The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or (...) activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

Objectives—To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Design—Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Results—Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only (...) seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Discussion—Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval. (shrink)

Reviewed work: The Eighteenth Century Confronts the Gods by Frank E. Manuel Historical Pessimism in the French Enlightenment by Henry Vyverberg.

Розкрито сутність поняття «рейтинг». Доведено значущість рейтингової оцінки для суб’єктів фінансового ринку, зокрема для страхових компаній, потенційних страхувальників, інвесторів та кредиторів.

This article asserts the significance of the portrayal of the political art of statesmanship as weaving, and aims to show how this image emphasizes two main aspects of the political art of statesmanship. Firstly, the image implies a three-dimensionality, both through the process of weaving and through the thickness of the protective fabric this produces, that in turn indicates the vital aspect of corporeality in politics. Secondly, weaving as a paradigmatic example of the art of statesmanship presents a way of (...) incorporating different entities and joining diverse threads into a cohesive unity, without reducing them to a form of sameness as mere mathematical counting would. These two aspects are in turn connected to an emphasis on the importance in good statesmanship of recognizing the specificity of the occasion and the variety and difference of the innumerable qualities to be interlaced in weaving the fabric of a good society. (shrink)

In his recent article entitled ‘Can We Believe the Error Theory?’ Bart Streumer argues that it is impossible (for anyone, anywhere) to believe the error theory. This might sound like a problem for the error theory, but Streumer argues that it is not. He argues that the un-believability of the error theory offers a way for error theorists to respond to several objections commonly made against the view. In this paper, we respond to Streumer’s arguments. In particular, in sections 2-4, (...) we offer several objections to Streumer’s argument for the claim that we cannot believe the error theory. In section 5, we argue that even if Streumer establishes that we cannot believe the error theory, this conclusion is not as helpful for error theorists as he takes it to be. (shrink)

A 16-year-old adolescent who identifies as transgender wishes to consider fertility preservation prior to the use of gender-affirming hormones. The adolescent’s parents are divorced, and one parent supports fertility preservation while the other does not. This case explores the minor’s future reproductive autonomy and parental decision making in a field where there is limited evidence of known harms and benefits to the use of fertility preservation in the transgender population and about future potential regret from lack of consideration of fertility (...) preservation during the prime window of opportunity. This case is created from a composite of cases seen at multiple institutions. (shrink)

In his recent book Error Theory: History, Critique, Defence, Jonas Olson attempts to revive the argument from queerness originally made famous by J.L. Mackie. In this paper, we do three things. First, we eliminate four untenable formulations of the argument. Second, we argue that the most plausible formulation is one that depends crucially upon considerations of parsimony. Finally, we evaluate this formulation of the argument. We conclude that it is unproblematic for proponents of moral non-naturalism—the target of the argument from (...) queerness. (shrink)

We provide a novel defense of the possibility of level-splitting beliefs and use this defense to show that the steadfast response to peer disagreement is not, as it is often claimed to be, unnecessarily dogmatic. To provide this defense, a neglected form of moral disagreement is analysed. Within the context of this particular kind of moral disagreement, a similarly neglected form of level-splitting belief is identified and then defended from critics of the rationality of level-splitting beliefs. The chapter concludes by (...) showing that proponents of the steadfast response to peer disagreement can adopt this form of level-splitting belief in the context of these moral disagreements while exemplifying intellectual humility, rather than dogmatism. (shrink)

Liao and Carbonell argue that medical devices are often not merely biased, but rather materialize oppression through the perpetuation of oppression into the present and future (Liao and Carbonell 2...

Numbers 25 presents a human crisis requiring swift leadership interventions to curb the plague. Leadership failure plays out on a number of levels before decisive and resolute interventions are taken. This passage shows a human-created crisis that somewhat parallels the coronavirus disease 2019 outbreak and offers reflective pragmatic approaches taken to ensure immediate arresting of the pandemic and perhaps future curbing of a similar instigation.CONTRIBUTION: Africa has always been known to respond rather belatedly to crises that cost human lives and (...) also for waiting for solutions to come from elsewhere. How do we change that paradigm going forward and what does it mean for the analysis of biblical texts? African hermeneutical readings that take contextual issues rather seriously are utilised in this study. (shrink)

Even though the concept of sustainability emerged from a reality-life emergency, its discourse seems diverse, built even on different onto-gnoseological and teleological assupmtions. This is mainly due to the different perceptions of life held by individuals, as well as to the hegemonic class interests. Then, derived from this different perceptions of life and interests, has been the behavior of human beings on the Earth; sometimes in accordance to it, but many others in outright aggression to it. And if life’s way (...) shows life itself, it can be changed, even collapsed by the anthropic hegemonic actions that take place in the planet. It is therefore important to reflect on the categorical and conceptual frameworks that underlie discourse, in order to build a way of thinking that includes all formas of life, that enhances the eco-existentiality of the individual and its community for the enrichment of all. (shrink)

As a 2006 Institute of Medicine report highlights, surprisingly little empirical attention has been paid to how prisoners arrive at decisions to participate in modern research. With our study, we aimed to fill this gap by identifying a more comprehensive range of factors as reported by prisoners themselves during semistructured interviews. Our participants described a diverse range of motives, both favoring and opposing their eventual decision to join. Many are well-recognized considerations among nonincarcerated clinical research participants, including a desire for (...) various forms of personal benefit, altruism, and concern about study risks and inconveniences. However, a number of influences seem unique to prisoners. Participants did not report that they were not coerced into enrolling, and they have even been under pressure not to enroll. However, many sought to enroll in order to obtain access to better health care, raising a concern about whether they were unfairly exploited. (shrink)

Privacy by Design, a globally accepted framework for personal data management and privacy protection, advances the view that privacy cannot be assured solely by compliance with regulatory frameworks but must become an organisation’s default mode of operation. We are proposing a similar template for the research ethics review process. The Research Ethics by Design framework involves research ethics committees engaging researchers during the design phase of the proposal so that ethical considerations may be directly embedded in the science as opposed (...) to being viewed as addendums after the fact. This collaborative research design proposal results in the establishment of a culture of ethical research rather than research with ethical oversight. Both researchers and research ethics committees come to view the review process as one in which individual protection and collective benefit co-exist in a doubly-enabling positive-sum manner. (shrink)

This book offers a critical introduction to the work of American philosopher D. G. Leahy (1937-2014). Leahy's fundamental thinking can be characterized as an absolute creativity in which all creating is 'live' -- a happening occurring now that manifests a supersaturated polyontological actuality that is essentially created by the logic that characterizes it. Leahy leaves behind the categorial presuppositions of modern thought, eclipsing both Cartesian and Hegelian subjectivities and introducing instead an essentially new form of thinking founded in a nondual (...) logic of creation. The new thinking delineates the absolute unicity of existence as a creative interactivity beyond all traditional dichotomies (such as one vs. many, unity vs. plurality, identity vs. change): a fully "digitized" actuality that is nothing but newness, which inherently implies nothing but change. Through this new form of thinking, change itself is revealed to be the very essence of reality and mind. Any reader looking for a quantum leap beyond the thrall of modern and postmodern fixations is invited to hear and apprehend this new thinking that refuses to be conditioned by paradigms, categories, species, genera, walls, bridges, boundaries, or abstractions: an essentially free thinking that embodies creative novelty itself. (shrink)

Moorean arguments are a popular and powerful way to engage highly revisionary philosophical views, such as nihilism about motion, time, truth, consciousness, causation, and various kinds of skepticism (e.g., external world, other minds, inductive, global). They take, as a premise, a highly plausible first-order claim (e.g., cars move, I ate breakfast before lunch, it’s true that some fish have gills) and conclude from it the falsity of the highly revisionary philosophical thesis. Moorean arguments can be used against nihilists in ethics (...) (error theorists), too. Recently, error theorists have recognized Moorean arguments as a powerful challenge and have tried to meet it. They’ve argued that moral Moorean premises seem highly credible to us, but aren’t, by offering various debunking explanations. These explanations all appeal to higher-order evidence—evidence of error in our reasoning. I argue that drawing attention to higher-order evidence is a welcome contribution from error theorists, but that the higher-order evidence actually counts further against error theoretic arguments—including their debunking explanations—and further in favor of Moorean arguments and the commonsense views they support. Along the way I answer a few prominent objections to Moorean arguments: that they are objectionably question-begging, rely on categorizing some facts as “Moorean Facts”, and that reports of one’s credence in a proposition bears no interesting relation to that proposition’s credibility. (shrink)

Arguments from disagreement against moral realism begin by calling attention to widespread, fundamental moral disagreement among a certain group of people. Then, some skeptical or anti-realist-friendly conclusion is drawn. Chapter 2 proposes that arguments from disagreement share a structure that makes them vulnerable to a single, powerful objection: they self-undermine. For each formulation of the argument from disagreement, at least one of its premises casts doubt either on itself or on one of the other premises. On reflection, this shouldn’t be (...) surprising. These arguments are intended to support very strong metaphysical or epistemological conclusions about morality. They must therefore employ very strong metaphysical or epistemological premises. But, given the pervasiveness of disagreement in philosophy, especially about metaphysics and epistemology, very strong premises are virtually certain to be the subject of widespread, intractable disagreement—precisely the sort of disagreement that proponents of these arguments think undermine moral claims. Thus, these arguments undermine their own premises. If Chapter 2’s argument is sound, it provides realists with a single, unified strategy for responding to any existing or forthcoming arguments from disagreement. (shrink)