When seriously ill patients reach the end of the standard treatment trajectory for their condition, they may qualify for the use of unapproved, investigational drugs regulated via expanded access programs. In medical-ethical discourse, it is often argued that expanded access to investigational drugs raises ‘false hope’ among patients and is therefore undesirable. We set out to investigate what is meant by the false hope argument in this discourse. In this paper, we identify and analyze five versions of the false hope (...) argument which we call: (1) the limited chance at benefit argument, (2) the side effects outweighing benefits argument, (3) the opportunity costs argument, (4) the impossibility of making informed decisions argument, and (5) the difficulty of gaining access argument. We argue that the majority of these five versions do not provide normative ground for disqualifying patients’ hopes as false. Only when hope is rooted in a mistaken belief, for example, about the likelihood of benefits or chances on medical risks, or when hope is directed at something that cannot possibly be obtained, should it be considered false. If patients are adequately informed about their odds of obtaining medical benefit, however small, and about the risks associated with an investigational treatment, it is unjustified to consider patients’ hopes to be false, and hence, to deny them access to investigational drug based on that argument. (shrink)

Mimesis or imitation comes in many forms, from animal and plant mimicry to artistic copies 'from life'. This book offers eighteen essays addressing mimesis from diverse perspectives. From the recreation of galaxies to Iron Age torcs, from counterfeit dragons to modern waxworks, each chapter explores facets of material mimesis from prehistory to the present day. The Matter of Mimesis invites readers to compare practices of imitating, faking, and synthesising materials and objects in nature, art and science, raising questions about skills, (...) techniques and politics of making that transcend historical and disciplinary boundaries and inform both our past and future worlds. (shrink)

This paper examines the two main motifs in the Συναξάριον τοῦ τιμη- μένου γαδάρου and the Γαδάρου, λύκου κι ἀλουποῦς διήγησις ὡραία: the Ass’s Confession and the Mule’s Hoof, tracing them back to Medieval western rather than Ancient Aesopic sources. The Appendix deals with the dating and geographical provenance of the common ancestor of these two texts.

Drawing on ethical and legal frameworks in the Netherlands, the United States and France, we examine whether physicians are expected to inform patients about potentially relevant opportunities for expanded access to investigational drugs. While we found no definitive legal obligation, we argue that physicians have a moral obligation to discuss opportunities for expanded access with patients who have run out of treatment options to prevent inequality, to promote autonomy, and to achieve beneficence.

Trolling—the online exploitation of website, chat, or game mechanics at another user's expense—can and does take place all over cyberspace. It can take myriad forms, as well—some verbal, like trash-talking an opponent in a game, and some silent, like refusing to include a new player in a team effort during an in-game quest. However, despite this variety, there are few to no studies comparing the effects of these differing trolling types on victims. In addition, no study has yet taken into (...) account users' offline cultural context and norms into the trolling victim experience. To fill this gap in the literature, the present study put participants from three culturally-distinct countries—Pakistan, Taiwan, and the Netherlands—in a simulated trolling interaction using the Cyberball game. Participants were either flamed or ostracized by a member of their own cultural group or a minority member, and the participants' emotional responses, behavioral intentions toward the other players, and messages sent during the game were taken as indicators of their response to the trolling. Results showed that our Taiwanese sample used the most reactive aggression when trolled and our Dutch sample was the most passive. In addition, ostracism generally produced the desire to repair relationships, irrespective of cultural context, and perpetrator culture only produced an effect in the behavioral intentions of our Pakistani sample. Overall, it would appear that online and offline culture interact to produce the variety of responses to trolling seen in extant literature. Additional implications for future research into computer-mediated communication and online aggression are also discussed. (shrink)

This study traces the individual learning trajectories of an adult beginner L2 Finnish learner in expressing the extralinguistic concept of evaluation from a dynamic usage-based perspective. Our results provide support for the view of learner language as a dynamic system in which patterns wax and wane and in which a change in one component has the potential to affect the whole system. In the early stages of learning there was a strong preference to use lexical verbs first, and then adjectives. (...) The study also shows that variability plays a role. Finally, the study confirms that the learning of L2 constructions is in some cases item based. However, another highly frequent and superficially similar verbal construction in our data did not develop from a fixed formula. The role of instruction and the learner’s explicit knowledge as well as possibly input frequencies may have played a role in the different developmental trajectories. (shrink)

This study employed a scenario-based approach whereby participants were asked to choose which communication channel they prefer in certain situations. The first aim was to determine the effect of the topic of interactions and social ties on channel choice. The second aim was to examine the underlying mechanisms in the relation between interaction topic and social ties and channel choice. A questionnaire was administered among 238 participants, who were presented five communication scenarios with topics of low and high intimacy and (...) four social ties, ranging from weak to strong. Results revealed that preference for face-to-face communication was highest, followed by audio-only computer-mediated communication and text-based CMC. Preference for FtF communication was higher when people valued feeling co-present and decreased when people valued feeling anonymous. Our results showed that communication channel choice is strategic and the choice for FtF ommunication, audio-only and text-based CMC largely depends on controllability, anonymity and co-presence. (shrink)

Bulk collection involves the mining of large data sets containing personal data, often for a security purpose. In 2013, Edward Snowden exposed large scale bulk collection on the part of the US National Security Agency as part of a secret counter-terrorism effort. This effort has mainly been criticised for its invasion of privacy. I argue that the right moral argument against it is not so much to do with intrusion, as ineffectiveness for its official purpose and the lack (...) of oversight by security cleared legislators. It also lends itself to government "domination" (in Pettit's sense) of those who are subject to it. (shrink)

In earlier work, I have expressed scepticism about privacy-based criticisms of bulk collection for counter-terrorism ( Sorell 2018 ). But even if these criticisms are accepted, is bulk collection nonetheless legitimate on balance – because of its operational utility for the security services, and the overriding importance of the purposes that the security services serve? David Anderson’s report of the Bulk Powers review in the United Kingdom suggests as much, provided bulk collection complies with strong legal (...) safeguards ( Anderson 2016 ). I think it is hard to mount a uniformly compelling operational utility argument, because purposes other than counter-terrorism are pursued by the security services with the help of bulk collection. For example, the Intelligence Services Act 1994, section 1(2) says that apart from the interests of national security and the prevention and detection of serious crime, the Secret Intelligence Service may act “in the interests of the economic well-being of the United Kingdom.”The phrase “interests of the economic well-being of the United Kingdom” is opento a disturbingly wide range of interpretations, and it is doubtful that these interests justify bulk collection even when relevant “economic interests” are confined to those “also relevant to the interests of national security”, as required by the Investigatory Powers Act (2016) section 204 (3a). (shrink)

In a 1961 interview, Beckett warded off philosophical interpretations of his work: ‘I’m no intellectual. All I am is feeling’. Despite the emotional intensity of Beckett’s post-war writing, Beckett criticism has tended to ignore this claim, preferring the kinds of philosophical readings that Beckett here rejects. In particular, Beckett criticism underestimates the element of rage in his work. This paper argues that Beckett’s post-war breakthrough is enabled by a radical reconsideration of the nature of feeling and of rage in particular. (...) It involves the rejection of the idea of rage as pathological and the embrace of a positive conception of rage as drive or compulsion, a locus of energy and even pleasure.This paper reads the ‘Moran’ section of Molloy as a kind of ‘rage fable’, drawing on the ancient Greek concept of thymos, of anger as a virtue. It draws on Alfred Adler’s theory of the ‘masculine protest’, with which Beckett was familiar from his extensive note-taking on Adler in 1934-5, and Sianne Ngai’s discussion of the distinction between irritation and rage. According to this reading, Moran’s report charts a narrative of thymotic liberation from the irritations of servitude, prefiguring the Unnamable’s abandonment to impersonal affective intensities. It ends by suggesting that the prose of the Trilogy might be better understood, not as a ‘syntax of weakness’ but as a ‘syntax of rage’, a stylistic correlative of the imperious drive of thymos. We might then begin to understand the Trilogy as the epic of a heroic, impersonal, implacable and liberated rage. (shrink)

This paper is concerned with situations in which a speaker issues many speech acts at the same time. A common example is the publication of a large text such as a book containing many distinct assertions. It is argued that these cases present a challenge for speech act theory related to how we are to understand sincerity. With reference to the well known paradox of the preface, it is argued that sincerity of such bulk speech cannot be understood as (...) a simple conjunction of the sincerity of the encoded acts. A proposal is given according to which sincere bulk speech requires the speaker explicitly and as precisely as possible mark any subsets of her communication about which she has doubts. (shrink)

In his biography of Isaac Newton, which forms the most recent production in this flourishing genre, Niccolò Guicciardini states as his first point of departure that Newton's work arose not from ‘attempts to answer questions that came to him spontaneously, but [from addressing] those posed by his contemporaries’. Right he is to communicate to the larger audience for which he is writing this principal fruit of by now almost a century of professional history-of-science writing – a deep-seated awareness that every (...) scientific view or finding, even if looking timeless in retrospect, has emerged from some given historical context that shows us where the scientist in question started, and that helps explain how, and in what direction, they managed to venture beyond the original context. Indeed, the same truth applies to every genuine – that is, in some way innovative and also worthwhile – contribution to scholarship. And so it is, therefore, with the three books here under review, which I intend to examine with the following leading question in mind: what in each of them is new and what, in what turns out to be new indeed, has been worth learning? (shrink)

The evolution of microstructure upon partial crystallization and its influence on the mechanical properties such as hardness, elastic modulus and viscosity in a La 55 Al 25 Cu 10 Ni 5 Co 5 bulk metallic glass alloy are studied. Specimens with various volume fractions of crystalline phases were obtained by annealing the as-cast amorphous alloy above its glass transition temperature and were characterized by transmission electron microscopy. Microscopic examination of the heat-treated samples shows short-range-ordered domains prior to nanocrystallization within (...) the amorphous matrix, followed by the growth and impingement of the crystallites. Whereas the hardness of the annealed samples increases linearly with increasing crystallinity, the elastic modulus and the viscosity both increase abruptly when the crystalline volume fraction is about 40 vol.%, with a only minor variation on either side of this range. The sudden rises in the modulus and viscosity are similar to those in the literature data on the fracture strength of partially crystallized bulk amorphous alloys that shows a steep drop in strength at 30-50 vol.% crystallinity. On the basis of the microscopic observations, it is suggested that the interaction and formation of rigid networks of crystalline phases upon the attainment of a critical second-phase volume fraction may be the possible reason for the sudden change in mechanical properties. Percolation theory is utilized in further substantiating this hypothesis. (shrink)

In this paper, a fresh shear-displacement model is developed for the plastic deformation of the bulk metallic glasses. The multiscale behavior in the shear banding process and the dynamics transition with the parameters are investigated in analytical form. We present a theoretical support for the transition from unstable states to stable states in the experiment by multiscale analysis and the stability analysis. With the small parameter increasing from negative to positive, the stability of the shear slipping displacement system changes, (...) and there is a limit cycle at the transition stage. Meanwhile, the phase diagram and the power spectrum also suggest that there is dynamics transition with the parameter changing. Moreover, the complexity is analyzed for different disturbance parameters, and it is coincident with the fact that the solution is more irregular for larger disturbance. In addition, we find that the amplitude of solution decreases with the temperature decreasing, which is consistent with the experimental results that the amplitude of the serration is smaller and smaller as the temperature decreases. (shrink)

The chromatin‐regulatory principles of histone post‐translational modifications (PTMs) are discussed with a focus on the potential alterations in chromatin functional state due to steric and mechanical constraints imposed by bulky histone modifications such as ubiquitin and SUMO. In the classical view, PTMs operate as recruitment platforms for histone “readers,” and as determinants of chromatin array compaction. Alterations of histone charges by “small” chemical modifications (e.g., acetylation, phosphorylation) could regulate nucleosome spontaneous dynamics without globally affecting nucleosome structure. These fluctuations in nucleosome (...) wrapping can be exploited by chromatin‐processing machinery. In contrast, ubiquitin and SUMO are comparable in size to histones, and it seems logical that these PTMs could conflict with canonical nucleosome organization. An experimentally testable hypothesis that by adding sterical bulk these PTMs can robustly alter nucleosome primary structure is proposed. The model presented here stresses the diversity of mechanisms by which histone PTMs regulate chromatin dynamics, primary structure and, hence, functionality. (shrink)

The foundations of Wesson’s induced matter theory are analyzed. It is shown that the empty—without matter—5-dimensional bulk must be regarded as a Weylian space rather than as a Riemannian one. Revising the geometry of the bulk, we have assumed that a Weylian connection vector and a gauge function exist in addition to the metric tensor. The framework of a Weyl–Dirac version of Wesson’s theory is elaborated and discussed. In the 4-dimensional hypersurface (brane), one obtains equations describing both fields, (...) the gravitational and the electromagnetic. The result is a geometrically based unified theory of gravitation and electromagnetism with mass and current induced by the bulk. In special cases on obtains on the brane the equations of Einstein–Maxwell, or these of the original induced matter theory. (shrink)

Disputes at the intersection of national security, surveillance, civil liberties, and transparency are nothing new, but they have become a particularly prominent part of public discourse in the years since the attacks on the World Trade Center in September 2001. This is in part due to the dramatic nature of those attacks, in part based on significant legal developments after the attacks (classifying persons as “enemy combatants” outside the scope of traditional Geneva protections, legal memos by White House counsel providing (...) rationale for torture, the USA Patriot Act), and in part because of the rapid development of communications and computing technologies that enable both greater connectivity among people and the greater ability to collect information about those connections. -/- One important way in which these questions intersect is in the controversy surrounding bulk collection of telephone metadata by the U.S. National Security Agency. The bulk metadata program (the “metadata program” or “program”) involved court orders under section 215 of the USA Patriot Act requiring telecommunications companies to provide records about all calls the companies handled and the creation of database that the NSA could search. The program was revealed to the general public in June 2013 as part of the large document leak by Edward Snowden, a former contractor for the NSA. -/- A fair amount has been written about section 215 and the bulk metadata program. Much of the commentary has focused on three discrete issues. First is whether the program is legal; that is, does the program comport with the language of the statute and is it consistent with Fourth Amendment protections against unreasonable searches and seizures? Second is whether the program infringes privacy rights; that is, does bulk metadata collection diminish individual privacy in a way that rises to the level that it infringes persons’ rights to privacy? Third is whether the secrecy of the program is inconsistent with democratic accountability. After all, people in the general public only became aware of the metadata program via the Snowden leaks; absent those leaks, there would have not likely been the sort of political backlash and investigation necessary to provide some kind of accountability. -/- In this chapter I argue that we need to look at these not as discrete questions, but as intersecting ones. The metadata program is not simply a legal problem (though it is one); it is not simply a privacy problem (though it is one); and it is not simply a secrecy problem (though it is one). Instead, the importance of the metadata program is the way in which these problems intersect and reinforce one another. Specifically, I will argue that the intersection of the questions undermines the value of rights, and that this is a deeper and more far-reaching moral problem than each of the component questions. (shrink)

This article examines land-use changes by large-scale plantations in Ethiopia and evaluates the impacts thereof on soil organic carbon, micronutrients and bulk density. Remote sensing analysis and field research activities were undertaken at four large-scale plantation projects in Benshanguel Gumuz, Gambella, and Oromia regional states. Results show that the projects largely involved the conversion of both closed and open to closed forests and grasslands, which in turn reduced soil carbon stock and micronutrient levels and increased soil compaction. We argue (...) that unless appropriate soil management activities and impact mitigation strategies are adopted by plantation proponents, these land-use changes will pose a serious threat to the long-term economic viability and sustainability of plantation agriculture in Ethiopia. This could undermine long-term ecosystem health and national food security. (shrink)