Regulatory Knowledge Research Articles

Combining computer vision with semantic reasoning for on-site safety management in construction

Computer vision has been utilized to extract safety-related information from images with the advancement of video monitoring systems and deep learning algorithms. However, construction safety management is a knowledge-intensive task; for instance, safety managers rely on safety regulations and their prior knowledge during a jobsite safety inspection. This paper presents a conceptual framework that combines computer vision and ontology techniques to facilitate the management of safety by semantically reasoning hazards and corresponding mitigations. Specifically, computer vision is used to detect visual information from on-site photos while the safety regulatory knowledge is formally represented by ontology and semantic web rule language (SWRL) rules. Hazards and corresponding mitigations can be inferred by comparing extracted visual information from construction images with pre-defined SWRL rules. Finally, the example of falls from height is selected to validate the theoretical and technical feasibility of the developed conceptual framework. Results show that the proposed framework operates similar to the thinking model of safety managers and can facilitate on-site hazard identification and prevention by semantically reasoning hazards from images and listing corresponding mitigations.

LncRNA HAND2-AS1 exerts anti-oncogenic effects on bladder cancer via restoration of RARB as a sponge of microRNA-146

BackgroundGrowing evidence has shown that long noncoding RNA: microRNA: mRNA is implicated in tumor initiation, development, and progression. Long noncoding RNA HAND2-AS1 exhibits anti-cancer effects in diverse cancers. However, the knowledge of HAND-AS1 in bladder cancer development remains unknown.MethodsLncRNA and miRNA microarray was conducted to explore different expressed RNA in primary bladder cancer specimens. RNA-RNA interaction prediction tools miRcode (http://www.mircode.org/), DIANA-lncBase v2 (https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=lncbasev2%2Findex-experimental), DIANA-TarBase v.8 (https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=tarbasev8%2Findex) and miRDB (http://www.mirdb.org/) were employed to predict the interactions between RNA. Bladder cancer cell lines were used to perform cell proliferation and apoptosis assays. Western blot and quantitative Real-time Polymerase Chain Reaction were used to determine the expression of protein and RNA separately. Dual-luciferase assay was conducted to determine the activity of three prime untranslated region of retinoic acid receptor beta (RARB). Furthermore, 5637 human bladder cancer mouse models were established to investigate the interactions of lncRNA: miRNA: mRNA in vivo.ResultsBased on the RT2 lncRNA PCR Arrays analysis, we validated HAND2-AS1 declined in bladder cancer and negatively correlated with the depth of invasion and grades. The overexpression of HAND2-AS1 in human bladder cancer cells 5637 and RT4 hampered cell proliferation by provoking Caspase 3-triggered cell apoptosis. Besides, one of the HAND2-AS1 sponges, miR-146, elevated in bladder cancer and targeted the tumor suppressor, retinoic acid receptor beta (RARB). We further demonstrated that the HAND2-AS1: miR-146: RARB complex promoted Caspase 3-mediated apoptosis by suppressing COX-2 expression. Finally, the results gained in mouse xenografts suggested that HAND2-AS1 diminished miR-146 expression, thereby reversing the suppression of miR-146 on RARB-mediated apoptosis and contributing to bladder cancer regression.ConclusionThe present study sheds light on the fact that lncRNA HAND2-AS1 exerted as a tumor suppressor by releasing RARB from miR-146, leading to tumor proliferation and invasion inhibition. The findings expanded HAND2-AS-mediated regulatory networks' knowledge and provided novel insights to improve the RARB-targeted regimens against bladder cancer.

Underground space, the legal governance of a critical resource in circular economy

During the last two decades the enhanced multiple use of underground resources and space led to a growing number of issues which the current European Union (EU) and/or its Member States (MS) national legal and regulatory frameworks and knowledge bases are not able to manage efficiently, from a sustainable development perspective. With a focus on Europe, this study is a horizon scanning review to raise awareness on this situation and highlight new need for governance solutions which may fit diverse legal and authority settings in the different jurisdictions, and support the transition towards a more circular economy, decoupling subsurface resources and space use from the negative impacts this use frequently causes. It involves the legal acknowledgement of underground resources and space as mostly finite resources. The identification of resources owners, the conflicting interests of the multiple stakeholders, the clear designation of the physical conditions and dynamics related to each resource category, the interactions between subsurface and surface resources are making the regulation, planning and use of subsurface natural resources a complex, but necessary task for public authorities. Establishing a harmonized public authority scheme of permitting and sustainable resource management, supported by the development of a 3D (and 4D) information and resource classification system should be a priority for the EU and its MS. The preliminary results and legal analogues indicate that underground space utilization can also be assessed in the criticality context.

Regulatory Standards in Orphan Medicinal Product Designation in the EU.

Twenty years of orphan regulation in Europe have now elapsed, with almost 2,400 orphan designated medicinal products and more than 190 orphan products authorised in the EU. Alongside the evolution in understanding of rare diseases, considerable regulatory knowledge has also been accumulated regarding the level of evidence that would support inclusion of products into the framework. This article reviews publications and regulatory documents pertaining to orphan medicinal product designation in the EU and discusses the general expectations in submitted applications as reflected in the current regulatory practise. Important elements to recommend granting a European orphan designation are the key considerations of orphan condition, medical plausibility, seriousness, and prevalence, while significant benefit is also assessed when there are authorised medicinal products for the sought indication. This review attempts to clarify the specific concepts currently used in that regard and discusses how the available data can be used to justify the criteria for designation. Moving away from theoretical expectations or assumptions, it stresses that the applications have to be complemented with nosological and epidemiological justifications pertaining to the proposed condition, as well as relevant data in specific non-clinical in vivo models or in affected patients to support inclusion into the orphan scheme.

An Integrated Database of Small RNAs and Their Interplay With Transcriptional Gene Regulatory Networks in Corynebacteria.

Small RNAs (sRNAs) are one of the key players in the post-transcriptional regulation of bacterial gene expression. These molecules, together with transcription factors, form regulatory networks and greatly influence the bacterial regulatory landscape. Little is known concerning sRNAs and their influence on the regulatory machinery in the genus Corynebacterium, despite its medical, veterinary and biotechnological importance. Here, we expand corynebacterial regulatory knowledge by integrating sRNAs and their regulatory interactions into the transcriptional regulatory networks of six corynebacterial species, covering four human and animal pathogens, and integrate this data into the CoryneRegNet database. To this end, we predicted sRNAs to regulate 754 genes, including 206 transcription factors, in corynebacterial gene regulatory networks. Amongst them, the sRNA Cd-NCTC13129-sRNA-2 is predicted to directly regulate ydfH, which indirectly regulates 66 genes, including the global regulator glxR in C. diphtheriae. All of the sRNA-enriched regulatory networks of the genus Corynebacterium have been made publicly available in the newest release of CoryneRegNet(www.exbio.wzw.tum.de/coryneregnet/) to aid in providing valuable insights and to guide future experiments.

NIAID ClinRegs-a Public Database of Country Clinical Research Regulatory and Ethics Requirements: Design and Utilization Analysis.

Regulatory compliance is challenging for multinational clinical trials. Conflicts between country requirements impedes research and slows the approval of medicines, leading the pharmaceutical industry to devote significant resources to this area. Many academic centers and nonprofits cannot support industry-level investment and are vulnerable to noncompliance. To address an insufficiency in public access to this information, the National Institute of Allergy and Infectious Diseases developed ClinRegs-a public access database of clinical research regulations. This report describes ClinRegs' features, maintenance, and usage. From September 2019 through August 2020, ClinRegs had 68 504 users, 60% from outside the United States, demonstrating the demand for accessible, reliable, country-specific regulatory information. Tools such as ClinRegs can help increase regulatory compliance and free up resources for research. We encourage our partner agencies and biomedical research industries to promote greater regulatory knowledge sharing and harmonization for the betterment of clinical research and improved public health.

To Test or Not to Test: Tools, Rules, and Corporate Data in US Chemicals Regulation

When the Toxic Substances Control Act (TSCA) was passed by the US Congress in 1976, its advocates pointed to new generation of genotoxicity tests as a way to systematically screen chemicals for carcinogenicity. However, in the end, TSCA did not require any new testing of commercial chemicals, including these rapid laboratory screens. In addition, although the Environmental Protection Agency was to make public data about the health effects of industrial chemicals, companies routinely used the agency’s obligation to protect confidential business information to prevent such disclosures. This paper traces the contested history of TSCA and its provisions for testing, from the circulation of the first draft bill in the Nixon administration through the debates over its implementation, which stretched into the Reagan administration. The paucity of publicly available health and environmental data concerning chemicals, I argue, was a by-product of the law and its execution, leading to a situation of institutionalized ignorance, the underside of regulatory knowledge.

Uncovering opportunities for effective species conservation banking requires navigating technical and practical complexities

AbstractIn the USA, Species Conservation Banking is a prominent example of compensatory biodiversity impact mitigation, with an annual market value estimated at US$354.2 million. Species Conservation Banking represents a useful case study of a well‐established program that can provide empirical insights into the practicalities of implementing quantitative compensatory biodiversity mitigation on‐the‐ground. Using semi‐structured key‐informant interviews structured around well‐established technical challenges to compensatory mitigation, this study aimed to understand (i) how and why these challenges are or are not addressed in practice; and (ii) how these challenges relate to practical challenges faced by conservation banking stakeholders on‐the‐ground. Challenges identified included: (i) defining trading currencies and equivalence, (ii) regulatory and political uncertainty, (iii) regulatory agency capacity, will and knowledge, (iv) lack of policies, standards, and competition with other mitigation mechanisms, (v) long‐term uncertainty/longevity, and (vi) lack of species knowledge and data transparency. These challenges are numerous, diverse, interlinked and transdisciplinary, and collectively inhibit the ability of practitioners to resolve underlying technical challenges—a finding likely applicable to related biodiversity offset programs. To help address challenges and navigate this complexity, we formulate several recommendations for conservation banking stakeholders to improve the chances of beneficial biodiversity outcomes being achieved.

A pharmacist-driven Food and Drug Administration incident surveillance and response program for compounded drugs.

DisclaimerIn an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.PurposeTo provide an overview of compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, and to describe the pharmacist’s role within the US Food and Drug Administration’s (FDA’s) Compounding Incidents Program, whose efforts are aimed at protecting the public against poor-quality compounded drugs through surveillance, review and response to adverse events and complaints.SummaryCompounded drugs may serve an important medical need for patients who cannot be treated with medications approved by FDA; however, compounded drugs are not approved by FDA and are not subject to premarket review for safety, efficacy, or manufacturing quality; thus, they may pose safety risks to patients. Prompt reporting of adverse events or complaints related to compounding is important in identifying these risks and implementing safeguards to protect the public. FDA’s Compounding Incidents Program consists of a team of pharmacists dedicated to the surveillance and review of adverse events and complaints and follow-up actions related to safety risks associated with compounded drugs. Pharmacists are a vital component of FDA’s Compounding Incidents Program, utilizing their clinical skill set and regulatory knowledge to review and act on safety issues that affect public health.ConclusionAs FDA continues to expand the Compounding Incidents Program and its efforts to protect the public against poor-quality compounded drugs, we encourage the continued submission of adverse event reports by healthcare professionals and consumers to FDA’s MedWatch reporting system in addition to adverse event reporting compliance by outsourcing facilities.

Innovation and adaptation to climate change: Evidence from the water sector in Africa

Africa is predicted to be the region most affected by climate change and water is one of the sectors with anticipated severe impacts. Innovations in this sector are being promoted as part of the adaptation solutions to this problem. In this paper, we use available data on water-related climate change adaptation technological developments to examine the degree to which the vulnerability to climate change in the water sector is motivating these innovations. Using pooled data for African countries between 1990 and 2016, we estimate the relationship between climate-induced vulnerability in the water sector and water-related innovations, controlling for country size and proxies for technology transfer environment, institutional and regulatory quality, knowledge base, and research and development activity. Data on innovative activity shows evidence of over-dispersion; thus we use the negative binomial distribution with robust standard errors for estimation of our model. We find evidence that countries most exposed to water stress are innovating at lower rates. Though counterintuitive, this result is explained by the fact that such vulnerable countries also tend to have little research and development infrastructure needed to develop the kind of high quality innovations that usually necessitate patenting. Our result suggests that African countries experiencing water stress may need to reconsider priorities in the design of water-related adaptation to climate change. We also find that a country’s knowledge base and openness to trade are important determinants of adaptation technologies in the water sector.

The science behind the ban: the outstanding impact of ecotoxicological research on the regulation of neonicotinoids.

The restrictions and bans imposed on insecticides of the neonicotinoid family in Europe were legitimized by emerging knowledge about their impact on the health of bee populations. That such knowledge was articulated and acted upon in the regulatory space is puzzling, given the standard forms of regulatory science, and the ways in which scientific knowledge is used in this very space. This short article reviews research in social science about regulation and regulatory knowledge, to help understand how research on bee decline opened the possibility of wide regulatory restrictions on neonicotinoids.

Carbon catabolite regulation of secondary metabolite formation, an old but not well-established regulatory system.

SummarySecondary microbial metabolites have various functions for the producer microorganisms, which allow them to interact and survive in adverse environments. In addition to these functions, other biological activities may have clinical relevance, as diverse as antimicrobial, anticancer and hypocholesterolaemic effects. These metabolites are usually formed during the idiophase of growth and have a wide diversity in their chemical structures. Their synthesis is under the impact of the type and concentration of the culture media nutrients. Some of the molecular mechanisms that affect the synthesis of secondary metabolites in bacteria (Gram‐positive and negative) and fungi are partially known. Moreover, all microorganisms have their peculiarities in the control mechanisms of carbon sources, even those belonging to the same genus. This regulatory knowledge is necessary to establish culture conditions and manipulation methods for genetic improvement and product fermentation. As the carbon source is one of the essential nutritional factors for antibiotic production, its study has been imperative both at the industrial and research levels. This review aims to draw the utmost recent advances performed to clarify the molecular mechanisms of the negative effect exerted by the carbon source on the secondary metabolite formation, emphasizing those found in Streptomyces, one of the genera most profitable antibiotic producers.

81007 Training Biomedical Engineers in Regulatory Science: Critical Role of Experts from Industry and FDA

ABSTRACT IMPACT: Lack of regulatory knowledge and education is a key barrier to the translation of medical devices and we describe the design and results for a university graduate-level course providing training on medical device regulatory submissions for approval that can help fill this unmet need and improve and accelerate translational success. OBJECTIVES/GOALS: Within the Indiana CTSI, the Medical Technology Advance Program (MTAP) in the Purdue University Weldon School of Biomedical Engineering (BME) offers three courses in regulatory science and regulatory affairs for medical devices. One course is focused on regulatory submissions for approval, and this report details the course design and evaluation. METHODS/STUDY POPULATION: For Fall 2020, the Regulatory Submissions for Approval course was enhanced to increase participation from regulatory professionals in US FDA and industry, with the core content, curriculum and course design led by BME faculty. The course was taught two days per week and included both in-person and remote (synchronous or asynchronous) attendance options. During the first class session each week a topic was covered in standard lecture format by BME faculty with industry regulatory experience. During the second class session, guests from both industry and FDA were invited to provide in-depth discussion on the topic, share perspectives and viewpoints, present real-world examples, experiences, and case studies, and answer student questions. An end of semester survey evaluated the effectiveness of the course design. RESULTS/ANTICIPATED RESULTS: Medical Device regulatory submissions and related activities were taught including product classification, presubmissions and meetings, 510(k), de novo, EUA, PMA, HDE, and advisory panels. FDA history, regulatory careers, regulatory science, and EU, China, and Japan regulations were also discussed. Overall, 29 speakers from FDA and industry participated live via video calls. A survey completed by 21/23 studentsrevealed overall satisfaction: all reported increased regulatory understanding and 20/21 learned ‘a lot’ or ‘an incredible amount’. The weekly lecture was the top factor contributing to learning, and guest speakers were the next most important factors. Nearly all students indicated FDA and industry speakers were ‘very’ or ‘extremely’ valuable/helpful. Additional results will be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: The three courses are designed to improve medical device translation by training students to better understand regulatory processes and pathways. Survey results and feedback indicated this course was successful. Continued participation from FDA and industry is critical to the learning. Additional case studies will also help enhance learning.

NANOTECNOLOGIA: QUESTÕES LEGAIS E ÉTICA NA EUROPA

Nanotechnology is a very vast field which includes a range of technologies at the nano scale, such as pharmaceuticals, biotechnology, genomics, neuroscience, robotics and information technologies. Nanotechnology is the latest technological innovation in global debates on risk regulation and international cooperation. Regulatory bodies have started dealing with the potential risks posed by nanoparticles. Since 2004 the European Union has been developing a regulatory policy to tighten control and to improve regulatory adequacy and knowledge of nanotechnology risks. Currently, specific provisions on nanomaterials have been introduced for biocides, cosmetics, food additives, food labelling and materials in contact with foodstuff. The statement that nanotechnologies do inevitably imply ethical questions. The main problems are public trust, potential risks, issues of environmental impact, transparency of information, responsible nanosciences and nanotechnologies research. The aim of this article is to analysis the main problems regulating nanotechnology and some aspects of ethics.

Intelligent decision support method in a typical situation

The article discusses a decision support method using a knowledge base. The relevance of the study of issues related to decision-making in typical situations is shown. In order to increase the effectiveness of management activities, the issues of system integration of the regulatory framework, ontological model and knowledge base of the intelligent subsystem of decision support within the framework of the business process are considered. In support of the proposed method, a model has been formed for replenishing the knowledge base both at the structural and analytical levels, which demonstrates the connection between the most important elements of the system: the ontological model, the knowledge base and the normative subsystem. An example of using the proposed scheme is shown. To demonstrate the model of functioning of the decision support system, an algorithm for replenishing the knowledge base is proposed and described. As a conceptual basis for the formal description of the model, operations for working with knowledge are described in the set-theoretic aspect. The principles of adaptation of the ontological model as an information object for linking with the knowledge base are considered. The conceptual diagram of the general structure of the ontological model for making decisions within the framework of the business process as a set of interrelated concepts is proposed and demonstrated. An information model of a specialized database has been developed and presented, serving as a technical basis for building a knowledge base of a decision support system in a typical situation, its main structural elements, the principles of their interrelation and an approach to ensuring the consistency of its internal structure are described.

Role of CTSA institutes and academic medical centers in facilitating preapproval access to investigational agents and devices during the COVID-19 pandemic.

With no approved treatments for COVID-19 initially available, the Food and Drug Administration utilized multiple preapproval pathways to provide access to investigational agents and/or medical devices: Expanded Access, Emergency Use Authorizations, and Clinical Trials. Regulatory units within an Academic Medical Center (AMC), including those part of the Clinical and Translational Science Award (CTSA) consortium, have provided support for clinicians in navigating these options prior to the pandemic. As such, they were positioned to be a resource for accessing therapies during the COVID-19 public health emergency. A small survey and a follow-on poll of the national Investigational New Drug (IND)/Investigational Device Exemption (IDE) Workgroup were conducted in October and December 2020 to determine whether CTSA regulatory units assisted in facilitating access to COVID-19 therapies and the extent of pandemic-related challenges these units faced. Fifteen survey and 21 poll responses were received, which provided insights into the demands placed on these regulatory support units due to the pandemic and the changes required to provide critical support during this and future crises. Key changes and lessons learned included the importance of regulatory knowledge to support the institutional response, the critical need for electronic submission capacity for Food and Drug Administration (FDA) documents, and the nimble reallocation of regulatory and legal resources to support patient access to investigational agents and/or medical devices during the pandemic. AMC- and CTSA-based regulatory units played a meaningful role in the COVID-19 pandemic but further unit modifications are needed for enabling more robust regulatory support in the future.

Pengaruh Pengetahuan Peraturan, Komitmen Manajemen, Dan Lingkungan Birokrasi Terhadap Penyerapan Anggaran Terkait Pengadaan Barang/Jasa

This study aims to determine the effect of regulatory knowledge, management commitment, and the bureaucratic environment on budget absorption related to the procurement of goods / services in the government of Padang City. A sample of 82 respondents was determined by using a total sampling technique consisting of heads of fields or staff of the procurement department. Data were analyzed using multiple regression formulas with the help of the SPSS application. This study concludes that regulatory knowledge does not affect budget absorption related to goods / services procurement. Management commitment has a positive and significant effect on budget absorption related to the procurement of goods / services. Meanwhile, the bureaucratic environment has no effect on budget absorption related to the procurement of goods / services

Strengthening regulatory science in academia: STARS, an EU initiative to bridge the translational gap

Truly disruptive medicine innovation and new treatment paradigms tend to start in non-commercial research institutions. However, the lack of mutual understanding between medicine developers and regulators when it comes to medicine development significantly delays or even prevents the access of patients to these innovations. Here, we outline what regulatory-related barriers hamper the translational development of novel products or new treatment paradigms initiated in academia, and propose key steps towards improved regulatory dialogue among academia, funding bodies and regulatory authorities. Moreover, we briefly describe how the STARS (Strengthening Training of Academia in Regulatory Science) project aims to reach out to medicine innovators in academia to bridge the regulatory knowledge gap and enhance this dialogue to facilitate the implementation of academic research findings in clinical practice.

Exploring the Relationship between Fishing Regulations and Angler Compliance in Virginia

Fishing regulations are often complex and reliant upon a general understanding of geographical awareness. Fishing regulations for the same fish species can vary across neighboring waterways or along a single waterway that is delineated into a river and lake, for example. It is plausible that anglers may not understand these complex regulations and subsequently may act in non-compliance. The purpose of this study was to explore the relationship between fishing regulations and angler compliance on the New River and Claytor Lake in Virginia. A survey was used to collect data from a sample of 15,000 registered Virginia freshwater anglers from July 2016-September 2017. Both anglers’ regulatory knowledge and several demographic variables were used to predict the likelihood of anglers’ compliance using a regression analysis. The potential policy implications of this research may include an increase in attention for angler education programs and discretionary tactics by law enforcement.

Assessment of Flow through Microchannels for Inertia-Based Sorting: Steps toward Microfluidic Medical Devices.

The development of new standardized test methods would allow for the consistent evaluation of microfluidic medical devices and enable high-quality products to reach the market faster. A comprehensive flow characterization study was conducted to identify regulatory knowledge gaps using a generic inertia-based spiral channel model for particle sorting and facilitate standards development in the microfluidics community. Testing was performed using 2–20 µm rigid particles to represent blood elements and flow rates of 200–5000 µL/min to assess the effects of flow-related factors on overall system performance. Two channel designs were studied to determine the variability associated with using the same microchannel multiple times (coefficient of variation (CV) of 27% for Design 1 and 18% for Design 2, respectively). The impact of commonly occurring failure modes on device performance was also investigated by simulating progressive and complete channel outlet blockages. The pressure increased by 10–250% of the normal channel pressure depending on the extent of the blockage. Lastly, two common data analysis approaches were compared—imaging and particle counting. Both approaches were similar in terms of their sensitivity and consistency. Continued research is needed to develop standardized test methods for microfluidic systems, which will improve medical device performance testing and drive innovation in the biomedical field.