Regulatory Frame Research Articles

Antiviral Defenses in Plants through Genome Editing.

Plant–virus interactions based-studies have contributed to increase our understanding on plant resistance mechanisms, providing new tools for crop improvement. In the last two decades, RNA interference, a post-transcriptional gene silencing approach, has been used to induce antiviral defenses in plants with the help of genetic engineering technologies. More recently, the new genome editing systems (GES) are revolutionizing the scope of tools available to confer virus resistance in plants. The most explored GES are zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats/Cas9 endonuclease. GES are engineered to target and introduce mutations, which can be deleterious, via double-strand breaks at specific DNA sequences by the error-prone non-homologous recombination end-joining pathway. Although GES have been engineered to target DNA, recent discoveries of GES targeting ssRNA molecules, including virus genomes, pave the way for further studies programming plant defense against RNA viruses. Most of plant virus species have an RNA genome and at least 784 species have positive ssRNA. Here, we provide a summary of the latest progress in plant antiviral defenses mediated by GES. In addition, we also discuss briefly the GES perspectives in light of the rebooted debate on genetic modified organisms (GMOs) and the current regulatory frame for agricultural products involving the use of such engineering technologies.

Thermal Comfort-CFD maps for Architectural Interior Design

Within the context of nearly Zero-Energy Buildings, it is debated that the energy-centred notion of design, proposed by regulatory frames, needs to be combined with a further focus toward users’ comfort and delight. Accordingly, the underlying theory of the research is that designers should take responsibility for understanding the heat flows through the building parts and its spaces. A design, which is sensible to the micro-thermal conditions coexisting in space, allows the inhabitants to control the building to their needs and desires: for instance, maximising the benefits of heat gain from the sun moving a series of internal partitions so as to avoid the danger of over-heating.It is thus necessary that existing simulation software tools are tested to the purpose of modelling and visualising the indoor thermal environment complexity. The research discusses how thermal comfort maps, which are prepared with the use of Computational Fluid Dynamic simulation method, could integrate energy simulation outputs to uphold qualitative architectural design decisions. Mean radiant temperature maps were thus used to design the retrofit of a small educational building in Copenhagen. The thermal opportunities of movable interior partitions (operated by the users) could be estimated, providing a new layer of information to the designer. The applicability of the thermal maps within an architectural design process is discussed adopting standard energy simulation comfort outputs as a reference. The capabilities and the limitations of the method are appraised.

Evaluation Strategy to Support the Introduction the New Cuban Conjugated Pneumococcal Vaccine in the National Health System

Objective: To present the evaluation framework supporting the clinical, epidemiological and impact studies to introduce the new Cuban conjugated pneumococcal vaccine in the national vaccination program. Methods: The design of the evaluation strategy of the new vaccine in the Cuban included: the revision of the scientific evidence available in literature, the definition of the evaluation objectives, the application of conceptual and methodological evaluation frame, the performance of the process to generate the new scientific evidences about the new vaccine. The regulatory frame for the evaluation and introduction of new PCVs were taken into consideration during the whole process. Results: The background of licensed pneumococcal vaccine with similarly based studies was synthetized. The evaluation strategy of the Cuban vaccine was presented in terms of objectives, key processes, and main components (context evaluation, generation of evidence for making-decisions, introduction of the new vaccine and impact evaluation). The procedures to collect information and analysis of the new evidence generated on PCV7-TT are defined (characterize the study problem, the functioning of the new vaccine, and cost-effectiveness and impact). The evaluation strategy is operationalized in the Cuban context, where preschool children and infants are defined as target population. The contributions, strengths and weaknesses in the evaluation design and in the generation of evidences are discussed. Conclusions: The rigorous scientific evidences generated by the implementation evaluation strategies, applied to the new Cuban conjugated pneumococcal vaccine will allow the decision-making for its introduction to national health system in Cuba.

An in silico algal toxicity model with a wide applicability potential for industrial chemicals and pharmaceuticals.

The authors modeled the 72-h algal toxicity data of hundreds of chemicals with different modes of action as a function of chemical structures. They developed mode of action-based local quantitative structure-toxicity relationship (QSTR) models for nonpolar and polar narcotics as well as a global QSTR model with a wide applicability potential for industrial chemicals and pharmaceuticals. The present study rigorously evaluated the generated models, meeting the Organisation for Economic Co-operation and Development principles of robustness, validity, and transparency. The proposed global model had a broad structural coverage for the toxicity prediction of diverse chemicals (some of which are high-production volume chemicals) with no experimental toxicity data. The global model is potentially useful for endpoint predictions, the evaluation of algal toxicity screening, and the prioritization of chemicals, as well as for the decision of further testing and the development of risk-management measures in a scientific and regulatory frame. Environ Toxicol Chem 2017;36:1012-1019. © 2016 SETAC.

‘Almost the same, but not quite’: Ontological politics of recognition in modern science fiction

This article explores how issues of ‘not quite human-ness’ expose the conditions of possibility of being considered human; of human ontology. I refer to these dynamics for identifying sameness and difference as ontological politics of recognition. Tracing the genealogies of passing, I situate passing and Othering socio-political regulation and ideological frameworks for conceptualising ontology. I am particularly concerned with how the notion of ontology is bound up in questions of race and gender, and with the entanglements of technology and biology that can destabilise apparently fixed boundaries between the (natural/normative) human and its (constructed/abnormal) Others. I identify three trajectories of passing as human in the histories of science fiction. The first trajectory discusses ontological mimicry: the ways in which the non-human attempts to be like the human. The second trajectory addresses how passing as human relies on a Butlerian performativity: doing human-ness by complying with the regulatory frames for appearances and practices. The final trajectory discusses what is at stake in contemporary ontological politics of recognition: a renegotiation of human supremacy through an emphasis on collectivity and collaboration rather that singularity and boundedness.

Adherence to tactical choices mediates regulatory fit effects in table tennis

The present work examines how regulatory fit affects table tennis performance. We find a player’s adherence to their chosen tactic (offensive vs. defensive) to be a mediator of the observed fit effects. Expert table tennis players (N = 39) were given verbal instructions (i.e. regulatory frames), before they played 6 matches each; we created baseline, fit, and non-fit conditions with each player’s chronic regulatory focus. Results replicate previously found positive effects of regulatory fit on performance. We also find evidence for a novel mediator of this effect. Players under fit were more likely to adhere to their chosen tactic, which led to higher likelihood of winning the point.

From esterilología to reproductive biology: The story of the Mexican assisted reproduction business.

This paper provides the first overview of how assisted reproduction emerged and developed in Mexico. In doing so it addresses two broad points: when and how treatments using assisted reproductive technology became common practice within reproductive medicine; and how the Mexican assisted reproduction industry emerged. The paper begins in 1949, when the first medical association dedicated to esterilología – the biomedical area focused on the study of infertility – was established, thus providing the epistemic and professional ground upon which assisted reproductive technology would later thrive. The paper then traces the way in which this biomedical industry developed, from individual doctors in their practices to networks of clinics and from a clinical practice to a reproductive industry. It also describes the different ways in which the professional community and the government have worked towards developing a regulatory frame for the practice of assisted reproduction. The paper is informed by ethnographic work conducted at clinics, conferences, online forums and websites, as well as by analysis of the contemporary national media, government documents and national medical journals from the early mid-twentieth century to the those published today.

Eu Policy and Law Regarding Railways and the Environment

For decades, railway issues were considered, in Europe, as being almost entirely in the responsibility of the Member States. This history is even reflected in the present eu approach on railway issues which has, as one of its political priorities, the objective to ensure the interoperability of national legal and technical standards all over the eu. The development of trans-European transport networks, the upcoming of high-speed transboundary trains and the internationalisation of railway freight transport which are of relative recent date, all contribute to the greater awareness of railway impacts on the environment. Policies can no longer promote railways with the argument that rail is the most environment-friendly means of transport, but are more and more obliged to take into consideration, during the planning and operation of railways, local, provincial and regional environmental concerns. The contribution passes in review the most relevant environmental concerns with regard to railways. After a short description of the regulatory frame, the different environmental aspects of railways – land use, nature conservation, noise, water, air pollution, and waste management – are discussed. Some concluding remarks follow.

Mechanism of fusidic acid inhibition of RRF- and EF-G-dependent splitting of the bacterial post-termination ribosome.

The antibiotic drug fusidic acid (FA) is commonly used in the clinic against gram-positive bacterial infections. FA targets ribosome-bound elongation factor G (EF-G), a translational GTPase that accelerates both messenger RNA (mRNA) translocation and ribosome recycling. How FA inhibits translocation was recently clarified, but FA inhibition of ribosome recycling by EF-G and ribosome recycling factor (RRF) has remained obscure. Here we use fast kinetics techniques to estimate mean times of ribosome splitting and the stoichiometry of GTP hydrolysis by EF-G at varying concentrations of FA, EF-G and RRF. These mean times together with previous data on uninhibited ribosome recycling were used to clarify the mechanism of FA inhibition of ribosome splitting. The biochemical data on FA inhibition of translocation and recycling were used to model the growth inhibitory effect of FA on bacterial populations. We conclude that FA inhibition of translocation provides the dominant cause of bacterial growth reduction, but that FA inhibition of ribosome recycling may contribute significantly to FA-induced expression of short regulatory open reading frames, like those involved in FA resistance.

Role of regulatory reforms for development and quality improvement of the construction sector in Montenegro

The authors of this paper researched the influence of the quality of the regulatory rules on the con- struction sector in Montenegro. The authors noticed and clearly pointed out that the significance of construction for, the total economy of Montenegro, its influence on other economic activities and participance in the social gross product of the country entirely justifies the need for constant attention of the politics creators. Key issues in the legal framework which negatively influenced the improve- ment of competitiveness of this sector and national economy are noticed and clearly pointed out in this paper. As the most significant, the following ones are identified: trend of provisions instability, existence of mutual collision of laws and sublegal acts, regulation of spatial planning, issuing building permits, property registration and system of public procurement. After having analyzed the changes in the regulatory frame and their affect on improving the position of Montenegro on the lists of com- petitiveness in international organizations, the authors make a general conclusion that necessity of regulatory reform with providing a predictable and functional system is one of the basic preconditions for further development of this sector.

Nutrition and Dietetic Product Shortages are A Neglected Issue in Alerting Systems and in Registries

Context: Medicines shortages have become a global phenomenon and are recognized to affect all health systems. It is a problem that has grown to become a crisis in terms of delivering patient care. Over 1400 products were reported to be in shortage in the Netherlands between 2004 and 2011. In Switzerland, in April 2016 as much as 221 products were on shortage. 44 alerts were noticed within the latest 7 days. Shortages induce individuals’ suffering, bad clinical outcomes and additional costs for public health. Objective: The aim of this review is to evaluate whether nutrition and dietetic products are a neglected issue in shortages research. Method: Eight medicines shortages reporting systems, ten batch recall registries, and homepages of manufacturers were evaluated. Categories such as food for special medical purposes and dietary use, supplements, and infant formula were included. Results: Among the products in shortage, infant formula, micronutrient additives for parenteral nutrition, vitamin and trace elements products were most frequently affected. Infant formula and potassium chloride injection concentrates are repeatedly affected by shortages as well, mainly in Germany, since 2008. Only products for parenteral nutrition, vitamins, and trace elements for oral use are registered in medicines shortage registries. Conclusion: It is highly desirable to include clinically used nutrition and dietetic products in registries. Artificial legal delimitation between food and medicines not reflecting natural commonalities impairs inclusion of nutritional products in reporting systems. It is likely that dietitians are not accus-tomed to report incidences to contribute to improved patient safety and to prevent further incidences of shortages. A rigid regulation revealed to be one of the driving forces for threat to shortage. The milder impact of the less rigid regulatory frame in food industry as compared to pharma industry is likely to facilitate an undisrupted supply chain.

CLINICAL TRANSLATION OF TISSUE ENGINEERED MEDICINAL PRODUCTS

Tissue Engineering is a rapidly growing field with novel scientific concepts, new technological methods, and evolving regulatory policies for clinical translation. Most of the current basic regulations are taken from the pharma, bio-pharma, cell therapy with little modifications, and new inclusion for development of regulatory frame work for advanced therapeutic products. We propose to highlight the important concepts in the regulatory development for tissue engineered based medicinal products (TEMPs) without any compromise on Quality, safety and efficacy. Moreover, these evolving regulations should facilitate clinical transition to help large numbers of patients on conditionally or case-by-case basis, and accelerate the submission of on-line real-time safety and efficacy parameters. This review describes general regulations and its scientific concepts; specifically in the context of clinical translation for TEMPs. Importantly, this review highlights the need of regulatory development and support for sustenance of small and medium sized organizations without any compromise on safety and efficacy of the products. Furthermore, current clinical regulatory translational challenges and opportunities to articulate risk-benefit approaches by accessing its potential strength, efficacy or availability of standard therapy, safety of new product and its relevance’s with TEMPs are discussed.

Tracing the Weaknesses of the Regulatory Framework for Clinical Trial in Nigeria

Nigeria is one of the developing countries with a very weak and incomprehensive regulatory framework for clinical trials. Past abuses of human subjects in clinical trials and cases of negligence and outright fraud necessitate the need for a stronger legal framework. An outbreak of meningitis in Nigeria in 1996 led to clinical trial of Trovan Drugs by Pfizer, which left many of the research subjects seriously impaired. Some died while some suffered paralysis and brain damage. It was obvious Nigeria has a weak regulatory frame work from the incident that took place in the mentioned above at the Infectious Dieses Hospital (IDH) Kano. Available literatures have also shown that at the time of the trial in Kano, there was no ethics committee to ensure ethics review process and monitor the ongoing trial. Objectives: This research aimed at examining the Nigerian regulatory framework to bring out its weaknesses. It will also examine the strength and weakness of the current regulatory agencies, and suggest better regulatory framework that will make Nigerians less vulnerable to manipulation and fraud in clinical trials. Methodology: Library research is used to study both primary and secondary legal resources. Finding: Lack of standard regulatory body and lack unified legal framework is the cause of failure to protect human subject in Nigeria.

A Study of the Construction of Female Identity: John Fowles’ The French Lieutenant’s Woman

The issue of identity and female consciousness as one of the major concerns of feminists has always been polemical, for there are different attitudes in formulating gender identity and consequently defining what a woman is. As its theoretical framework, this study relies on Judith Butler’s theory of gender and sexuality and studies the construction of identity in the female characters of John Fowles’ The French Lieutenant’s Woman. Judith Butler, a feminist constructivist, stresses the effect of socially constructed gender roles on creating gender identity and proposes her performative theory of gender and sexuality. In her theory Butler argues that gender is not what one is but what one does. In this sense, gender is not a stable identity from which various acts proceed; rather it is an identity constituted through a stylized repetition of normative gender roles and performances. Regarding gender as performative reveals that, what is taken as an internal essence of gender is actually fabricated through the regulatory frame of interacting discourses. It has an imitative structure which can be deconstructed. The study, thus, focuses on the effect of prescribed gender roles and norms in the process of identity formation, and examines Ernestina Freeman as a conformist character who constitutes her identity by taking on the ideal gender norms of the era and Sarah woodruff who tries to renegotiate and reenact those roles and constructs a sense of self which transcends constraints of the social and cultural hegemonic frame.

Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.

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.

A Study on Impact of Foreign Direct Investment on Gross Domestic Production in India

The review of various literatures and renowned publications is emphasizing that the gross domestic production of a nation is determined by several factors such as growth in agriculture and manufacturing sector, export, inflation, exchange rate and international investment. In spite of different factors affecting the growth, the incremental growth of foreign direct investment in various sectors is considered to be a vital factor which controls all other factor. The 1991 new economic policy has unfolded red carpet to the international investors and reduced the uncertainty on the legal and regulatory frame work boosted the investors’ confidence in the economy. As a result, the Indian economy witnessed a vigorous growth since the implementation of Liberalization, Privatization and Globalization (LPG). In this regard this paper is attempting to investigate the contribution of foreign direct investment to the gross domestic production of India. The investigation was made using a simple regression between foreign direct investment (FDI) and gross domestic production (GDP) for 23 years from 1991 – 2014. The result revealed that FDI has as positive impact on GDP.

Small Finance Banks : New Category of Differentiated Banks

In September 2015, Reserve Bank of India (RBI) announced in principle approval to ten entities for setting up yet another category of differentiated banks, named as Small Finance Banks. Eight out of ten successful candidates are already working as Micro Financing Institutions (MFIs). The primary objective of setting up of small finance banks is to further promote financial inclusion by provision of savings and credit to small business units, small and marginal farmers, and other unorganised sector entities, through high technology-low cost operations. The small finance banks will have minimum paid-up equity capital of Rs. 100 crore with minimum initial promoter's contribution of 40% of paid-up equity capital of banks and locked in for a period of five years. Unlike Payment Banks earlier announced a month ago, these banks are permitted to engage in lending activities and are subject to Reserve Bank of India's (RBI) regulatory frame work for other universal banks. The entities granted approval for setting up new banks have shown successful performance as MFIs, but will be faced with significant challenges while functioning in the new role of small finance banks with different asset and liability products but have the potential to seize the opportunity opened before them. The paper analyses various nuances of new kind of differentiated banks opened by RBI.

Seismic hazard and land management policies in Italy: the role of seismic investigation

Italy is a highly populated country with an important cultural heritage and is characterized by high seismicity. It is therefore of paramount importance to define clear and feasible policies for land management and to adopt consistent procedures for seismic risk assessment. In this context, seismic surveys aimed at providing S-wave velocity models are applied at a different degree of detail and com¬plexity. We provide a description of the regulatory frame¬work for seismic microzonation and an overview of the use of seismic measurements, with particular regard to surface wave analysis, for different levels of microzoning with some examples of recent applications in Italy. The definition of cost-effective strategies for seismic risk reduction requires a detailed knowledge of seismic hazard. Seismic microzonation can help in orienting the limited available funds for retrofitting to most the critical situations, developing city-planning activities aiming at reducing expo¬sure to earthquakes and exploitation of the most hazardous areas. In general, central authorities provide reference seismic hazard estimates at a national scale (e.g., for Italy, see Stucchi et al., 2011). However, local evaluations are required to account for the effects of seismo-stratigraphic and geomor¬phological site conditions on the expected seismic ground motion. These effects may play a dramatic role in enhancing local damages, as for example the local instabilities induced by ground shaking (liquefaction, induced landslides), or those resulting from interference of seismic waves induced by the presence of heterogeneities in the subsoil (e.g., Tertulliani et al., 2012).

A Global Health Diagnostic for Personalized Medicine in Resource-Constrained World Settings: A Simple PCR-RFLP Method for Genotyping CYP2B6 g.15582C>T and Science and Policy Relevance for Optimal Use of Antiretroviral Drug Efavirenz.

The use of pharmacogenomics (PGx) knowledge in treatment of individual patients is becoming a common phenomenon in the developed world. However, poorly resourced countries have thus far been constrained for three main reasons. First, the cost of whole genome sequencing is still considerably high in comparison to other (non-genomics) diagnostics in the developing world where both science and social dynamics create a dynamic and fragile healthcare ecosystem. Second, studies correlating genomic differences with drug pharmacokinetics and pharmacodynamics have not been consistent, and more importantly, often not indexed to impact on societal end-points, beyond clinical practice. Third, ethics regulatory frames over PGx testing require improvements based on nested accountability systems and in ways that address the user community needs. Thus, CYP2B6 is a crucial enzyme in the metabolism of antiretroviral drugs, efavirenz and nevirapine. More than 40 genetic variants have been reported, but only a few contribute to differences in plasma EFV and NVP concentrations. The most widely reported CYP2B6 variants affecting plasma drug levels include c.516G>T, c.983T>C, and to a lesser extent, g.15582C>T, which should be considered in future PGx tests. While the first two variants are easily characterized, the g.15582C>T detection has been performed primarily by sequencing, which is costly, labor intensive, and requires access to barely available expertise in the developing world. We report here on a simple, practical PCR-RFLP method with vast potentials for use in resource-constrained world regions to detect the g.15582C>T variation among South African and Cameroonian persons. The effects of CYP2B6 g.15582C>T on plasma EFV concentration were further evaluated among HIV/AIDS patients. We report no differences in the frequency of the g.15582T variant between the South African (0.08) and Cameroonian (0.06) groups, which are significantly lower than reported in Asians (0.39) and Caucasians (0.31). The g.15582C/T and T/T genotypes were associated with significantly reduced EFV levels (p=0.006). This article additionally presents the policy relevance of the PGX global health diagnostics and therefore, collectively makes an original interdisciplinary contribution to the field of integrative biology and personalized medicine in developing world. Such studies are, in fact, broadly important because resource-constrained regions exist not only in developing world but also in major geographical parts of the G20 nations and the developed countries.

Coordination Under Uncertain Conditions: An Analysis of the Fukushima Catastrophe

This paper analyzes the impacts of the 11 March 2011 earthquake and tsunami at the Fukushima nuclear power plant in Japan, which were amplified by a failure of coordination across the plant, corporate, industrial, and regulatory levels, resulting in a nuclear catastrophe, comparable in cost to Chernobyl. It derives generic lessons for industrial structure and regulatory frame of the electric power industry by identifying the two shortcomings of a horizontal coordination mechanism: instability under large shock and the lack of “defense in depth.”