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)

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 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)

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)

The Director-General of the WHO has suggested that China’s approach to the COVID-19 crisis could be the standard of care for global epidemics. However, as remarkable as the Chinese strategy might be, it cannot be replicated in other countries and certainly not in Europe. In Europe, there is a distribution of power between the European Union and its member states. In contrast, China’s political power is concentrated in the central government. This enables it to take immediate measures that affect the (...) entire country, such as massive quarantines or closing borders. Moreover, the Chinese legal framework includes restrictions on privacy and other human rights that are unknown in Europe. In addition, China has the technological power to easily impose such restrictions. In most European countries, that would be science fiction. These conditions have enabled China to combat epidemics like no other country can. However, the WHO might have been overoptimistic. The Chinese standard of care for treating COVID-19 also raises problematic issues for human rights, and the real consequences of these actions remain to be seen. (shrink)

We show that is consistent with the existence of a -definable wellorder of the reals and a -definable ω-mad subfamily of [ω]ω.

Using countable support iterations of S-proper posets, we show that the existence of a definable wellorder of the reals is consistent with each of the following: , and.

Comprehensive regulatory changes brought on by recent corporate governance reforms have broadly redefined and re-emphasized the roles and responsibilities of all the participants in a public company’s financial reporting process. Most notably, these reforms have intensified scrutiny of corporate audit committees, whose role as protectors of investors’ interests now attracts substantially higher visibility and expectations. As a result, audit committees face the formidable challenge of effectively overseeing the company’s financial reporting process in a dramatically changed – and highly charged – (...) corporate governance environment. This paper discusses the new expectations of audit committee responsibilities and effectiveness in the wake of corporate governance reforms, key challenges, “whistleblower” provisions and shortcomings, and provides some directions for future research. (shrink)

Health care often involves ethically difficult situations that may disquiet the conscience. The purpose of this study was to develop a questionnaire for identifying various perceptions of conscience within a framework based on the literature and on explorative interviews about perceptions of conscience (Perceptions of Conscience Questionnaire). The questionnaire was tested on a sample of 444 registered nurses, enrolled nurses, nurses’ assistants and physicians. The data were analysed using principal component analysis to explore possible dimensions of perceptions of conscience. The (...) results showed six dimensions, found also in theory and empirical health care studies. Conscience was perceived as authority, a warning signal, demanding sensitivity, an asset, a burden and depending on culture. We conclude that the Perceptions of Conscience Questionnaire is valid for assessing some perceptions of conscience relevant to health care providers. (shrink)

We study the set of possible sizes of maximal independent families to which we refer as spectrum of independence and denote \\). Here mif abbreviates maximal independent family. We show that:1.whenever \ are finitely many regular uncountable cardinals, it is consistent that \\); 2.whenever \ has uncountable cofinality, it is consistent that \=\{\aleph _1,\kappa =\mathfrak {c}\}\). Assuming large cardinals, in addition to above, we can provide that $$\begin{aligned} \cap \hbox {Spec}=\emptyset \end{aligned}$$for each i, \.

Incest is a crime in most societies. In the United States, incest is punishable in almost every state with sentences going as far as 20 and 30 years in prison, and even a life sentence. Yet the reasons traditionally proffered in justification of criminalization of incest—respecting religion and universal tradition; avoiding genetic abnormalities; protecting the family unit; preventing sexual abuse and sexual imposition; and precluding immorality—at a close examination, reveal their under- and over-inclusiveness, inconsistency or outright inadequacy. It appears that (...) the true reason behind the long history of the incest laws is the feeling of repulsion and disgust this tabooed practice tends to evoke in the majority of population. However, in the absence of wrongdoing, neither a historic taboo nor the sense of repulsion and disgust legitimizes criminalization of an act. (shrink)

ABSTRACTPrevious research suggests that labelling emotions, or describing affective states using emotion words, facilitates emotion regulation. But how much labelling promotes emotion regulation? And which emotion regulation strategies does emotion labelling promote? Drawing on cognitive theories of emotion, we predicted that labelling emotions using fewer words would be less confusing and would facilitate forms of emotion regulation requiring more cognitively demanding processing of context. Participants mentally immersed themselves in an emotional vignette, were randomly assigned to an exhaustive or minimal emotion (...) labelling manipulation, and then completed an emotion regulation strategy planning task. Minimal emotion labelling promoted higher subjective emotional clarity. Furthermore, in terms of specific emotion regulation strategies, minimal emotion labelling prompted more plans for problem solving and marginally more plans for reappraisal, but did not affect plans for behav... (shrink)

The aim of this paper is to define a notion of supervenience which can adequately describe the systematic dependence of extrinsic as well as of intrinsic higher-level properties on base-level features. We argue that none of the standard notions of supervenience—the concepts of weak, strong and global supervenience—fulfil this function. The concept of regional supervenience, which is purported to improve on the standard conceptions, turns out to be problematic as well. As a new approach, we develop the notion of property-dependent (...) supervenience. This notion is founded on a criterion of relevance adapting the supervenience base to the considered higher-level properties in a specific way, such that only features which are relevant to the instantiation of the higher-level properties under consideration are taken into account. (shrink)

Popper’s ‘Situational Analysis’ constitutes his methodological proposal for the social sciences. We claim that the two hallmarks of SA are: that scientists assume they possess a ‘wider’ view of the problem-situation than actors do, and use the model as an ideal ‘benchmark’ scenario to identify the deviation of actors’ actual behaviour from the former. We argue that SA is not a generalization of the neoclassical theory of individual behaviour but captures instead the methodology adopted by modern behavioural economists. Last, we (...) argue that SA highlights a way of acquiring knowledge that has gone unnoticed in the literature. (shrink)

We extend the work of Fischer et al. [6] by presenting a method for controlling cardinal characteristics in the presence of a projective wellorder and 2ℵ0>ℵ2. This also answers a question of Harrington [9] by showing that the existence of a Δ31 wellorder of the reals is consistent with Martinʼs axiom and 2ℵ0=ℵ3.

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)

The monitoring role performed by the board of directors is an important corporate governance control mechanism, especially in countries where external mechanisms are less well developed. The gender composition of the board can affect the quality of this monitoring role and thus the financial performance of the firm. This is part of the “business case” for female participation on boards, though arguments may also be framed in terms of ethical considerations. While the issue of board gender diversity has attracted growing (...) research interest in recent years, most empirical results are based on U.S. data. This article adds to a growing number of non-U.S. studies by investigating the link between the gender diversity of the board and firm financial performance in Spain, a country which historically has had minimal female participation in the workforce, but which has now introduced legislation to improve equality of opportunities. We investigate the topic using panel data analysis and find that gender diversity – as measured by the percentage of women on the board and by the Blau and Shannon indices – has a positive effect on firm value and that the opposite causal relationship is not significant. Our study suggests that investors in Spain do not penalise firms which increase their female board membership and that greater gender diversity may generate economic gains. (shrink)

We study regularity properties related to Cohen, random, Laver, Miller and Sacks forcing, for sets of real numbers on the Δ31\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varvec{\Delta}^1_3}$$\end{document} level of the projective hieararchy. For Δ21\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varvec{\Delta}^1_2}$$\end{document} and Σ21\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varvec{\Sigma}^1_2}$$\end{document} sets, the relationships between these properties follows the pattern of the well-known Cichoń diagram for cardinal characteristics of the continuum. It is known that (...) assuming suitable large cardinals, the same relationships lift to higher projective levels, but the questions become more challenging without such assumptions. Consequently, all our results are proved on the basis of ZFC alone or ZFC with an inaccessible cardinal. We also prove partial results concerning Σ31\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varvec{\Sigma}^1_3}$$\end{document} and Δ41\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varvec{\Delta}^1_4}$$\end{document} sets. (shrink)

Adolescence is a developmental period characterized by intense changes, which impact the interaction between individuals and their environments. Moral reasoning is an important skill during adolescence because it guides social decisions between right and wrong. Identifying the cognitive underpinnings of MR is essential to understanding the development of this function. The aim of this study was to explore predictors of MR in typically developing adolescents and the specific contribution of higher order cognitive processing using an innovative visual MR assessment tool (...) and measures of executive functioning and intelligence. MR maturity was correlated with four executive functions and was predicted by four variables: age, intelligence, nonverbal flexibility and verbal fluency. Overall, these results contribute to a better understanding of MR during adolescence and highlight the importance of using innovative tools to measure social cognition. (shrink)

In this article, I try to go beyond the traditional objections to strict liability public welfare offenses and confront other possible justifications for punishing non-culpable conduct. Specifically, I consider the following arguments:Penalties for public welfare offenses are punishment by name only, thus traditional justifications for punishment are not needed;Even if those penalties are punishment, punishing those who produce or threaten significant harm to others is not necessarily unjust; andEven if such punishment is not entirely just, it is consistent with other (...) widely accepted criminal law doctrines. (shrink)

This paper is an exploration of Habermas’ critical reconstructions of the problematic of rationality via critical theory’s critique of instrumental reason. It brings together several key ideas ranging from the dialectic of instrumental reason and how it leads to epistemological dissonance to the discursive redemption of the normativity of reason. It sketches, as a concluding reflection, whether or not his ideas may be situated within the larger methodological trajectory of Philippine social science research. The paper thus considers the concepts of (...) discourse, discourse ethics and normative validity as crucially important. (shrink)

In 1924 the Fascist University was founded in Bologna. This essay reconstructs the foundation of this study centre, its cultural purposes and contacts with the academic world Giovanni Gentile had frequent relations with this cultural centre. On March 9th, 1930 he participated in a crowded lecture making a speech that was to remain unknown. It is published here and analyzed in relation to his complete works and the reactions aroused in Bologna and in the national cultural environments. The essay ends (...) with the circumstances that led to the closing of the Fascist University in 1933 and the consequences they caused. (shrink)