Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

In an increasingly complex military operating environment, next generation wargaming platforms can reduce risk, decrease operating costs, and improve overall outcomes. Novel Artificial Intelligence enabled wargaming approaches, based on software platforms with multimodal interaction and visualization capacity, are essential to provide the decision-making flexibility and adaptability required to meet current and emerging realities of warfighting. We highlight three areas of development for future warfighter-machine interfaces: AI-directed decisional guidance, computationally informed decision-making, and realistic representations of decision spaces. Progress in these areas (...) will enable development of effective human-AI collaborative decision-making, to meet the increasing scale and complexity of today’s battlespace. (shrink)

E. L. Mascall; XIV—Perception and Sensation, Proceedings of the Aristotelian Society, Volume 64, Issue 1, 1 June 1964, Pages 259–272, https://doi.org/10.1093/ar.

E. L. Mascall; XIV—Perception and Sensation, Proceedings of the Aristotelian Society, Volume 64, Issue 1, 1 June 1964, Pages 259–272, https://doi.org/10.1093/ar.

The word ‘existentialism’ has become something of a catchword in religious circles today, and one suspects that it is sometimes a substitute rather than a medium for thought. Most theological teachers must from time to time have received from a pupil an essay in which the words ‘existential’, ‘existentially’ and ‘existentialism’ appear to have been sprinkled from a pepper-pot over an exposition whose meaning would remain unchanged if these words were excised altogether. Nevertheless, usum non tollit abusus, and the following (...) rather unsystematic remarks may perhaps be of some help in elucidating and evaluating a mode of thought and expression which has attracted the interest of some of the more profound, as well as of some of the more superficial, theological and philosophical writers of the present day. (shrink)

Research Ethics Committees (RECs) are frequently a focus of complaints from researchers, but evidence about the operation and decisions of RECs tends to be anecdotal. We conducted a systematic study to identify and compare the ethical issues raised in 54 letters to researchers about the same 18 applications submitted to three RECs over one year. The most common type of ethical trouble identified in REC letters related to informed consent, followed by scientific design and conduct, care and protection of research (...) participants, confidentiality, recruitment and documentation. Community considerations were least frequently raised. There was evidence of variability in the ethical troubles identified and the remedies recommended. This analysis suggests that some principles may be more institutionalized than others, and offers some evidence of inconsistency between RECs. Inconsistency is often treated as evidence of incompetence and caprice, but a more sophisticated understanding of the role of RECs and their functioning is required. (shrink)

Medical educators invoke professionalism as a core competency in curricula. This paper criticizes classic definitions. It also identifies some negative traits of medicine as a profession. The call to professionalism is naive nostalgia. Straightforward didactics in professionalism cannot do the desired work in medical education. The most we can say is that students should adopt the good aspects of professionalism and the profession should stop being some of what it has been. This is a platitude. If the notion is to (...) be more than shallow, each student and practitioner will have to engage in much dialogue, reflection and refinement over many years. (shrink)