We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

In three studies, factors influencing the incidence of fraudulent financial reporting were assessed. We examined (1) the effects of personal values and (2) codes of corporate conduct, on whether managers misrepresented financial reports. In these studies, executives and controllers were asked to respond to hypothetical situations involving fraudulent financial reporting procedures. The occurrence of fraudulent reporting was found to be high; however, neither personal values, codes of conduct, nor the interaction of the two factors played a significant role in fraudulent (...) financial reporting. (shrink)

In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social (...) sciences using a pre–post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. (shrink)

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

The inconsistent definition of empathy has had a negative impact on both research and practice. The aim of this article is to review and critically appraise a range of definitions of empathy and, through considered analysis, to develop a new conceptualisation. From the examination of 43 discrete definitions, 8 themes relating to the nature of empathy emerged: “distinguishing empathy from other concepts”; “cognitive or affective?”; “congruent or incongruent?”; “subject to other stimuli?”; “self/other distinction or merging?”; “trait or state influences?”; “has (...) a behavioural outcome?”; and “automatic or controlled?” The relevance and validity of each theme is assessed and a new conceptualisation of empathy is offered. The benefits of employing a more consistent and complete definition of empathy are discussed. (shrink)

The American Journal of Bioethics, Volume 12, Issue 10, Page 9-10, October 2012.

Background Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent. Objectives To explore what people want in a surrogate decision-maker whom they themselves select and to test the assumption that people want their chosen surrogate to make only a substituted judgement. Methods 30 undergraduate students were recruited. They were presented with a hypothetical scenario about their expected loss of mental capacity in (...) the future and asked to answer some questions about their choice of surrogate. These data were analysed qualitatively using thematic content analysis. Results Most respondents talked about choosing someone who was caring and competent in certain ways, giving interesting evidence for their judgements. Surprisingly few highlighted how well they thought their chosen surrogate knew their preferences and would be able to make a substituted judgement. Moreover, few specified that their chosen surrogate had similar attitudes and values to their own and so would make a similar decision to theirs in the circumstances presented. Some respondents also referred to the social role of their chosen surrogate or the social dynamics of their situation which influenced their choices, as well as to ideas of reciprocity and characteristics of honesty and loyalty. Conclusion In the event that they lose mental capacity, many people will not select a surrogate to decide about medical treatments on their behalf solely on the basis that they expect their surrogate to make a substituted judgement. (shrink)

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert Advisory Group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since (...) the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs Programme. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating and integrating evidence to identify causes of human cancer. The advancements adopted include strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention. (shrink)

Background While prenatal surgery historically was performed exclusively for lethal conditions, today intrauterine surgery is also performed to decrease postnatal disabilities for non-lethal conditions. We sought to describe physicians' attitudes about prenatal surgery for lethal and non-lethal conditions and to elucidate characteristics associated with these attitudes. Methods Survey of 1200 paediatric surgeons, neonatologists and maternal–fetal medicine specialists. Results Of 1176 eligible physicians, 670 responded. In the setting of a lethal condition for which prenatal surgery would likely result in the child (...) surviving with a severe disability, most respondents either disagreed or strongly disagreed that they would recommend the surgery. Male physicians were twice as likely to recommend surgery for the lethal condition, as were physicians who believe that abortion is morally wrong. Older physicians were less likely to recommend surgery. For non-lethal conditions, most respondents agreed that they would recommend prenatal surgery, even if the surgery increases the risk of prematurity or fetal death. Compared with MFMs, surgeons were less likely to recommend such surgery, as were physicians not affiliated with a fetal centre, and physicians who were religious. Conclusion Physician’s attitudes about prenatal surgery relate to physicians’ beliefs about disability as well as demographic, cultural and religious characteristics. Given the variety of views, parents are likely to receive different recommendations from their doctors about the preferable treatment choice. (shrink)

In his article ‘Did the Athenians Regard Seduction as a Worse Crime than Rape?’, CQ 40, 370–7, Edward M. Harris rightly casts doubt on the value of Lysias 1.30–5, which has generally been accepted as evidence that the Athenians did indeed regard seduction as the worse of the two crimes. Euphiletos in this speech is defending himself on a charge of murder, and, as Harris says, ‘Euphiletus’ presentation of the Athenian statutes regarding rape and seduction is dictated by the rhetorical (...) constraints of his case. It is not a reflection of widely held social attitudes.'. (shrink)

This chapter describes the potential far‐reaching consequences of contemplative higher education for the fields of science and medicine.

We define the notion of a completely determined Borel code in reverse mathematics, and consider the principle $CD - PB$, which states that every completely determined Borel set has the property of Baire. We show that this principle is strictly weaker than $AT{R_0}$. Any ω-model of $CD - PB$ must be closed under hyperarithmetic reduction, but $CD - PB$ is not a theory of hyperarithmetic analysis. We show that whenever $M \subseteq {2^\omega }$ is the second-order part of an ω-model (...) of $CD - PB$, then for every $Z \in M$, there is a $G \in M$ such that G is ${\rm{\Delta }}_1^1$-generic relative to Z. (shrink)

‘Menander has set up a confrontation between this law [the law about epikleroi] and love… He wants the audience to regard the law as stupid and wrong… Surely one of Menander's purposes in writing this play was to make the Athenians consider seriously whether the law ought to be changed.’ Thus Professor D. M. MacDowell in the concluding paragraph of his article ‘Love versus the Law: an Essay on Menander's Aspis’. A similar view was already implicit in E. Karabelias' treatment (...) of the play as indicative of the general attitude to this law in Athens in Menander's day: ‘A n'en point douter, l'épiclérat est ressenti, á l'epoque de Ménandre, comme une anomalie intolérable pour les mceurs de la societe athénienne à la fin du ive s.av.n.è L'épiclérat est odieux et ridicule… L'hostilité envers l'épiclérat est done un signe des temps’. And Professor E. G. Turner has written: ‘it is hard to imagine that the institution of the epiclerate emerged in good standing from this derisory treatment’. (shrink)

Scapula mobility complicates upper extremity kinematics assessment. Existing methods are diverse, providing inconsistent results. The current gold standard (bone pins) is prohibitively invasive. The purposes of the current study are to describe a virtual projection alternative to surface markers for video motion capture (VMC) of the scapula and to compare the results of the projection and surface marker methods to the results of similar existing methods. Ten participants were evaluated using VMC. Surface markers were applied to the trunk and arm (...) in accordance with existing guidelines. Three markers were affixed to plastic base on the skin over the acromion process. Other scapular landmarks were digitized in a neutral position. These landmarks’ locations were defined in reference to the acromion cluster and used to generate the projection. Humerothoracic, glenohumeral, and scapulothoracic kinematics were evaluated during shoulder abduction, flexion, and scaption. Joint angles produced by the surface markers and the projection were compared by Bonferroni-adjusted t tests. The results were compared to prior findings in the literature. The projection resulted in greater scapulothoracic upward rotation, internal rotation, and anterior–posterior tilt and less glenohumeral elevation (p <.0055) than did surface markers. The virtual scapula produced greater estimates of scapular mobility than did surface markers, corresponding to pre-existing results from similar methodologies. The result is a noninvasive measurement tool that produces different and superior results than do scapula surface markers. Measuring scapula kinematics via VMC without bone pins will facilitate future investigations into interactions between upper extremity injury, kinematics, and activity performance. (shrink)

‘Menander has set up a confrontation between this law [the law about epikleroi] and love… He wants the audience to regard the law as stupid and wrong… Surely one of Menander's purposes in writing this play was to make the Athenians consider seriously whether the law ought to be changed.’ Thus Professor D. M. MacDowell in the concluding paragraph of his article ‘Love versus the Law: an Essay on Menander's Aspis’. A similar view was already implicit in E. Karabelias' treatment (...) of the play as indicative of the general attitude to this law in Athens in Menander's day: ‘A n'en point douter, l'épiclérat est ressenti, á l'epoque de Ménandre, comme une anomalie intolérable pour les mceurs de la societe athénienne à la fin du ive s.av.n.è L'épiclérat est odieux et ridicule… L'hostilité envers l'épiclérat est done un signe des temps’. And Professor E. G. Turner has written: ‘it is hard to imagine that the institution of the epiclerate emerged in good standing from this derisory treatment’. (shrink)

In his article ‘Did the Athenians Regard Seduction as a Worse Crime than Rape?’, CQ 40 , 370–7, Edward M. Harris rightly casts doubt on the value of Lysias 1.30–5, which has generally been accepted as evidence that the Athenians did indeed regard seduction as the worse of the two crimes. Euphiletos in this speech is defending himself on a charge of murder, and, as Harris says , ‘Euphiletus’ presentation of the Athenian statutes regarding rape and seduction is dictated by (...) the rhetorical constraints of his case. It is not a reflection of widely held social attitudes.'. (shrink)