy is largely functioning as intended and is projected to meet remedial action objectives by 2095 as required. The remedy approach is being adjusted as new data become available. The framework provides a structured process for evaluating and adjusting the remediation approach, allowing site owners, regulators, and stakeholders to manage contamination at complex sites where adaptive remedies are needed.« less

77 FR 71458 - New International Mail Contract

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... POSTAL REGULATORY COMMISSION [Docket No. CP2013-20; Order No. 1553] New International Mail Contract AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a...\\ Id. at 5-7. \\3\\ Differences include numerous revisions to existing Articles and five new Articles. Id...

78 FR 42566 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... POSTAL REGULATORY COMMISSION [Docket No. CP2013-72; Order No. 1775] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service... Agreement; revisions to several existing articles; and new, deleted, and renumbered articles. Id. at 3-7...

33 CFR 1.05-10 - Regulatory process overview.

Code of Federal Regulations, 2011 CFR

2011-07-01

... regulation, alternatives considered, and potential cost and benefits, including possible environmental... or for changes to an existing regulation. The need may arise due to statutory changes, or be based on... Federal Register. These may include regulatory evaluations, environmental analyses, requests for comments...

33 CFR 1.05-10 - Regulatory process overview.

Code of Federal Regulations, 2010 CFR

2010-07-01

... regulation, alternatives considered, and potential cost and benefits, including possible environmental... or for changes to an existing regulation. The need may arise due to statutory changes, or be based on... Federal Register. These may include regulatory evaluations, environmental analyses, requests for comments...

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

PubMed

Villalbí, Joan R; Pérez, Catherine

2006-03-01

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

MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach.

PubMed

Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L

2017-01-01

Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

Total Water Management: A Watershed Based Approach

EPA Science Inventory

In this urbanizing world, municipal water managers need to develop planning and management frameworks to meet challenges such as limiting fresh water supplies, degrading receiving waters, increasing regulatory requirements, flooding, aging infrastructure, rising utility (energy) ...

Bringing electricity reform to the Philippines

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

Fe Villamejor-Mendoza, Maria

2008-12-15

Electricity reforms will not translate to competition overnight. But reforms are inching their way forward in institutions and stakeholders of the Philippine electricity industry, through regulatory and competition frameworks, processes, and systems promulgated and implemented. (author)

Framework for developing a regional system architecture for intelligent transportation systems

DOT National Transportation Integrated Search

1997-01-01

Defining an architecture for intelligent transportation systems (ITS) at the regional level, where most ITS deployment occurs, is constrained by jurisdictional, institutional, financial, political, and regulatory factors. These constraints provide op...

Total Water Management: A Watershed Based Approach - slides

EPA Science Inventory

ABSTRACT In this urbanizing world, municipal water managers need to develop planning and management frameworks to meet challenges such as limiting fresh water supplies, degrading receiving waters, increasing regulatory requirements, flooding, aging infrastructure, rising utility...

Financial Responsibility for Reentry Vehicle Operations

DOT National Transportation Integrated Search

1995-05-01

The Department of Transportation's Office of Commercial Space Transportation is : in the process of assessing the safety of a reentry vehicle and its operation : and is developing an associated regulatory framework for ensuring public safety : while ...

Sediment Toxicity Testing

EPA Science Inventory

Sediment toxicity testing has become a fundamental component of regulatory frameworks for assessing the risks posed by contaminated sediments and for development of chemical sediment quality guidelines. Over the past two decades, sediment toxicity testing methods have advanced co...

Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.

PubMed

Verbeken, G; Huys, I; De Vos, D; De Coninck, A; Roseeuw, D; Kets, E; Vanderkelen, A; Draye, J P; Rose, T; Jennes, S; Ceulemans, C; Pirnay, J P

2016-02-01

Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pain and Policy Studies Group: Two Decades of Working to Address Regulatory Barriers to Improve Opioid Availability and Accessibility Around the World.

PubMed

Cleary, James F; Maurer, Martha A

2018-02-01

For two decades, the Pain & Policy Studies Group (PPSG), a global research program at the University of Wisconsin Carbone Cancer Center, has worked passionately to fulfill its mission of improving pain relief by achieving balanced access to opioids worldwide. PPSG's early work highlighted the conceptual framework of balance leading to the development of the seminal guidelines and criteria for evaluating opioid policy. It has collaborated at the global level with United Nations agencies to promote access to opioids and has developed a unique model of technical assistance to help national governments assess regulatory barriers to essential medicines for pain relief and amend existing or develop new legislation that facilitates appropriate and adequate opioid prescribing according to international standards. This model was initially applied in regional workshops and individual country projects and then adapted for PPSG's International Pain Policy Fellowship, which provides long-term mentoring and support for several countries simultaneously. The PPSG disseminates its work online in several ways, including an extensive Web site, news alerts, and through several social media outlets. PPSG has become the focal point for expertise on policy governing drug control and medicine and pharmacy practice related to opioid availability and pain relief. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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

Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment thatmore » integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches.« less

Optimizing Ocean Space: Co-siting Open Ocean Aquaculture

NASA Astrophysics Data System (ADS)

Cobb, B. L.; Wickliffe, L. C.; Morris, J. A., Jr.

2016-12-01

In January of 2016, NOAA's National Marine Fisheries Service released the Gulf Aquaculture Plan (GAP) to manage the development of environmentally sound and economically sustainable open ocean finfish aquaculture in the Gulf of Mexico (inside the U.S. Exclusive Economic Zone [EEZ]). The GAP provides the first regulatory framework for aquaculture in federal waters with estimated production of 64 million pounds of finfish, and an estimated economic impact of $264 million annually. The Gulf of Mexico is one of the most industrialized ocean basins in the world, with many existing ocean uses including oil and natural gas production, shipping and commerce, commercial fishing operations, and many protected areas to ensure conservation of valuable ecosystem resources and services. NOAA utilized spatial planning procedures and tools identifying suitable sites for establishing aquaculture through exclusion analyses using authoritative federal and state data housed in a centralized geodatabase. Through a highly collaborative, multi-agency effort a mock permitting exercise was conducted to illustrate the regulatory decision-making process for the Gulf. Further decision-making occurred through exploring co-siting opportunities with oil and natural gas platforms. Logistical co-siting was conducted to reduce overall operational costs by looking at distance to major port and commodity tonnage at each port. Importantly, the process of co-siting allows aquaculture to be coupled with other benefits, including the availability of previously established infrastructure and the reduction of environmental impacts.

Is the risk from nanomaterials perceived as different from the risk of 'chemicals' by the Australian public?

PubMed

Capon, Adam; Rolfe, Margaret; Gillespie, James; Smith, Wayne

2016-04-15

Manufactured nanomaterials in Australia are managed predominantly through existing chemical regulatory frameworks. Many Australian government regulators have suggested the framing of manufactured nanomaterials as 'chemicals' when communicating about manufactured nanomaterials to the general public. This paper aims to determine whether the Australian public perception of manufactured nanomaterials differs to that of 'chemicals', and to examine the relationship between attitudes towards chemicals and perceptions of nanomaterial risk. We undertook a computerised assisted telephone survey of the Australian public. Analysis was undertaken using descriptive, paired tests of proportion, paired t-test and logistic regression techniques. We explored perceptions of nanomaterial risk and their relationship to perceptions of chemical risk and 'chemical attitudes'. We found that the public perceives nanomaterials in a more favourable light than it does chemicals. Perception of risk from chemicals had the greatest association with perceived nanomaterial risk (adjusted odds ratios between 0.1 and 0.2) and that attitudes to chemicals were associated with perception of nanomaterial risk in some cases. Risk communicators and policy makers need to consider the differences and associations between nanomaterials and chemicals when addressing the regulatory aspects of nanomaterials with the public. This is relevant for communication strategies that attempt to normalise the risks from nanomaterials compared with those of chemicals, especially as nanomaterials are perceived to be less risky than chemicals.

Advancing the practice of health impact assessment in Canada: Obstacles and opportunities

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

McCallum, Lindsay C., E-mail: lindsay.mccallum@mail.utoronto.ca; Intrinsik Environmental Sciences Inc., 6605 Hurontario Street, Mississauga, Ontario L5T0A3; Ollson, Christopher A., E-mail: collson@intrinsik.com

Health Impact Assessment (HIA) is recognized as a useful tool that can identify potential health impacts resulting from projects or policy initiatives. Although HIA has become an established practice in some countries, it is not yet an established practice in Canada. In order to enable broader support for HIA, this study provides a comprehensive review and analysis of the peer-reviewed and gray literature on the state of HIA practice. The results of this review revealed that, although there is an abundance of publications relating to HIA, there remains a lack of transparent, consistent and reproducible approaches and methods throughout themore » process. Findings indicate a need for further research and development on a number of fronts, including: 1) the nature of HIA triggers; 2) consistent scoping and stakeholder engagement approaches; 3) use of evidence and transparency of decision-making; 4) reproducibility of assessment methods; 5) monitoring and evaluation protocols; and, 6) integration within existing regulatory frameworks. Addressing these issues will aid in advancing the more widespread use of HIA in Canada. - Highlights: • Reviewed current state of practice in the field of HIA • Identified key obstacles and opportunities for HIA advancement • Major issues include lack of consistent approach and methodology. • No national regulatory driver hinders opportunity for widespread use of HIA. • Identified research opportunities vital to developing HIA practice in Canada.« less

High throughput and miniaturised systems for biodegradability assessments.

PubMed

Cregut, Mickael; Jouanneau, Sulivan; Brillet, François; Durand, Marie-José; Sweetlove, Cyril; Chenèble, Jean-Charles; L'Haridon, Jacques; Thouand, Gérald

2014-01-01

The society demands safer products with a better ecological profile. Regulatory criteria have been developed to prevent risks for human health and the environment, for example, within the framework of the European regulation REACH (Regulation (EC) No 1907, 2006). This has driven industry to consider the development of high throughput screening methodologies for assessing chemical biodegradability. These new screening methodologies must be scalable for miniaturisation, reproducible and as reliable as existing procedures for enhanced biodegradability assessment. Here, we evaluate two alternative systems that can be scaled for high throughput screening and conveniently miniaturised to limit costs in comparison with traditional testing. These systems are based on two dyes as follows: an invasive fluorescent dyes that serves as a cellular activity marker (a resazurin-like dye reagent) and a noninvasive fluorescent oxygen optosensor dye (an optical sensor). The advantages and limitations of these platforms for biodegradability assessment are presented. Our results confirm the feasibility of these systems for evaluating and screening chemicals for ready biodegradability. The optosensor is a miniaturised version of a component already used in traditional ready biodegradability testing, whereas the resazurin dye offers an interesting new screening mechanism for chemical concentrations greater than 10 mg/l that are not amenable to traditional closed bottle tests. The use of these approaches allows generalisation of high throughput screening methodologies to meet the need of developing new compounds with a favourable ecological profile and also assessment for regulatory purpose.

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

PubMed Central

Cronin, Mark T D; Jaworska, Joanna S; Walker, John D; Comber, Michael H I; Watts, Christopher D; Worth, Andrew P

2003-01-01

This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches. PMID:12896862

Features of Pharmaceutical Compounding in the Republic of Tajikistan.

PubMed

Alfred-Ugbenbo, D S; Valiev, A H; Zdoryk, O A; Georgiyants, V A

2017-01-01

Despite the deep assortment of finished pharmaceutical products and the reduction in the number of compounding and hospital pharmacies in the Republic of Tajikistan, the need for extemporal medicinal products is still preserved and remains relevant. This article discusses the practice of compounding in the Republic of Tajikistan. History, laws, limits, regulatory institutions, protocols for compounding pharmacy set up, challenges, equipment, extemporaneous formulations, quality control, and storage within regulatory framework are discussed. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

A resource-dependence model of hospital contract management.

PubMed Central

Alexander, J A; Morrisey, M A

1989-01-01

This study empirically examines the determinants of hospital entry into management contracts with multihospital systems. Using a resource-dependence framework, the study tests whether market conditions, regulatory climate, management effectiveness, and certain enabling factors affect the probability of hospital entry into a contract management arrangement. The study used a pooled sample of 312 contract-managed and 936 traditionally managed hospitals. Results suggest the importance of management effectiveness, regulatory climate, and hospital ownership (investor owned or nonprofit) as predisposing conditions of contract management. PMID:2732059

Regulatory aspects of total product life cycle.

PubMed

Hausman, Ethan D; Altaie, Sousan S

2004-12-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

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

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

NASA Astrophysics Data System (ADS)

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

2004-09-01

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

Integrating legal liabilities in nanomanufacturing risk management.

PubMed

Mohan, Mayank; Trump, Benjamin D; Bates, Matthew E; Monica, John C; Linkov, Igor

2012-08-07

Among other things, the wide-scale development and use of nanomaterials is expected to produce costly regulatory and civil liabilities for nanomanufacturers due to lingering uncertainties, unanticipated effects, and potential toxicity. The life-cycle environmental, health, and safety (EHS) risks of nanomaterials are currently being studied, but the corresponding legal risks have not been systematically addressed. With the aid of a systematic approach that holistically evaluates and accounts for uncertainties about the inherent properties of nanomaterials, it is possible to provide an order of magnitude estimate of liability risks from regulatory and litigious sources based on current knowledge. In this work, we present a conceptual framework for integrating estimated legal liabilities with EHS risks across nanomaterial life-cycle stages using empirical knowledge in the field, scientific and legal judgment, probabilistic risk assessment, and multicriteria decision analysis. Such estimates will provide investors and operators with a basis to compare different technologies and practices and will also inform regulatory and legislative bodies in determining standards that balance risks with technical advancement. We illustrate the framework through the hypothetical case of a manufacturer of nanoscale titanium dioxide and use the resulting expected legal costs to evaluate alternative risk-management actions.

BREAD: a European coordination action for broadband for all

NASA Astrophysics Data System (ADS)

Van Daele, P.

2006-10-01

The BREAD - co-ordination action, funded by the European Commission through the Framework 6 Programme (FP6) aims at developing a multi-disciplinary approach for the realization of the 'Broadband for All' concept within Europe, bringing together societal, economic, regulatory and technological disciplines and presenting information from regional "success stories" of actual deployment. The EU objective of achieving "Broadband for All" will not be reached by solely a 'technology push' strategy but will need this multi-disciplinary approach and sharing of views and knowledge to develop new strategies and good practice recommendations in the area of 'Broadband for All'. As a co-ordination action the project wants to unite all players active in the field of the end-to-end broadband provisioning for all. It performs a multi-technological analysis of the current and evolving situation, starting from the roadmap information generated by different projects and IST instruments which focus on specific technological domains. The BREAD consortium simultaneously studies the techno-economic, societal and regulatory aspects of this "Broadband for All" concept. It tries to identify the impact of the EU regulatory framework on the successful implementation of new broadband communication services.

A generic Transcriptomics Reporting Framework (TRF) for 'omics data processing and analysis.

PubMed

Gant, Timothy W; Sauer, Ursula G; Zhang, Shu-Dong; Chorley, Brian N; Hackermüller, Jörg; Perdichizzi, Stefania; Tollefsen, Knut E; van Ravenzwaay, Ben; Yauk, Carole; Tong, Weida; Poole, Alan

2017-12-01

A generic Transcriptomics Reporting Framework (TRF) is presented that lists parameters that should be reported in 'omics studies used in a regulatory context. The TRF encompasses the processes from transcriptome profiling from data generation to a processed list of differentially expressed genes (DEGs) ready for interpretation. Included within the TRF is a reference baseline analysis (RBA) that encompasses raw data selection; data normalisation; recognition of outliers; and statistical analysis. The TRF itself does not dictate the methodology for data processing, but deals with what should be reported. Its principles are also applicable to sequencing data and other 'omics. In contrast, the RBA specifies a simple data processing and analysis methodology that is designed to provide a comparison point for other approaches and is exemplified here by a case study. By providing transparency on the steps applied during 'omics data processing and analysis, the TRF will increase confidence processing of 'omics data, and regulatory use. Applicability of the TRF is ensured by its simplicity and generality. The TRF can be applied to all types of regulatory 'omics studies, and it can be executed using different commonly available software tools. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

PubMed

McHughen, Alan; Smyth, Stuart

2008-01-01

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

Regulatory requirements and tools for environmental assessment of hazardous wastes: Understanding tribal and stakeholder concerns using Department of Energy sites

PubMed Central

Burger, Joanna; Powers, Charles; Gochfeld, Michael

2014-01-01

Many US governmental and Tribal Nation agencies, as well as state and local entities, deal with hazardous wastes within regulatory frameworks that require specific environmental assessments. In this paper we use Department of Energy (DOE) sites as examples to examine the relationship between regulatory requirements and environmental assessments for hazardous waste sites and give special attention to how assessment tools differ. We consider federal laws associated with environmental protection include the National Environmental Policy Act (NEPA), the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response Compensation and Liability Act (CERCLA), as well as regulations promulgated by the Nuclear Regulatory Commission, Tribal Nations and state agencies. These regulatory regimes require different types of environmental assessments and remedial investigations, dose assessments and contaminant pathways. The DOE case studies illustrate the following points: 1) there is often understandable confusion about what regulatory requirements apply to the site resources, and what environmental assessments are required by each, 2) the messages sent on site safety issued by different regulatory agencies are sometimes contradictory or confusing (e.g. Oak Ridge Reservation), 3) the regulatory frameworks being used to examine the same question can be different, leading to different conclusions (e.g. Brookhaven National Laboratory), 4) computer models used in support of groundwater models or risk assessments are not necessarily successful in convincing Native Americans and others that there is no possibility of risk from contaminants (e.g. Amchitka Island), 5) when given the opportunity to choose between relying on a screening risk assessments or waiting for a full site-specific analysis of contaminants in biota, the screening risk assessment option is rarely selected (e.g. Amchitka, Hanford Site), and finally, 6) there needs to be agreement on whether there has been adequate characterization to support the risk assessment (e.g. Hanford). The assessments need to be transparent and to accommodate different opinions about the relationship between characterizations and risk assessments. This paper illustrates how many of the problems at DOE sites, and potentially at other sites in the U.S. and elsewhere, derive from a lack of either understanding of, or consensus about, the regulatory process, including the timing and types of required characterizations and data in support of site characterizations and risk assessments. PMID:20719428

Gene regulatory network inference using fused LASSO on multiple data sets

PubMed Central

Omranian, Nooshin; Eloundou-Mbebi, Jeanne M. O.; Mueller-Roeber, Bernd; Nikoloski, Zoran

2016-01-01

Devising computational methods to accurately reconstruct gene regulatory networks given gene expression data is key to systems biology applications. Here we propose a method for reconstructing gene regulatory networks by simultaneous consideration of data sets from different perturbation experiments and corresponding controls. The method imposes three biologically meaningful constraints: (1) expression levels of each gene should be explained by the expression levels of a small number of transcription factor coding genes, (2) networks inferred from different data sets should be similar with respect to the type and number of regulatory interactions, and (3) relationships between genes which exhibit similar differential behavior over the considered perturbations should be favored. We demonstrate that these constraints can be transformed in a fused LASSO formulation for the proposed method. The comparative analysis on transcriptomics time-series data from prokaryotic species, Escherichia coli and Mycobacterium tuberculosis, as well as a eukaryotic species, mouse, demonstrated that the proposed method has the advantages of the most recent approaches for regulatory network inference, while obtaining better performance and assigning higher scores to the true regulatory links. The study indicates that the combination of sparse regression techniques with other biologically meaningful constraints is a promising framework for gene regulatory network reconstructions. PMID:26864687

Suborbital Safety Technical Committee- Summary of Proposed Standards & Guidelines

NASA Astrophysics Data System (ADS)

Quinn, Andy; Atencia Yepez, Amaya; Klicker, Michael; Howard, Diane; Verstraeten, Joram; Other Suborbital Safety TC Members

2013-09-01

There are currently no international safety standards and guidelines to assist designers, operators and authorities in the suborbital domain. There is a launch licensing regime in the United States (US) to assist the forerunners of the suborbital domain however this does not provide a safety approval for the vehicle against set standards or does not have an acceptable level of safety to achieve in terms of design or operation. In Europe a certification framework may be implemented however this (or any regulatory framework) is not in place as yet. This paper summarises the 5 tasks thus far completed by the International Association for the Advancement of Space Safety (IAASS) Suborbital Safety Technical Committee (SS TC) in terms of deriving standards and guidelines for the suborbital domain. The SS TC comprises members from the suborbital industry (US and European vehicle designers), safety experts, legal experts, medical/training experts, prospective spaceport operators and members from the US and European authorities (though these members cannot directly steer the standards and guidelines - they can merely review them for interest and comment on non-policy aspects). The SS TC has been divided into three working groups (WG): Regulatory WG, Technical WG and Operations WG. The 5 tasks that are summarised in this paper include: Regulatory WG - (Task 1) Clarify and promote regulatory framework for suborbital flights (including discussions on Space Law 'v' Air Law for suborbital domain); Technical WG - (Task 1) Defining & Alignment (globally) of Safety Criteria for Suborbital domain using industry best practices, (Task 2) Software/complex hardware certification for suborbital flights; Operations WG - (Task 1) Flight Crew and Spaceflight Participant Medical and Training Standards & Guidelines for suborbital flight, (Task 2) Spaceport Safety Management System. This paper also details the next set of standards and guidelines that will be derived by the SS TC. The paper concludes that these and future IAASS suborbital safety standards and guidelines are needed now and should beconsidered by the industry players before the first commercial flights expected late 2013/early 2014.

Self-Regulation in the Midst of Complexity: A Case Study of High School Physics Students Engaged in Ill-Structured Problem Solving

NASA Astrophysics Data System (ADS)

Milbourne, Jeffrey David

The purpose of this dissertation study was to explore the experiences of high school physics students who were solving complex, ill-structured problems, in an effort to better understand how self-regulatory behavior mediated the project experience. Consistent with Voss, Green, Post, and Penner's (1983) conception of an ill-structured problem in the natural sciences, the 'problems' consisted of scientific research projects that students completed under the supervision of a faculty mentor. Zimmerman and Campillo's (2003) self-regulatory framework of problem solving provided a holistic guide to data collection and analysis of this multi-case study, with five individual student cases. The study's results are explored in two manuscripts, each targeting a different audience. The first manuscript, intended for the Science Education Research community, presents a thick, rich description of the students' project experiences, consistent with a qualitative, case study analysis. Findings suggest that intrinsic interest was an important self-regulatory factor that helped motivate students throughout their project work, and that the self-regulatory cycle of forethought, performance monitoring, and self-reflection was an important component of the problem-solving process. Findings also support the application of Zimmerman and Campillo's framework to complex, ill-structured problems, particularly the cyclical nature of the framework. Finally, this study suggests that scientific research projects, with the appropriate support, can be a mechanism for improving students' selfregulatory behavior. The second manuscript, intended for Physics practitioners, combines the findings of the first manuscript with the perspectives of the primary, on-site research mentor, who has over a decade's worth of experience mentoring students doing physics research. His experience suggests that a successful research experience requires certain characteristics, including: a slow, 'on-ramp' to the research experience, space to experience productive failure, and an opportunity to enjoy the work they are doing.

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

PubMed

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.

Cloning and Characterization of 5′ Flanking Regulatory Sequences of AhLEC1B Gene from Arachis Hypogaea L.

PubMed Central

Tang, Guiying; Xu, Pingli; Liu, Wei; Liu, Zhanji; Shan, Lei

2015-01-01

LEAFY COTYLEDON1 (LEC1) is a B subunit of Nuclear Factor Y (NF-YB) transcription factor that mainly accumulates during embryo development. We cloned the 5′ flanking regulatory sequence of AhLEC1B gene, a homolog of Arabidopsis LEC1, and analyzed its regulatory elements using online software. To identify the crucial regulatory region, we generated a series of GUS expression frameworks driven by different length promoters with 5′ terminal and/or 3′ terminal deletion. We further characterized the GUS expression patterns in the transgenic Arabidopsis lines. Our results show that both the 65bp proximal promoter region and the 52bp 5′ UTR of AhLEC1B contain the key motifs required for the essential promoting activity. Moreover, AhLEC1B is preferentially expressed in the embryo and is co-regulated by binding of its upstream genes with both positive and negative corresponding cis-regulatory elements. PMID:26426444

Pharma Opportunities and Risks Multiply as Regulatory Reform Remakes APAC: Expanded Accelerated Pathways Challenge Developer Value Story, Evidence Collection, and Market Access Strategies.

PubMed

Grignolo, Alberto; Mingping, Zhang

2018-01-01

Sweeping reforms in the largest markets of the Asia-Pacific region are transforming the regulatory and commercial landscape for foreign pharmaceutical companies. Japan, South Korea, and China are leading the charge, establishing mechanisms and infrastructure that both reflect and help drive international regulatory convergence and accelerate delivery of needed, innovative products to patients. In this rapidly evolving regulatory and commercial environment, drug developers can benefit from reforms and proliferating accelerated pathway (AP) frameworks, but only with regulatory and evidence-generation strategies tailored to the region. Otherwise, they will confront significant pricing and reimbursement headwinds. Although APAC economies are at different stages of development, they share a common imperative: to balance pharmaceutical innovation with affordability. Despite the complexity of meeting these sometimes conflicting demands, companies that focus on demonstrating and delivering value for money, and that price new treatments reasonably and sustainably, can succeed both for their shareholders and the region's patient population.

NUTRIENT RESPONSE IN GREAT LAKES WETLANDS

EPA Science Inventory

The U.S. EPA National Health and Environmental Effects Laboratory's Aquatic Stressor Framework and associated Nutrient Implementation Plan define scientific and regulatory needs, and lay-out research goals too for a cross divisional program to investigate stressor-response relati...

Florida spaceports : an analysis of the regulatory framework : summary.

DOT National Transportation Integrated Search

2010-12-01

Until recently, government control : has restricted space flight to a few : highly trained persons executing : missions in the public interest : using a very limited number : of facilities and vehicles. This : environment is changing. Imaging : and c...

Corruption and air pollution in Europe.

PubMed

Ivanova, Kate

2011-01-01

This paper examines how the effectiveness of regulatory framework influences levels of sulphur emissions in a scenario where, to reduce its (emission-) tax payments, a polluting firm may under-report emissions level at the risk of being audited and fined. First, a model to explain how changes in regulatory framework (e.g., audit effectiveness) and transboundary spillovers affect both actual and reported emissions is developed. Then the theoretical predictions using data for 39 European countries from 1999 to 2003 are tested and inferences about true emission levels are made. The empirical analysis supports the theoretical predictions with significant implications for the interpretation of pollution data reported to international monitoring agencies. Countries with effective regulation are likely to have relatively high reported emissions of sulphur. But this should not automatically be interpreted as weak environmental performance, because their actual pollution levels are likely to be lower than in nations with less effective regulation.

Optimizing information flow in small genetic networks. IV. Spatial coupling

NASA Astrophysics Data System (ADS)

Sokolowski, Thomas R.; Tkačik, Gašper

2015-06-01

We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the input) by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively different regulatory strategy emerges where individual cells respond to the input in a nearly steplike fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models.

Biosimilars: The US Regulatory Framework.

PubMed

Christl, Leah A; Woodcock, Janet; Kozlowski, Steven

2017-01-14

With the passage of the Biologics Price Competition and Innovation Act of 2009, the US Food and Drug Administration established an abbreviated pathway for developing and licensing biosimilar and interchangeable biological products. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a "totality of the evidence" that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. Although questions and concerns about the biosimilars pathway remain and may slow uptake, a robust scientific program has been put in place. With three biosimilars already licensed and numerous development programs under way, clinicians can expect to see many new biosimilars come onto the US market in the coming decade. [Note added in proof: Since the writing of this article, a fourth biosimilar has been approved.].

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

PubMed Central

Siahpirani, Alireza F.

2017-01-01

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

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

PubMed

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

2014-01-01

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