We discuss a case where clinical genomic investigation of muscle weakness unexpectedly found a genetic variant that might (or might not) predispose to kidney cancer. We argue that despite its off-target and uncertain nature, this variant should be discussed with the man who had the test, not because it is medical information, but because this discussion would allow the further clinical evaluation that might lead it to becoming so. We argue that while prominent ethical debates around genomics often take ‘results’ (...) as a starting point and ask questions as to whether to look for and how to react to them, the construction of genomic results is fraught with ethical complexity, although often couched as a primarily technical problem. We highlight the need for greater focus on, and appreciation of, the ethical work undertaken daily by scientists and clinicians working in genomic medicine and discuss how public conversations around genomics need to adapt to prepare future patients for potentially uncertain and unexpected outcomes from clinical genomic tests. (shrink)

All languages, both spoken and signed, make a formal distinction between two types of terms in a proposition – terms that identify what is to be talked about (nominals) and terms that say something about this topic (predicates). Here we explore conditions that could lead to this property by charting its development in a newly emerging language – Nicaraguan Sign Language (NSL). We examine how handshape is used in nominals vs. predicates in three Nicaraguan groups: (1) homesigners who are not (...) part of the Deaf com- munity and use their own gestures, called homesigns, to communicate; (2) NSL cohort 1 signers who fashioned the first stage of NSL; (3) NSL cohort 2 signers who learned NSL from cohort 1. We compare these three groups to a fourth: (4) native signers of American Sign Language (ASL), an established sign language. We focus on handshape in predicates that are part of a productive classifier system in ASL; handshape in these predicates varies sys- tematically across agent vs. no-agent contexts, unlike handshape in the nominals we study, which does not vary across these contexts. We found that all four groups, including home- signers, used handshape differently in nominals vs. predicates – they displayed variability in handshape form across agent vs. no-agent contexts in predicates, but not in nominals. Variability thus differed in predicates and nominals: (1) In predicates, the variability across grammatical contexts (agent vs. no-agent) was systematic in all four groups, suggesting that handshape functioned as a productive morphological marker on predicate signs, even in homesign. This grammatical use of handshape can thus appear in the earliest stages of an emerging language. (2) In nominals, there was no variability across grammatical con- texts (agent vs. no-agent), but there was variability within- and across-individuals in the handshape used in the nominal for a particular object. This variability was striking in homesigners (an individual homesigner did not necessarily use the same handshape in every nominal he produced for a particular object), but decreased in the first cohort of NSL and remained relatively constant in the second cohort. Stability in the lexical use of handshape in nominals thus does not seem to emerge unless there is pressure from a peer linguistic community. Taken together, our findings argue that a community of users is essential to arrive at a stable nominal lexicon, but not to establish a productive morpholog- ical marker in predicates. Examining the steps a manual communication system takes as it moves toward becoming a fully-fledged language offers a unique window onto factors that have made human language what it is. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Do cultural models facilitate particular ways of perceiving interactions in nature? We explore variability in folkecological principles of reasoning about interspecies interactions. In two studies, Indigenous Panamanian Ngöbe and U.S. participants interpreted an illustrated, wordless nonfiction book about the hunting relationship between a coyote and badger. Across both studies, the majority of Ngöbe interpreted the hunting relationship as cooperative and the majority of U.S. participants as competitive. Study 2 showed that this pattern may reflect different beliefs about, and perhaps different (...) awareness of, plausible interspecies interactions. Further probes suggest that these models of ecological interaction correlate with recognition of social agency in nonhuman animals. We interpret our results in terms of cultural models of nature and nonhuman agency. (shrink)

It's not about any person who's going to pick it up. No, these addresses fix on a much more glorious, worthy, and fascinating topic: the God, the Creator, the Redeemer as revealed in the Bible. The study of God is like a brilliant diamondwe should keep holding it up to the light to see new details ofits beauty. Before the awe of such a God, what room is there to focus on man? Our only place is to respond to himand (...) even our response does not depend on us! We must not only worship him, but alsoif our worship is to be meaningful and not cheapenedlearn how he is to be worshiped. The Princeton Regional Conference on Reformed Theology presents the following pastor-scholars, who delve into the glory of God and into his grace in making sinners into worshipers: Bryan Chapell - God's Glory Revealed Charles D. Drew - Called by God to Worship Richard D. Phillips - Sought by Christ to Worship Joseph "Skip" Ryan - Guided by God's Sovereign Providence Philip Graham Ryken - Redeemed by God's Sovereign Mercy Michael S. Horton - Sanctifying Grace Richard D. Phillips - Our Holy Redeemer Michael A. G. Haykin - The Spirit of Holiness R. Albert Mohler - Know the Truth D. A. Carson -I Am the Truth Learn from these teachers about the glory of, the providential work of, and our proper response to the amazing God we worship. (shrink)

The content of dreams and changes to the self were investigated in students moving to University. In study 1, 20 participants completed dream diaries and memory tasks before and after they had left home and moved to university, and generated self images, “I am…” statements , reflective of their current self. Changes in “I ams” were observed, indicating a newly-formed ‘university’ self. These self, images and related autobiographical knowledge were found to be incorporated into recent dreams but not into dreams (...) from other periods. Study 2 replicated these findings in a different sample . We suggest that these data reflect a period of self-consolidation in which new experiences and self images are incorporated into autobiographical memory knowledge structures representing personal goals during sleep. (shrink)

Before September 11, 2001, a mass-casualty terrorist attack on American soil was generally considered a remote possibility. Similarly, before October 4, 2001—the first confirmed case of anthrax caused by intentional release — widespread bioterrorism seemed implausible. Among the arguments that such a biological artack was unlikely included: the lack of a historical precedent; the technological and organizational challenges to acquiring and weaponizing a biological agent; and the almost universal moral opprobrium that would certainly accompany the use by terrorists of such (...) a weapon. In the wake of September 11th and October 4th, however, many are reconsidering the likelihood of a large-scale bioterrorist attack against civilians.The Centers for Disease Control and Prevention defines bioterrorism as the intentional release of viruses, bacteria, or toxins for the purpose of harming or killing civilian. One measurement of the public health system's level of bioterrorism preparedness is the quality and distribution of laws mandating the reporting of diseases caused by certain biological agents. (shrink)

This article examines Kamel Daoud’s treatment of solidarity and the absurd in Meursault, contre-enquête and posits that the question of how to live in solidarity with others is central to the novel, although the word ‘solidarity’ never appears in it. After recalling Camus’s discussion of the absurd in Le Mythe de Sisyphe and of solidarity in L’Homme révolté, the article examines the manner in which Haroun, Daoud’s narrator and the brother of the Arab Meursault killed in L’Étranger, reveals his own (...) failures of solidarity. He justly criticizes Meursault for privileging his confrontation with the absurd over the death of the Arab he did not even name, but Haroun too has killed. Haroun has, however, a greater understanding of solidarity than his fellows: he at least recognizes that murder is significant. He thus joins Meursault as an unworthy prophet who proclaims the absurd while surrounded by people who flee from it—and proclaiming the absurd can be a gesture of solidarity when one speaks for others, as Haroun speaks for his brother Moussa. Daoud’s novel reminds us that there are no final answers telling us how to live in solidarity with others and that we must do so all the same. (shrink)

Translation (French to English) of Pierre Drouot's "Reconnaissance et hospitalité – Retour sur le retour d’Ulysse.".

Translation (French to English) of Jean-Luc Nancy's "L'Annoncée.".

David Blank presents a new translation into clear modern English of a key treatise by one of the greatest of ancient philosophers, together with the first ever commentary on this work. Sextus Empiricus' Against the Grammarians is a polemical attack on ancient Greek ideas about grammar, and provides one of the best examples of sustained Sceptical reasoning.

The history of the National Health Service research ethics system in the UK and some of the key drivers for its change into the present system are described. It is suggested that the key drivers were the unnecessary delay of research, the complexity of the array of processes and contradictions between research ethics committee (REC) decisions. It is then argued that the primary drivers for this change are and will be replicated by the systems of research ethics review being put (...) in place at UK universities in response to the Economic and Social Research Council research ethics framework. It is argued that this is particularly problematic for multi-centre review and for researchers who switch institutions. Finally, some potential solutions to this problem and their feasibility are discussed. (shrink)

There has been a troublesome anomaly in the UK between cash payment to men for sperm donation and the effective assumption that women will pay to donate eggs. Some commentators, including Donald Evans in this journal, have argued that the anomaly should be resolved by treating women on the same terms as men. But this argument ignores important difficulties about property in the body, particularly in relation to gametes. There are good reasons for thinking that the contract model and payment (...) for gametes are both inappropriate, and that a model based on altruism should be applied to both sexes. (shrink)