Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability. An (...) improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine. Epigenetic and transcriptional variability mediate phenotypic plasticity, enabling adaptation to changing environments. In this review, we describe the sources of inter- and intra-individual variability and discuss epigenetic regulators of gene expression variability, including DNA methylation and chromatin structure. Understanding these molecular mechanisms will improve therapeutic approaches and personalized medicine. (shrink)

The permanent struggle for optimisation can be seen as one of the most significant cultural principles of contemporary Western societies: the demand for improved performance and efficiency as well as the pursuit of self-improvement are con-sidered necessary in order to keep pace with an accelerated, competitive modern-ity. This affects not only work and education, but also family life, parent–child relationships and intimate relationships in respect to the body and the self, in regard to the public as well as the private (...) realm. Bringing together contributions from renowned scholars from the fields of sociology, psychology and psycho-analysis, this book explores the impacts of optimisation on culture and psyche, examining the contradictions and limitations of optimisation, in conjunction with the effects of social transformations on individuals and shifts in regard to the meaning of ‘pathology’ and ‘normality’. (shrink)

In a time marked by the development of innovative treatments in healthcare and the need for health professionals to deal with resulting ethical dilemmas in clinical practice, this study was developed to determine the influence of the bioethics teaching on the moral competence of medical and nursing students. The authors conduct a longitudinal study using the Moral Competence Test extended version before and after attending the ethics curricular unit, in three nursing schools and three medical schools of Portugal. In this (...) questionnaire the participant is confronted with three ethical dilemmas and asked to evaluate arguments for and against the attitude of the main character. For both nursing and medical students, C-score was lower after the attendance of the ethics curricular units, with a statistically significant decrease in the total score for nursing students and a decrease not statistically significant for medical students. A multivariate analysis did not find any association between this decrease and gender, course, or age. The phenomenon of moral segmentation was observed, with better performance in the worker and judge dilemma, than in the doctor dilemma. These results highlight the need to reflect on the curricular strategies that can be implemented for health professionals to better develop moral competence and decision-making, allowing for the provision of humanized health care. (shrink)

We show that in the Maxwell–Lorentz theory of classical electrodynamics most initial values for fields and particles lead to an ill-defined dynamics, as they exhibit singularities or discontinuities along light-cones. This phenomenon suggests that the Maxwell equations and the Lorentz force law ought rather to be read as a system of delay differential equations, that is, differential equations that relate a function and its derivatives at different times. This mathematical reformulation, however, leads to physical and philosophical consequences for the ontological (...) status of the electromagnetic field. In particular, fields cannot be taken as independent degrees of freedom, which suggests that one should not add them to the ontology. (shrink)

Many arguments have been made against gene editing. This paper addresses the commonly invoked argument that gene editing violates human dignity and is ultimately a subversion of human nature. There are several drawbacks to this argument. Above all, the concept of what human dignity means is unclear. It is not possible to condemn a practice that violates human dignity if we do not know exactly what is being violated. The argument’s entire reasoning is thus undermined. Analyses of the arguments involved (...) in this discussion have often led to the conclusion that gene editing contravenes the principle of genetic identity (genetic immutability) thereby subverting a requisite of human dignity and ultimately threatening human nature. This paper refutes these arguments and shows that any opposition to gene editing cannot rely on the human dignity argument. (shrink)

Direitos humanos e o tráfico de drogas : a repercussão do caso "Matemático" nas redes sociais de um debate concreto -- Drogas e governamentalidade : uma análise crítica da recente política criminal legislativa uruguaia -- Entre gritos e jeitinhos : a velha sedução das práticas autoritárias e alguns desafios para uma justiça de transição no Brasil -- "Abolicionismo Real" e liberdade : reflexões em tempos de necessidade de (auto)crítica acadêmica -- Contribuições do abolicionismo de Mathiesen para a realidade punitiva/encarceradora brasileira.

Gift of utterance: expanding vocabularies for truth -- Dainty as candle-lights: veiled truths and shadowy lies -- Philomela and the risk of history -- Truth: a muddy sprout -- No auditors in the courtroom of history.

Charkiw in der Ukraine war in den 1920er-Jahren ein aktives Zentrum der Avantgarde, das mehrfach an Peripherien gelegen war: Räumlich abseits der Machtzentren und zeitlich in der letzten Phase der Avantgarde positioniert, differierten auch die künstlerischen Praktiken des Panfuturismus und des Konstruktiven Dynamismus von tonangebenden Erscheinungen. So wurden etwa in der späten Phase der Avantgarde überholte Konzepte der Abstraktion mit funktionalistischen Ansätzen vereint. Die Formationen Nova Generacija (1927-1931) und Avanhard (1925-1929) mit Mychajl' Semenko und Valerijan Poliscuk an der Spitze interagierten (...) dabei rege mit den Avantgarden in Ost und West.0Vera Faber analysiert nun erstmals umfassend die dabei zum Einsatz kommenden polemischen Praktiken der Aus-, Ab- und Eingrenzung - anhand von Programmtexten und literarischen sowie künstlerischen Arbeiten -- Cover page [4]. (shrink)

One dimension of cognitive success concerns getting it right: having many true beliefs and no false ones. Another dimension of cognitive success concerns using the right concepts. For example, using a concept of a person that systematically excludes people of certain demographics from its extension is a sort of cognitive deficiency. This view, if correct, tasks inquirers with critically examining the concepts they are using and perhaps replacing those concepts with new and better ones. This task is often referred to (...) as “conceptual engineering”. However, so far it is unclear what exactly happens in cases of conceptual engineering. How does language change when we engineer a concept? This article offers an answer. I propose a view on which, when speakers assess the truth of propositions, they often rely on assumptions with regard to what is required for their truth. For example, when speakers assess whether unborn fetuses are people, they rely on assumptions with regard to what is required to be a person. Based on this idea, I develop a model of conceptual engineering according to which speakers “engineer concepts” when they change how they assess the truth of propositions. For example, speakers engineer the concept of a person when they change how they assess the truth of the proposition that unborn fetuses are people. (shrink)

According to the doctrine of Super-Humeanism, the world’s mosaic consists only of permanent matter points and changing spatial relations, while all the other entities and features figuring in scientific theories are nomological parameters, whose role is merely to build the best law system. In this paper, I develop an argument against Super-Humeanism by pointing out that it is vulnerable to and does not have the resources to solve the well-known problem of immanent comparisons. Firstly, I show that it cannot endorse (...) a fundamentalist solution à la Lewis, since its two pillars—a minimalist ontology and a best system account of lawhood—would generate, together, a tedious problem of internal coherence. Secondly, I consider anti-fundamentalist strategies, proposed within Humeanism, and find them inapplicable to the Super-Humean doctrine. The concern is that, since it is impossible to choose the best law system within Super-Humeanism, this doctrine may be charged with incoherence. (shrink)

Although Chinese law imposes informed consent for medical treatments, the Chinese understanding of this requirement is very different from the European one, mostly due to the influence of Confucianism. Chinese doctors and relatives are primarily interested in protecting the patient, even from the truth; thus, patients are commonly uninformed of their medical conditions, often at the family’s request. The family plays an important role in health care decisions, even substituting their decisions for the patient’s. Accordingly, instead of personal informed consent, (...) what actually exists is ‘family informed consent’. From a Western perspective, these features of Chinese law and Chinese culture might seem strange, contradicting our understanding of doctor-patient relationship and even the very essence of self-determination and fundamental rights. However, we cannot forget the huge influence of cultural factors in these domains, and that ‘Western’ informed consent is grounded on the individualistic nature of Western culture. This article will underline the differences between the Western and the Chinese perspectives, clarifying how each of them must be understood in its own cultural environment. But, while still respecting Chinese particularities, this paper advocates that China adopt patient individual informed consent because this is the only solution compatible with human dignity and human rights. (shrink)

Do numbers exist? Carnap (1956 [1950]) famously argues that this question can be understood in an “internal” and in an “external” sense, and calls “external” questions “non-cognitive”. Carnap also says that external questions are raised “only by philosophers” (p. 207), which means that, in his view, philosophers raise ”non-cognitive” questions. However, it is not clear how the internal/external distinction and Carnap’s related views about philosophy should be understood. This paper provides a new interpretation. I draw attention to Carnap’s distinction between (...) purely external statements, which are independent from all frameworks, and pragmatic external statements, which concern which framework one should adopt, and argue that the latter express noncognitive mental states. Specifically, I argue that “frameworks” are systems of rules for the assessment of statements, which are utterances of ordinary language sentences. Pragmatic external statements express noncognitive dispositions to follow only certain rules of assessment. For instance, “numbers exist” understood as a pragmatic external statement expresses a noncognitive disposition to use only rules of assessment according to which numbers do exist. Carnap can thereby be understood as proposing a distinctive form of noncognitivism about ontology that is in some respects analogous to norm-expressivism in metaethics. (shrink)

Ontological expressivism is the view that ontological existence claims express non-cognitive mental states. I develop a version of ontological expressivism that is modeled after Gibbard’s (2003) norm-expressivism. I argue that, when speakers assess whether, say, composite objects exist, they rely on assumptions with regard to what is required for composition to occur. These assumptions guide their assessment, similar to how norms may guide the assessment of normative propositions. Against this backdrop, I argue that “some objects have parts”, uttered in the (...) context of an ontological disagreement, expresses a noncognitive disposition to assess the truth of propositions by using only rules of assessment according to which the proposition that some objects have parts is to be evaluated as true. (shrink)

The events surrounding COVID-19, combined with the mandatory quarantines widely imposed in Asia and Europe since the virus outbreak, have reignited discussion of the balance between individual rights and liberties and public health during epidemics and pandemics. This article analyses this issue from the perspectives of precaution and necessity. There is a difficult relationship between these two seemingly opposite principles, both of which are frequently invoked in this domain. Although the precautionary principle encourages the use of quarantines, including mandatory quarantines, (...) and associated restrictive measures, the principle of necessity puts a break on such measures. The COVID-19 pandemic reveals once again the different interrelations between these two principles. However, the alleged conflict between the PN and the PP is based on a superficial analysis. The relation between these two principles is far more complex, as this article will demonstrate. (shrink)

This is the first monograph devoted to the theology of the Epinomis. It argues that the work offers a revised Platonic conception of the divine better suited to the political imperatives of the post-Classical age. The Epinomis is an 'appendix' to Plato's Laws written by Plato's student, Philip of Opus. Through a comprehensive analysis of the Epinomis' lexicon, and comparisons with the Corpus Platonicum, Vera Calchi offers readers an insight into the Epinomis' philosophical and historical context, purpose, and legacy. (...) Calchi argues that Philip effectively reshapes Plato's metaphysical language into a theology premised on the immanence of God in the heavens. The resulting account of God's providential activity in the cosmos, which offers a new way of thinking about morality and political order, can be regarded as a major step towards the cosmic theology of the Hellenistic period. The Theology of the Epinomis is suitable for students and scholars of ancient philosophy, particularly those working on the Epinomis and Platonic philosophy. It will also be of interest to those studying the history of religion and theology in antiquity. (shrink)

The possibility of neurotechnological interference with our brain and mind raises questions about the moral rights that would protect against the (mis)use of these technologies. One such moral right that has received recent attention is the right to mental integrity. Though the metaphysical boundaries of the mind are a matter of live debate, most defences of this moral right seem to assume an internalist (brain-based) view of the mind. In this article, we will examine what an extended account of the (...) mind might imply for the right to mental integrity and the protection it provides against neurotechnologies. We argue that, on an extended account of the mind, the scope of the right to mental integrity would expand significantly, implying that neurotechnologies would no longer pose a uniquely serious threat to the right. In addition, some neurotechnologies may even be protected by the right to mental integrity, as the technologies would becomepart ofthe mind. We conclude that adopting an extended account of the mind has significant implications for the right to mental integrity in terms of its protective scope and capacity to protect against neurotechnologies, demonstrating that metaphysical assumptions about the mind play an important role in determining the moral protection provided by the right. (shrink)

This paper examines the culture, the dynamics and the financial underpinnings that determine how medical research is being conducted on children in the United States. Children have increasingly become the subject of experiments that offer them no potential direct benefit but expose them to risks of harm and pain. A wide range of such experiments will be examined, including a lethal heartburn drug test, the experimental insertion of a pacemaker, an invasive insulin infusion experiment, and a fenfluramine "violence prediction" experiment. (...) Emphasis, however, is given to psychoactive drug tests because of the inherent ethical and diagnostic problems involved in the absence of any objective, verifiable diagnostic tool. Effort is made to provide readers comprehensive reference sources to evidence-based reports about the serious risks these drugs pose for adults and children so that the reader may judge whether the benefits (if any) outweigh the risks for children. The first ethical issue raised by these experiments is: did the severity of illness in these children justify their exposure to short and long-term risks? The ethics of the experiments will be evaluated by referring to existing codes of medical research ethics-the Nuremberg Code, the Declaration of Helsinki, and the federal Code of Regulations. The thirteen cases presented will demonstrate that children are being used in ever more speculative experiments, often in the absence of a therapeutic intent, but a significant chance for causing harm and / or discomfort. Some of the experiments were designed to explore the mechanisms of pathology and pharmacological interventions, or the response of neurological brain receptors to chemical provocation ("challenge"). Others were designed to test the safety or efficacy of new drugs, even to test these drugs on healthy children who were hypothesized to be "at risk." Children and adolescents have been subjected to "forced dose titration" experiments that induced a spectrum of severe adverse effects, including insomnia, extreme restlessness, agitation, (akathisia) and self-injurious behavior. FDA reports show that suicide is a significant issue in psychotropic drug trials-in pediatric trials the problem is even greater. The paper aims to demonstrate how the enactment of the Better Pharmaceuticals for Children Act (incorporated into the Food and Drug Administration Modernization Act, FDAMA), set in motion a radical shift in public policy by providing huge financial incentives to pharmaceutical companies to test new or patented drugs in children. Federal policy shifted from one aimed at protecting children by setting limits on permissible research risks, to a policy aimed at broadening the inclusion of children as test subjects. It will be shown how the FDA and the Department of Health and Human Services lifted regulatory restrictions to permit research involving greater than minimal risk to be conducted on healthy children, claiming that all children are potentially "at risk" of a future condition. Children were in this way deprived of regulatory protections. An argument will be made that the approval of nontherapeutic, harmful experiments-such as exposure of toddlers to lead poison-under the current gate keeping system raises serious doubts about the sustainability of institutional review boards (IRBs) as protectors of human research subjects. Children, who are precluded from exercising the adult human's right to informed consent, are being exploited as commodities for commercial ends. It is the position of the author that nothing less than the enactment of a federal law mandating a radical overhaul of the current research review system, with independent checks and balances, will provide children the legal protections they need. Ten specific recommendations are offered to protect children from harmful experiments. (shrink)