High‐throughput genomic technologies are revolutionizing human genetics. So far the focus has been on the 1.5% of the genome, which is coding, in spite of the fact that the great majority of genomic variants fall outside the coding regions. Recent efforts to annotate the non‐coding sequence show that over 80% of the genome is biochemically active. The genome is divided into regulatory domains consisting of sequence regions that enhance and/or silence the expression of nearby genes and are, in some (...) cases, separated by boundaries with insulator activity. In this paper, we review the recent advances in the identification of variations that influence gene regulation and their consequences for human disease. We hypothesize that structural variations outside of the coding genome can interfere with normal gene regulation by disrupting the regulatory landscape. Therefore, the regulatory landscape of the genome has also to be taken into consideration when investigating the pathology of human disease. (shrink)

Precise spatiotemporal control of gene expression during normal development and cell differentiation is achieved by the combined action of proximal (promoters) and distal (enhancers) cis‐regulatory elements. Recent studies have reported that a subset of promoters, termed Epromoters, works also as enhancers to regulate distal genes. This new paradigm opened novel questions regarding the complexity of our genome and raises the possibility that genetic variation within Epromoters has pleiotropic effects on various physiological and pathological traits by differentially impacting multiple proximal (...) and distal genes. Here, we discuss the different observations pointing to an important role of Epromoters in the regulatory landscape and summarize the evidence supporting a pleiotropic impact of these elements in disease. We further hypothesize that Epromoter might represent a major contributor to phenotypic variation and disease. (shrink)

On June 5, 2024, the Australian Capital Territory passed a law to permit voluntary assisted dying (“VAD”). The Australian Capital Territory became the first Australian jurisdiction to permit nurse practitioners to assess eligibility for VAD. Given evidence of access barriers to VAD in Australia, including difficulty finding a doctor willing to assist, the Australian Capital Territory’s approach should prompt consideration of whether the role of nurses in VAD should be expanded in other Australian jurisdictions. Drawing on lessons from Canada, which (...) currently permits nurse practitioners to assess patient eligibility, we argue that the time has come for Australian jurisdictions to expand the role of nurses in VAD systems. This would be an important step in ensuring access to VAD for patients in practice. Attention, however, must also be paid to ensuring adequate remuneration of nurses (and doctors) if this goal of promoting access is to be achieved in practice. (shrink)

Transposable elements are no longer considered to be “junk” DNA. Here, we review how TEs can impact gene regulation systematically. TEs encode various regulatory elements that enables them to regulate gene expression. RJ Britten and EH Davidson hypothesized that TEs can integrate the function of various transcriptional regulators into gene regulatory networks. Uniquely TEs can deposit regulatory sites across the genome when they transpose, and thereby bring multiple genes under control of the same regulatory logic. Several (...) studies together have robustly established that TEs participate in embryonic development and oncogenesis. We discuss the regulatory characteristics of TEs in context of evolution to understand the extent of their impact on gene networks. Understanding these features of TEs is central to future investigations of TEs in cellular processes and phenotypic presentations, which are applicable to development and disease studies. We re-visit the Britten–Davidson “gene-battery” model and understand the genetic and transcriptional impact of TEs in innovating gene regulatory networks. Transposable elements are exogenous sequences that have either been co-opted or repurposed for host functions. The vast amounts of TE sequence in the genome provides raw material for gene expression regulation, and still remains to be fully understood; the “gene-battery” model provides the basis for understanding this. (shrink)

We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long‐range transcriptional regulation. Several observations suggest that TADs can (...) indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied. (shrink)

Two major regulatory changes are affecting the provision of undergraduate legal education in England and Wales. On the one hand, the Qualifying Law Degree is being deregulated, meaning law schools are free to make significant changes to how and what they teach. On the other hand, higher education in England has seen a significant overhaul through the creation of the Office for Students, which treats students as consumers. Now more than ever, law schools need to ask themselves existential questions (...) which will not only test their continued relevance or indeed viability within the ‘market’ for higher education, but also the status of the discipline of law as a whole. The regulatory landscape may indeed present a significant threat, but it is also an opportunity to reflect on what law schools are for, and consequently what changes could result from the academic freedom that comes with deregulation. Whilst different law schools will interpret their mission differently, they should caution against either generalised inertia or succumbing to an outcomes-oriented provision that simply prepares students for the new Solicitors Qualifying Examination. Instead, law schools will find their proper purpose in critical reflection and academic self-grounding, providing undergraduate students with a ‘question everything’ mentality, and showing them that law is something to be experienced and not merely learnt. (shrink)

Approaches to induce tumor differentiation often result in manageable and therapy‐naïve cellular states in cancer cells. This transformation is achieved by activating pathways that drive tumor cells away from plasticity, a state that commonly correlates with enhanced aggression, metastasis and resistance to therapy. Here, we discuss signaling pathways, epigenetics and non‐coding RNAs as three main regulatory levels with the potential to drive tumor differentiation and hence as potential targets in differentiation therapy approaches. The success of an effective therapeutic regimen (...) in one cancer, however, does not necessarily sustain across cancer types; a phenomenon largely resulting from heterogeneity in the genetic and physiological landscapes of tumor types necessitating an approach designed for each cancer's unique genetic and phenotypic build‐up. (shrink)

It is now more than a decade since the release of the Royal Society and Royal Academy of Engineering’s seminal report on nanosciences and nanotechnologies. The report, for the first time, brought together the spectrum of scientific and societal issues underpinning the emergence of the technology. In articulating 21 recommendations, the RA/RAEng provided the United Kingdom Government—and others—with an agenda on how they could, and should, deal with the disparate aspects of the technology. The report provides a baseline to measure (...) progress against. By focusing on the eight recommendations that dealt specifically with regulation and governance, I reflect on the extent, and nature, of this progress; identify key actors in shaping the evolving governance framework; and, importantly, distinguish areas where progress appears to have lagged. (shrink)

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

With the ongoing coronavirus disease 2019 pandemic, technological, socio-political, and institutional changes have led to a “new normal” competitive landscape, firms must make longer-term strategic changes to deal with short-term discontinuities and great uncertainties to acquire sustainable advantage. Based on regulatory focus theory and upper echelons theory, this study explores the relationship between CEO regulatory focus and corporate strategic change and examines the moderating effects of analysts’ optimism bias in earning forecasts. The study uses data from A-share-listed companies (...) in China during 2010–2018. We find that CEO promotion focus is positively associated with strategic change, while CEO prevention focus is negatively associated with strategic change. We also find analysts’ optimism bias in earning forecasts would moderate these relationships. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate the non‐linear, (...) stochastic dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

The prevalence of technology-embedded products, services, and cities, described colloquially as ‘smart’ technologies and ‘smart’ cities, has seen a spate of unprecedented growth in recent years. South Africa (SA) has not been left behind, with smartphones, smart watches, and smart voice-controlled virtual personal assistants such as Amazon’s Alexa now frequently used. But while these technologies hold great promise to revolutionise homes, offices and cities, their adoption poses challenges to individual and collective interests and wellbeing. After demonstrating the legal and ethical (...) difficulties brought about by the introduction of these technologies, this article explores whether SA legislation is sufficiently robust to address these challenges. While the current legislative landscape addresses certain crucial difficulties – such as the safeguarding of personal data by the Protection of Personal Information Act No. 4 of 2013 (‘POPIA’) – it is suggested that the position regulating other aspects of smart technology adoption is, in large part, fragmented and ill-equipped to deal with some of the more pressing legal and ethical questions. Our contention is that, not dissimilar to the issues arising from artificial intelligence-based technological adoption, the extant legislative and regulatory frameworks do not go far enough in addressing the many concerns emerging from recent novel technological design, development, and deployment. Not only do smart technologies give rise to unique challenges, so does their deployment within the Global South and in South Africa, in particular. We suggest that appropriate and effective regulatory reform measures be undertaken in SA to provide better ethical guidance and policy prescriptions buttressed by rigorous regulatory oversight. (shrink)

Nowadays, Artificial Intelligence (AI) is present in all sectors of the economy. Consequently, both data-the raw material used to build AI systems- and AI have an unprecedented impact on society and there is a need to ensure that they work for its benefit. For this reason, the European Union has put data and trustworthy AI at the center of recent legislative initiatives. An important element in these regulations is transparency, understood as the provision of information to relevant stakeholders to support (...) their understanding of AI systems and data throughout their lifecycle. In recent years, an increasing number of approaches for documenting AI and datasets have emerged, both within academia and the private sector. In this work, we identify the 36 most relevant ones from more than 2200 papers related to trustworthy AI. We assess their relevance from the angle of European regulatory objectives, their coverage of AI technologies and economic sectors, and their suitability to address the specific needs of multiple stakeholders. Finally, we discuss the main documentation gaps found, including the need to better address data innovation practices (e.g. data sharing, data reuse) and large-scale algorithmic systems (e.g. those used in online platforms), and to widen the focus from algorithms and data to AI systems as a whole. (shrink)

In _ Plato's Camera_, eminent philosopher Paul Churchland offers a novel account of how the brain constructs a representation -- or "takes a picture" -- of the universe's timeless categorical and dynamical structure. This construction process, which begins at birth, yields the enduring background conceptual framework with which we will interpret our sensory experience for the rest of our lives. But, as even Plato knew, to make singular perceptual judgments requires that we possess an antecedent framework of abstract categories to (...) which any perceived particular can be relevantly assimilated. How that background framework is assembled in the first place is the motivating mystery, and the primary target, of Churchland's book. Unexpectedly, this neurobiologically grounded account of human cognition also provides a systematic story of how such low-level epistemological activities are integrated within an enveloping framework of linguistic structures and regulatory mechanisms at the social level. As Churchland illustrates, this integration of cognitive mechanisms at several levels has launched the human race on an epistemological adventure denied to all other terrestrial creatures. (shrink)

This book explores the intersection of legal frameworks, healthcare innovation, and computational intelligence, shedding light on how emerging technologies like AI and ML are reshaping the medical landscape. It presents real life challenges such as patient privacy, data security, and compliance issues in smart healthcare by engaging into associated ethical and regulatory implications. Comprising the concepts of predictive analytics, regulatory compliance algorithms, and legal decision-making processes, this book offers a roadmap for stakeholders to navigate the evolving landscape of (...) healthcare innovation responsibly and ethically. Investigates how artificial intelligence supports legal decision-making processes in smart healthcare, addressing ethical and accountability concerns Demonstrates the use of smart contracts and automation tools powered by computational intelligence to streamline legal processes and ensure compliance in smart healthcare initiatives Focuses on managing healthcare data within legal frameworks, emphasizing computational intelligence's role in ensuring privacy and security. Examines how computational intelligence enables predictive analytics models to anticipate legal challenges and compliance issues in smart healthcare. Highlights the development and implementation of computational algorithms for navigating evolving legal frameworks in healthcare. This reference book is a useful resource for scholars and researchers working on smart healthcare. (shrink)

This article provides a comparative analysis of the regulatory landscapes governing artificial intelligence (AI) in healthcare in the European Union (EU) and South Africa (SA). It critically examines the approaches, frameworks and mechanisms each jurisdiction employs to balance innovation with ethical considerations, patient safety, data privacy and accountability. The EU’s proactive stance, embodied by the AI Act, offers a structured and risk-based categorisation for AI applications, emphasising stringent guidelines for risk management, data governance and human oversight. In contrast, (...) SA’s regulatory environment is characterised by its infancy and lack of specificity, with existing legislation such as the National Health Act and the Medicines and Related Substances Act providing a foundational but limited framework for addressing the unique challenges posed by AI in healthcare. The article delves into the dynamic nature of AI technologies, highlighting the need for continuous risk assessment, the importance of transparent and responsible data governance and the critical role of human oversight in ensuring patient safety and autonomy. It discusses the obligation of clear liability frameworks to address potential malfunctions and security breaches in AI applications. Through this comparative lens, the manuscript identifies regulatory gaps and proposes that the South African Law Reform Commission (SALRC) should play a predominant role in developing draft legislation for AI prior to the evolution of challenges related to these technologies. (shrink)

The proposed federal regulation oforganic agriculture in the United States raisesquestions both about the nature and character oforganic farming, as well as its relation to theagro-food system at large. The regulatory process hasengendered a public debate about conventional andalternative approaches to agricultural production,which in turn raises issues of environmental politicsand society-nature relations. An analysis oftranscripts from public hearings, organic farmingmovement literature, and interviews with organicpractitioners and advocates reveals the broaderecological, social, and political ramifications. Inexamining the proposed federal rule and (...) its criticalopposition, we encounter two different worldviews; twoconflicting visions of agriculture, rural life, andnature itself. Whether this is a fundamental impasse,or a controversy that can be fruitfully resolved,remains an open question. But organic farming hasarrived at a critical juncture, both fraught withperil, and full of opportunity. The enormous publicresponse to this issue indicates the renewed potentialon the part of civil society to participate ingrassroots environmental social movements in supportof alternative agriculture. (shrink)

Assisted reproductive technology is a complex medical intervention with many potential social sensitivities. Within this domain, oocyte cryopreservation has emerged as an important research area for preserving female fertility. Against the backdrop of the hotly debated first legal case in China of a single woman wishing to freeze her eggs, and the implementation of the ‘three‐child policy’ in China, there is an urgent need to evaluate policies and address ethical considerations surrounding oocyte cryopreservation for non‐medical reasons. This review examines current (...) policies, explores China's practices and research, and examines the latest ethical challenges surrounding non‐medical oocyte cryopreservation. It develops strategies and recommendations that will be relevant in China and other developing countries seeking to navigate this complex landscape. (shrink)

The Passenger Name Record (PNR) Directive has introduced a pre-emptive, risk-based approach in the landscape of European databases and information exchange for security purposes. The article contributes to ongoing debates on algorithmic security and data-driven decision-making by fleshing out the specific way in which the EU PNR-based approach to security substantiates core characteristics of algorithmic regulation. The EU PNR framework appropriates data produced in the commercial sector for generating security-related behavioural predictions and does so in a way that gives rise (...) to a paradoxical normativity directly dependent on empirical states. Its ‘securitisation move’ is moreover characterised by an inherent tendence to expand. As a result, the PNR Directive poses challenges for existing check and balance mechanisms and for human autonomy. These challenges could be partially addressed by strengthening ex-post control procedures and independent auditing. Yet in the decision to adopt a risk-based security model, something more fundamental seems to be at stake, namely, the preservation of the idea of human beings as moral agents able to direct and modify their behaviour in accordance with an intelligible, reliable and predictable normative order. (shrink)

The key role played by online platforms in the neo-intermediation of the public debate requires a review of current tools for mapping the digital information ecosystem, highlighting the political nature of such an analysis: Starting from a synoptic overview of the main models of platform governance, we try to understand whether the ongoing European shift towards the Limited Government Regulation (LGR) model will be able to counterbalance the “systemic opinion power” of the giant platforms and restore the “health” of the (...) digital information ecosystem. A close analysis of the European Digital Services Act (DSA) has highlighted some limitations in achieving its goals, because of the features of the LGR on the one hand, and the disruptive features of the algorithmic neo-intermediation phenomenon on the other. Thus, we suggest a tripartite regulatory model, that can be defined as “neo-editorial accountability.” However, increasing users’ critical algorithmic awareness is an essential prerequisite for implementing the suggested template, and mitigating an outstanding effect of the LGR model: the normalization of the ideological assumptions underlying informational capitalism. (shrink)

Scientific knowledge and technological expertise continue to evolve rapidly. Such innovation gives rise to new benefits as well as risks, at an ever-increasing pace. Within this context, regulatory regimes must function in order to address policymakers’ objectives. Innovation, though, can challenge the functioning and effectiveness of regulatory regimes. Questions over fit, effectiveness, and capacity of these regimes to ensure the safe entry of such technologies, and their products, onto the market will be asked in parallel to their development. (...) With this in mind, this article examines the strengths and weaknesses of current regulatory frameworks, including those designed for biotechnology, cosmetics, novel organisms, and foods, in order to inform and help shape Australia’s regulatory landscape around innovation. By focusing on Australia, the article illustrates the need to assess future changes to regulatory frameworks using a careful balancing of key factors. These include, for example, horizon scanning and monitoring, availability of appropriate data, existing health, safety, environmental, ethical, and social risks and impacts, and regulatory capacity. The article argues that rather than using one of these factors in isolation, a careful assessment of where each factor stands can lead regulators to an approach that properly manages the potential risks of emerging technologies. (shrink)

The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research (...) based on sharing, causing confusion about what is allowed, where and when. In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers. (shrink)

In this paper, we distinguish between different sorts of assessments of algorithmic systems, describe our process of assessing such systems for ethical risk, and share some key challenges and lessons for future algorithm assessments and audits. Given the distinctive nature and function of a third-party audit, and the uncertain and shifting regulatory landscape, we suggest that second-party assessments are currently the primary mechanisms for analyzing the social impacts of systems that incorporate artificial intelligence. We then discuss two kinds of (...) as-sessments: an ethical risk assessment and a narrower, technical algo-rithmic bias assessment. We explain how the two assessments depend on each other, highlight the importance of situating the algorithm within its particular socio-technical context, and discuss a number of lessons and challenges for algorithm assessments and, potentially, for algorithm audits. The discussion builds on our team’s experience of advising and conducting ethical risk assessments for clients across dif-ferent industries in the last four years. Our main goal is to reflect on the key factors that are potentially ethically relevant in the use of algo-rithms, and draw lessons for the nascent algorithm assessment and audit industry, in the hope of helping all parties minimize the risk of harm from their use. (shrink)

Recent advancements in AI have prompted a large number of AI ethics guidelines published by governments and nonprofits. While many of these papers propose concrete or seemingly applicable ideas, few philosophically sound proposals are made. In particular, we observe that the line of questioning has often not been examined critically and underlying conceptual problems not always dealt with at the root. In this paper, we investigate the nature of ethical AI systems and what their moral status might be by first (...) turning to the notions of moral agency and patience. We find that their explication would come at a too high cost which is why we, second, articulate a different approach that avoids vague and ambiguous concepts or the problem of other minds. Third, we explore the impact of our philosophical and conceptual analysis on the regulatory landscape, make this link explicit, and finally propose a set of promising policy steps. (shrink)

A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues (...) related to the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one. (shrink)

Biobank research and genomic information are changing the way we look at health and medicine. Genomics challenges our values and has always been controversial and difficult to regulate. In the future lies the promise of tailored medical treatments and pharmacogenomics but the borders between medical research and clinical practice are becoming blurred. We see sequencing platforms for research that can have diagnostic value for patients. Clinical applications and research have been kept separate, but the blurring lines challenges existing regulations and (...) ethical frameworks.Then how do we regulate it? This book contains an overview of the existing regulatory landscape for biobank research in the Western world and some critical chapters to show how regulations and ethical frameworks are developed and work. How should international sharing work? How design an ethical informed consent? An underlying critique: the regulatory systems are becoming increasingly complex and opaque. The international community is building systems that should respond to that. According to the authors in fact, it is time to turn the ship around. Biobank researchers have a moral responsibility to look at and assess their work in relation to the bigger picture: the shared norms and values of current society. Research ethics shouldn't only be a matter of bioethicists writing guidelines that professionals have to follow. Ethics should be practiced through discourse and regulatory frameworks need to be part of that public discourse. Ethics review should be then not merely application of bureaucracy and a burden for researchers but an arena where researchers discuss their projects, receive advice and practice their ethics skills. (shrink)

Lack of guidance and regulation for authorizing medical cannabis for conditions involving the health and neurodevelopment of children is ethically problematic as it promulgates access inequities, risk-benefit inconsistencies, and inadequate consent mechanisms. In two virtual sessions using participatory action research and consensus-building methods, we obtained perspectives of stakeholders on ethics and medical cannabis for children and youth. The sessions focused on the scientific and regulatory landscape of medical cannabis, surrogate decision-making and assent, and the social and political culture of (...) medical cannabis. We found that evidence-gathering and data dissemination, pressures on clinical relationships, and the lack of integration of culturally diverse perspectives and Indigenous knowledges were key areas of concern. Participants emphasized the importance of utilizing adaptive study designs, highlighted the importance of trust-building between clinicians, patients and caregivers, and discussed barriers including historical and ongoing stigmatization of medical cannabis. We conclude that continued public consultation and strength-based research that integrate diverse perspectives are critical steps forward. (shrink)

The nomination of candidate genes underlying complex traits is often focused on genetic variations that alter mRNA abundance or result in non‐conservative changes in amino acids. Although inconspicuous in complex trait analysis, genetic variants that affect splicing or RNA editing can also generate proteomic diversity and impact genetic traits. Indeed, it is known that splicing and RNA editing modulate several traits in humans and model organisms. Using high‐throughput RNA sequencing (RNA‐seq) analysis, it is now possible to integrate the genetics of (...) transcript abundance, alternative splicing (AS) and editing with the analysis of complex traits. We recently demonstrated that both AS and mRNA editing are modulated by genetic and environmental factors, and potentially engender phenotypic diversity in a genetically segregating mouse population. Therefore, the analysis of splicing and RNA editing can expand not only the regulatory landscape of transcriptome and proteome complexity, but also the repertoire of candidate genes for complex traits. (shrink)

This article compares the landscape of tobacco regulations to the landscape of gun regulations, with a focus on regulations that target youth. This article argues that guns are significantly less regulated compared to tobacco, despite the frequency with which each product causes significant harm to both self and other. Many of the specific ways tobacco is regulated can be applied analogously to firearms while plausibly surviving potential Second Amendment challenges. This article compares the regulatory landscape of tobacco and firearms (...) across six categories: minimum age for purchase, sale by unlicensed individuals, taxation, advertising, graphic warning labels, and zoning. At one time, tobacco was as central — or more so — to American culture as guns are today. However, many decades of public health advocacy led to historic tobacco regulations. Tobacco's regulatory history provides a valuable blueprint for gun regulation, despite Constitutional differences. (shrink)

The development of technologies for the biopreservation of infectious organisms requires careful analysis of benefits and risks. This article reviews the regulatory landscape and oversight responsibilities in the United States in respect to pathogen biopreservation. Focused on two globally significant pathogens, Cryptosporidium and Plasmodium, the article explores advantages and potential risks of biopreservation concerning biosafety, biosecurity and biocontainment.

BackgroundPrivate umbilical cord blood banking is a for-profit industry in which parents pay to store blood for potential future use. Governments have noted the tendency for private banks to oversell the potential for cord blood use, especially in relation to speculative cell therapies not yet supported by clinical evidence. We assessed the regulatory landscape governing private cord bank marketing in Canada.Main bodyBecause the problematic marketing of private cord blood banking for future use often relates to speculative future cell therapies (...) that do not exist and are not being advertised for current clinical use, most private blood bank marketing seems to fall outside Health Canada’s regulatory scope. However, this problematic marketing is regulated by the Competition Bureau pursuant to the Competition Act. While representations relating to future hypothetical treatments may not always be subject to the legal requirement for claim substantiation, the law also prohibits individuals and companies from knowingly or recklessly making representations that are “false or misleading in a material respect.” A representation is materially false or misleading when it could “influence a consumer’s behavior or purchasing decisions,” and consumers are likely to be considered to be “credulous and inexperienced” for the purposes of assessing an advertisement’s general impression. Because all of the potential benefit of the banking is derived from the potential future use of the biological material for health interventions directed toward the customers and their relatives, and because we know the best available medical evidence indicates a very low probability of utility in this context, we can say with confidence that some private cord blood banking claims are materially misleading. Moreover, to the extent that medical professionals are involved in private bank interactions with customers or hold ownership stakes in private banks, they are subject to professional codes, standards of practice, and potentially fiduciary obligations that further prohibit misleading marketing.ConclusionsPrivate cord blood bank marketing that advertises hypothetical future treatments can be misleading and may influence consumer behaviour. This marketing may breach existing advertising law. Regulatory bodies should enforce the law in order to help prevent public health and personal financial harm. (shrink)

While open science gains prominence in South Africa with the encouragement of open data sharing for research purposes, there are stricter laws and regulations around privacy – and specifically the use, management and transfer of personal information – to consider. The Protection of Personal Information Act No. 4 of 2013 (POPIA), which came into effect in 2021, established stringent requirements for the processing of personal information and has changed the regulatory landscape for the transfer of personal information across South (...) African borders. At the same time, draft national policies on open science encourage wide accessibility to data and open data sharing in line with international best practice. As a result, the operation of research ethics committees (RECs) in South Africa is affected by the conflicting demands of the shift towards open science on the one hand, and the stricter laws protecting participants’ personal information and the transfer thereof, on the other. This article explores the continuing evolving role of RECs in the era of open data and recommends the development of a data transfer agreement (DTA) for the ethical management of personal health information, considering the challenges that RECs encounter, which centres predominantly on privacy, data sharing and access concerns following advances in genetic and genomic research and biobanking. (shrink)

Medicine regulation demands the application of sound medical, scientific, and technical knowledge and skills, and operates within a legal framework. Regulatory functions involve interactions with various stakeholders (e.g., manufacturers, traders, consumers, health professionals, researchers, and governments) whose economic, social, and political motives may differ, making implementation of regulation both politically and technically challenging. This book discusses regulatory landscape globally and the current global regulatory scenario of medicinal products and food products comprehensively.

We apply Ken Wilber's Integral Theory to AI governance, demonstrating its ability to systematize diverse approaches in the current multifaceted AI governance landscape. By analyzing ethical considerations, technological standards, cultural narratives, and regulatory frameworks through Integral Theory's four quadrants, we offer a comprehensive perspective on governance needs. This approach aligns AI governance with human values, psychological well-being, cultural norms, and robust regulatory standards. Integral Theory’s emphasis on interconnected individual and collective experiences addresses the deeper aspects of AI-related issues. (...) Additionally, we propose using Integral Theory as a methodology for literature reviews to overcome the fragmented understanding often seen in traditional reviews of AI governance. (shrink)

The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor states that (...) emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust. (shrink)

In the ever-evolving landscape of Artificial Intelligence in Healthcare (AIH), understanding the entities and legal frameworks governing its research and development is crucial. This report delves into the intricacies of AIH in Malaysia, undertaking a comprehensive literature search on scientific databases, government portals, and news sources. Additionally, bibliometric analysis has been concurrently conducted to discern trends and developments in AIH over the years. Notably, the interest in AIH has seen a consistent rise since 2017, marked by a growing number of (...) use cases (25 reported here) developed by both local and foreign innovators and applicators. Despite this surge in research and adoption, Malaysia lacks direct legislation specifically addressing AIH technologies, leaving them subject to 11 existing laws. This lack of clear oversight is compounded by the insufficient expertise within local regulatory and ethical bodies to effectively assess AIH research and deployment. The resultant challenges include bureaucratic hurdles for AIH innovators and applicators, raising ethical concerns related to patient autonomy, privacy, data management, AI robustness, and liability. To address these issues, this paper recommends: (1) adopting international ethical guidelines for AIH, (2) enhancing public awareness and education on AI technologies, and (3) promoting AIH research through clinical or silent trials to improve oversight and foster innovation. (shrink)

In the nearly 40 years since implementation of federal regulations governing the protection of human participants in research, the number of clinical studies has grown exponentially. These studies have become more complex, with multisite trials now common, and there is increasing use of archived biospecimens and related data, including genomics data. In addition, growing emphasis on targeted cancer therapies requires greater collaboration and sharing of research data to ensure that rare patient subsets are adequately represented. Electronic records enable more extensive (...) data collection and mining, but also raise concerns about the potential for inappropriate or unauthorized use of data, bringing patient protections into a new landscape. There are also long-standing concerns about the processes and forms used to obtain informed consent from patients participating in clinical studies. These changes and challenges raise new ethical and practical questions for the oversight of clinical studies, and for protecting patients and their health information in an efficient manner that does not compromise the progress of biomedical research. Contemporary Issues for Protecting Patients in Cancer Research is the summary of a workshop convened by the National Cancer Policy Forum of the Institute of Medicine in February 2014 to explore contemporary issues in human subjects protections as they pertain to cancer research, with the goal of identifying potential relevant policy actions. Clinical researchers, government officials, members of Institutional Review Boards, and patient advocates met to discuss clinical cancer research and oversight. This report examines current regulatory provisions that may not adequately protect patients or may be hindering research, and discusses potential strategies and actions to address those challenges. (shrink)

The complex regulatory framework governing the U.S. health care system can be an obstacle to programming that address health-related social needs. In particular, health care fraud and abuse law is a pernicious barrier as health care organizations may minimize or forego programming altogether out of real and perceived concern for compliance. And because health care organizations have varying resources to navigate and resolve compliance concerns, as well as different levels of risk tolerance, fears related to the legal landscape may (...) further entrench inequities in access to meaningful programs that improve health outcomes. This article uses food and nutrition programming as a case study to explore the complexities presented by this area of law and to highlight pathways forward. (shrink)

_The traditional landscape of employment, once structured around full-time positions with defined benefits, is experiencing a seismic shift. The gig economy, a burgeoning ecosystem of flexible, on-demand work arrangements, has emerged as a powerful force, reshaping labor markets and blurring the lines between employee and independent contractor. This article delves into the intricate labyrinth of the gig economy, analyzing its multifaceted impacts on workers, businesses, and policymakers. By navigating this labyrinth of potential benefits, challenges, and ethical considerations, we can illuminate (...) the pathways towards harnessing the gig economy's potential while mitigating its risks and ensuring fair and equitable outcomes for all participants._. (shrink)

Multi-stakeholder initiatives have become a vital part of the organizational landscape for corporate social responsibility. Recent debates have explored whether these initiatives represent opportunities for the “democratization” of transnational corporations, facilitating civic participation in the extension of corporate responsibility, or whether they constitute new arenas for the expansion of corporate influence and the private capture of regulatory power. In this article, we explore the political dynamics of these new governance initiatives by presenting an in-depth case study of an organization (...) often heralded as a model MSI: the Forest Stewardship Council. An effort to address global deforestation in the wake of failed efforts to agree a multilateral convention on forests at the Rio Summit in 1992, the FSC was launched in 1993 as a non-state regulatory experiment: a transnational MSI, administering a global eco-labeling scheme for timber and forest products. We trace the scheme’s evolution over the past two decades, showing that while the FSC has successfully facilitated multi-sectoral determination of new standards for forestry, it has nevertheless failed to transform commercial forestry practices or stem the tide of tropical deforestation. Applying a neo-Gramscian analysis to the organizational evolution of the FSC, we examine how broader market forces and resource imbalances between non-governmental and market actors can serve to limit the effectiveness of MSIs in the current neo-liberal environment. This presents dilemmas for NGOs which can lead to their defection, ultimately undermining the organizational legitimacy of MSIs. (shrink)

A multitude of legislation impacts the use of samples and data for research in South Africa. With the coming into effect of the Protection of Personal Information Act No. 4 of 2013 in July 2021, recent attention has been given to safeguarding research participants’ personal information. The protection of participants’ privacy in research is essential, but it is not the only risk at stake in the use and sharing of personal information. Other rights and interests that must also be considered (...) and safeguarded include the right to non-discrimination, the right to dignity, and the right to enjoy the benefits of scientific progress. This can be achieved by ensuring that the ethical values and universal principles that underpin the research landscape, namely equity, reciprocity, justice and solidarity, are embedded in the regulatory framework for the management and use of personal information. This paper advocates an integrated bioethics approach to the use of personal information for research in SA. A key feature in embedding such an approach is a Data Transfer Agreement that appropriately integrates the safeguards and protections set out by our regulatory framework with bioethical rules and procedures when personal information is used and shared for research purposes. This paper thus calls for the development of a national DTA that is guided by key ethical principles when data are shared for research purposes. This paper will be followed by a webinar on 23 June 2022 hosted by the Department of Science and Innovation and the SA Medical Research Council, where the recommendations and suggestions set out herein will be unpacked, discussed and debated by relevant stakeholders. (shrink)

Background The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs). Methods We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during (...) public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach. Results Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically. Conclusions There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics. (shrink)

By many accounts, CRISPR gene-editing technology is revolutionizing biotechnology. It has been hailed as a scientific game changer and is being adopted at a break-neck pace. This hasty adoption has left little time for ethical reflection, and so this paper aims to begin filling that gap by exploring whether CRISPR is as much an ethical game changer as it is a biological one. By focusing on the application of CRISPR to non-human animals, I argue that CRISPR has and will continue (...) to result in significant shifts in the ethical debate landscape. For instance, the fact that many CRISPR edits are non-transgenic has important implications for the ethical debate, particularly the popular objection to genetic engineering that it objectionably involves “crossing species boundaries,” as well as the regulatory debate in the United States, where currently only transgenic organisms are officially genetically modified organisms. I also explore various impacts CRISPR may have on animal welfare, suggesting that although the improved precision of CRISPR suggests fewer unintended welfare problems in comparison to past techniques, the greater versatility means that more animals than ever will be engineered. Finally, I end my discussion of animal welfare issues by exploring the possibility of using CRISPR to directly improve animal welfare, for instance through introducing disease resistance. (shrink)

ABSTRACT:The literatures of business ethics and international business have generally had little influence on each other. Nevertheless, the decline in the power of nation states, the emergence of non-governmental organizations, the proliferation of self-regulatory bodies, and the changing responsibilities, roles, and structure of multinational corporations make constructive engagement between these two disciplines imperative. This changing institutional landscape creates many areas of common concern. In this article, we describe the changing institutional context of global business and suggest ways in which (...) both business ethics and international business may inform each other more fruitfully. (shrink)

The payments industry – the business of transferring value through public and corporate infrastructures – is undergoing rapid transformation. New business models and regulatory environments disrupt more traditional fee-based strategies, and new entrants seek to displace legacy players by leveraging new mobile platforms and new sources of data. In this increasingly diversified industry landscape, start-ups and established players are attempting to embed payment in ‘social’ experience through novel technologies of accounting for trust. This imagination of the social, however, is (...) being materialized in gated platforms for payment, accounting, and exchange. This paper explores the ambiguous politics of such experiments, specifically those, like Bitcoin or the on-demand sharing economy, that delineate an economic imaginary of ‘just us’ – a closed and closely guarded community of peers operating under the illusion that there are no mediating institutions undergirding that community. This provokes questions about the intersection of payment and publics. Payment innovators’ attenuated understanding of the social may, we suggest, evacuate the nitty-gritty of politics. (shrink)

Novel forms of assisted gestation—uterus transplantation and artificial placentas—are highly anticipated in the ethico‐legal literature for their capacity to enhance reproductive autonomy. There are also, however, significant challenges anticipated in the development of novel forms of assisted gestation. While there is a normative exploration of these challenges in the literature, there has not yet, to my knowledge, been empirical research undertaken to explore what reproductive rights organisations and advocates identify as potential benefits and challenges. This perspective is invaluable. These organisations/individuals (...) have an awareness not only of the needs of individuals but also of the political landscape in which regulatory decisions are made and which individuals navigate when seeking reproductive assistance. In this study, data was generated from two semi‐structured focus groups (n = 11). Reflective thematic analysis was used to examine the views raised by study participants in these focus groups. This paper explores two of the themes constructed in the data. First, the equality‐enhancing potential of assisted gestation exploring the multifaceted ways in which assisted gestation has structural benefits for marginalised groups. Second, realising the equality‐enhancing potential of assisted gestation explores the intersecting barriers to access to reproductive technologies and how they may impede the benefits of these technologies in practice. These results can enhance conceptual understanding of the importance of novel forms of assisted gestation and ensure that attention is paid to practical barriers in further normative research. (shrink)

AbstractIn many cultures, interactions between humans and plants are rooted in what is called “relational values”—values that derive from relationships and entail reciprocity. In Mexico, biocultural diversity is mirrored in the knowledge and use of some 6500 plant species and the domestication of over 250 Mesoamerican native crop species. This research explores how different sets of values are attributed to plants and how these influence management strategies to maintain plant resources in wild and anthropogenic environments. We ran workshops in two (...) communities in a highly biodiverse region in western Mexico, to ascertain the values and management activities related to important plant resources. The relationship between values attributed to plants and management activities was examined through redundancy analysis. A total of 180 plant resources were mentioned during the workshops, with a broad spectrum of values attributed to them, including material, non-material, and regulatory dimensions. We divided plant management strategies into three general categories of increasing intensity and complexity. We found that participants in the Indigenous community value and manage more wild plant resources than people in the non-Indigenous community. We also identified relationships between plant resource values and the type of management performed; for example, more intensive forms of management, such as sowing seeds, were used for seasonal plants that had a food value. By valuing and managing different sets of plant resources from forest, agricultural plots, and home gardens, people enabled multi-functional landscapes to form, illustrating a key feature of relational values in agroecosystems, which promotes both conservation and domestication of plants. (shrink)

The chapter shows how the recognition of reflexivity of emotions is crucial for understanding the role of emotions in reasoning because it highlights the regulatory role of emotion in emotional experience. The chapter begins by showing that to attain a conception of rationality that incorporates feelings, emotions, and sentiments as parts of the reasoning processes requires capturing the emotional landscape in all its complexity, and that integrating the role of meta-emotions is a contribution in that direction. Then introducing the (...) notion of meta-emotions and showing how emotional reflexivity modifies the nature of our emotional world, it is shown how emotions also have a regulatory mechanism that can either be maladaptive or at the center of emotional health. In addition, because meta-emotions provide a test for the more general assumptions of theories of emotions, the chapter ends by showing how adopting a Situated Approach to Emotions is well-suited for explaining the refinement and complexity of emotion regulation. The final reflection of the chapter explains why adopting such theoretical frame of work makes it possible to use the term situation in a technical manner, which then reveals that emotions sometimes are described as causes while other times as reasons in connection to their regulative mechanisms. (shrink)

This book examines the ethics of virtual reality technologies. New forms of virtual reality are emerging in society, not just from low-cost gaming headsets, or augmented reality apps on phones, but from simulated “deep fake” images and videos on social media. This book subjects the new VR technological landscape to ethical scrutiny: assessing the benefits, risks and regulatory practices that shape it. Though often associated with gaming, education and therapy, VR can also be used for moral enhancement. Journalists, artists, (...) philanthropic and non-governmental organisations are using VR films, games and installations to stimulate user empathy to marginalised peoples through a combination of immersion, embodiment and persuasion. This book critically assesses the use of VR for empathy arousal and pro-social behaviour change, culminating in the development of a VR “ethical tool” – a device to facilitate reflective ethical judgement. Drawing upon the pragmatist philosophy of John Dewey, virtual reality is reshaped as “dramatic rehearsal”. This book explains how a combination of immersive environment-building, moral imagination, choice architecture and reflective engagement can stimulate a future-focused and empathic ethics for users of the technology. (shrink)