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)

When healthcare professionals feel constrained from acting in a patient’s best interests, moral distress ensues. The resulting negative sequelae of burnout, poor retention rates, and ultimately poor patient care are well recognized across healthcare providers. Yet an appreciation of how particular disciplines, including physicians, come to be “constrained” in their actions is still lacking. This paper will examine how the application of shared decision-making may contribute to the experience of moral distress for physicians and why such distress may go under-recognized. (...) Appreciation of these dynamics may assist in cross-discipline sensitivity, enabling more constructive dialogue and collaboration. (shrink)

“Recognizing that prisons disproportionately confine sick people, with mental illness, substance abuse, HIV disease among other illnesses; and that prisoners are subject to further morbidity and mortality in these institutions, due to lack of access and/or resources for health care, overcrowding, violence, emotional deprivation, and suicide.… condemns the social practice of mass imprisonment.”After decades of steady decline, tuberculosis has emerged as a significant public health threat in the United States. The rising rates of tuberculosis cases, an increasing proportion of which (...) are resistant to standard chemotherapies, are linked to the many scourges threatening our communities: the explosion of poverty, drug use, violence, the HIV epidemic, and the concomitant rise in congregate housing including homeless shelters, residential drug treatment programs and incarceration facilities. Jails and prisons have disproportionately high rates of tuberculosis infection and have been implicated as points of tuberculosis spread and, as such, are a critical point for tuberculosis control interventions. (shrink)

John Stuart Mill worked for the East India Company in London for thirty-five years (1823-58), drafting many hundreds of dispatches for the guidance of British administrators in India. Historians have long been aware of Mill's involvement in British Indian government. This comprehensive effort brings together different strands of scholarship on Mill to determine the character of his role based on analyses of his draft despatches and comparisons of their practical and theoretical concerns with the broad themes of Mill's major writings (...) on political philosophy and economics. The essays in this collection explore specific aspects of Mill's approach to Indian issues, including religion, law, education, and security, and also place him within the broader currents of utilitarianism. The contributors present different perspectives on the ideology in Mill's pragmatic work for the Company and his personal philosophy. (shrink)

The upcoming U.S. Supreme Court decision in Dobbs v. Jackson Women’s Health Organization has the potential to eliminate or severely restrict access to legal abortion care in the United States. We a...

A longitudinal study of 308 white -collar U.S. employees revealed that feelings of hope and gratitude increase concern for corporate social responsibility. In particular, employees with stronger hope and gratitude were found to have a greater sense of responsibility toward employee and societal issues; interestingly, employee hope and gratitude did not affect sense of responsibility toward economic and safety/quality issues. These findings offer an extension of research by Giacalone, Paul, and Jurkiewicz.

The ideal introduction for students of semantics, Lexical Meaning fills the gap left by more general semantics textbooks, providing the teacher and the student with insights into word meaning beyond the traditional overviews of lexical relations. The book explores the relationship between word meanings and syntax and semantics more generally. It provides a balanced overview of the main theoretical approaches, along with a lucid explanation of their relative strengths and weaknesses. After covering the main topics in lexical meaning, such as (...) polysemy and sense relations, the textbook surveys the types of meanings represented by different word classes. It explains abstract concepts in clear language, using a wide range of examples, and includes linguistic puzzles in each chapter to encourage the student to practise using the concepts. 'Adopt-a-Word' exercises give students the chance to research a particular word, building a portfolio of specialist work on a single word. (shrink)

This book explores how some word meanings are paradigmatically related to each other, for example, as opposites or synonyms, and how they relate to the mental organization of our vocabularies. Traditional approaches claim that such relationships are part of our lexical knowledge (our "dictionary" of mentally stored words) but Lynne Murphy argues that lexical relationships actually constitute our "metalinguistic" knowledge. The book draws on a century of previous research, including word association experiments, child language, and the use of synonyms and (...) antonyms in text. (shrink)

One cue that may facilitate children's word learning is iconicity, or the correspondence between a word's form and meaning. Some have even proposed that iconicity in the early lexicon may serve to help children learn how to learn words, supporting the acquisition of even noniconic, or arbitrary, word–referent associations. However, this proposal remains untested. Here, we investigate the iconicity of caregivers’ speech to young children during a naturalistic free‐play session with novel stimuli and ask whether the iconicity of caregivers’ speech (...) facilitates children's learning of the noniconic novel names of those stimuli. Thirty‐four 1.5‐2‐year‐olds (19 girls; half monolingual English learners and half bilingual English‐Spanish learners) participated in a naturalistic free‐play task with their caregivers followed by a test of word‐referent retention. We found that caregivers’ use of iconicity, particularly in utterances in which they named the novel stimuli, was associated with the likelihood that children learned that novel name. This result held even when controlling for other factors associated with word learning, such as the concreteness and frequency of words in caregiver speech. Together, the results demonstrate that iconicity not only can serve to help children identify the referent of novel words (as in previous research) but can also support their ability to retain even noniconic word‐referent mappings. (shrink)

Perhaps I am wrong to take this article personally, but when the authors refer to Cassandras “voicing concern about a post-Roe degradation of pregnant persons’ right to chart their own medical cour...

The editor of this volume takes it to mean that a prior experience affects behavior without the individual's appreciation (ability to report) of this...

Democratically inspired critics identify a number of problems with the contemporaryidentification of survey research and public opinion. Surveys are said tonormalize or rationalize opinion, to promote state or corporate rather thandemocratic interests, to constrain authentic forms of participation, and to forcean individualized conception of public opinion. Some of these criticisms arerelatively easily answered by survey researchers. But the criticisms contain acomplaint that survey researchers have largely failed to address: that surveyresearch discourages the public, visible, and face-to-face generation of opinion.Public opinion (...) researchers who use surveys paradoxically seek the opinions ofcitizens in private, nonpolitical situations. But nothing inherent in the methodsof survey research requires this private focus. The author argues that by reframingthe survey's unit of analysis and considering alternatives to standard,national samples in political surveys, new democratic possibilities within surveyresearch may be found. (shrink)

For many years, there has been a gap in our capacity to study the structure and organization of chromosomal DNA molecules. The very small genomes of some viruses and bacteriophages (≤ 50,000 bp or 50 kb) are amenable to analysis by conventional gel electrophoresis, while the extremely large DNA molecules (> 100,000 kb) comprising the chromosomes of higher eukaryotes have been analysed under the light microscope, using a range of banding and in situ hybridization techniques. However, intact DNA molecules with (...) sizes between these two extremes have been largely inaccessible experimentally. This gap has recently been bridged with the development of two‐dimensional electrophoretic procedures that allow the separation and purification of chromosome‐sized DNA molecules ranging from ∼ 50 kb to several thousand kb.1–3 There are currently two variations of the technique in use: pulsed field gradient (PFG) gel electrophoresis1,2 and orthogonal‐field‐alteration gel electrophoresis (OFAGE).3 Both are based on a common principle, differing primarily in the geometry of the electrodes. Already, they have been employed to determine the approximate chromosome sizes and numbers for a variety of lower eukaryotes, including yeast and several protozoa.2–10 These ‘molecular karyotypes’ provide fundamental information about the genomic organization of each organism, and allow very rapid construction of linkage maps. Surprisingly, they have also revealed a remarkable plasticity in the genomes of several lower eukaryotes. (shrink)

This essay critiques feminist treatments of maternal-fetal "relationality" that unwittingly replicate features of Western individualism (for example, the Cartesian division between the asocial body and the social-cognitive person, or the conflation of social and biological birth). I argue for a more reflexive perspective on relationality that would acknowledge how we produce persons through our actions and rhetoric. Personhood and relationality can be better analyzed as dynamic, negotiated qualities realized through social practice.

SummaryQuine uses the notion of ‘quality space’ in Word and Object and in ‘Natural Kinds' as a means of characterizing similarity recognition, which in turn is seen as basic to induction and to language acquisition. In this paper it is argued that ‘quality space’ is too simplistic a notion to bear the explanatory weight given to ‘similarity’. Similarity is explanatorily plausible only because it contains much covert complexity and is essentially mentalistic. The attempt to expunge this mentalism by the behavioural (...) mapping of quality spaces simply loses the explanatory force of similarity.RésuméQuine utilise dans ≤Word and Object≥ et dans ≤Natural Kinds≥ la notion ?on; ≤espace des qualityés≥ comme une façon de caractériser la reconnaissance de la similitude, qui est à son tour considérée comme fondamentale pour ľinduction ct pour ľacquisition du langage. auteur montre que la notion ?on; ≤cspace des qualityés≥ est trop simpliste pour fournir une base suffisante à la valeur explicative attendue de la ≤similitude≥. La similitude ňest plausible comme explication que parce qu'elle cache une grande complexité et čest une notion essentiellement mentale. La tentative de remplacer ce mentalisme par une projection behavioriste sur ľespace des qualites fait perdre à la similitude sa valeur explicative.ZusammenfassungIn ≤Word and Object≥ und in ≤Natural Kinds≥ benutzt Quine den Begriff ≤Eigenschafts‐raum≥ als Mittel um die Wahrnehmung der Ähnlichkeit zu charakterisieren, welche ihrerseits als grundlegend für Induktion und Aneignung der Sprache betrachtet wird. In der vorliegenden Arbeit wird argumentiert, dass dieser ≤Eigenschaftsraum≥ zu arm ist, um den Erklärungsgehalt des Begriffs ≤Ähnlichkeit≥ zu tragen. Die Erklärung durch Ähnlichkeit ist nur deshalb plausibel, weil sie versteckte Komplexität enthält und wesentlich mentalistisch ist. Bei dem Versuch, diesem Men‐talismus mithilfe der behavioristischen Abbildung der Eigenschäftsraume auszuweichen, geht die Erklärungskraft des Begriffs der Ähnlichkeit einfach verloren. (shrink)

We have conducted a retrospective study of deaths on a paediatric medical intensive care unit over a two-year period and reviewed similar series from outside the UK. There were 89 deaths out of 651 admission (13.7% mortality). In almost two-thirds of the cases death occurred with a decision to limit medical treatment or withdraw mechanical ventilation, implying that additional or further therapy was considered futile. We highlight this as a crucially important issue in the practice of intensive care. More comprehensive (...) studies are needed to help clinicians derive consensus on what constitutes a futile intervention, and therefore when such an intervention should be withheld. This will help families and society better understand the limitations of intensive care. (shrink)

The idea of “postponed withholding,” proposed by Syltern et al. (2022), is a provocative one, and like all good provocative ideas, provokes deeper thinking from fresh perspectives. Our attention wa...

The main goal of this study was to identify factors motivating pragmatic transfer in advanced learners of English. Based on a cross-cultural comparison of requesting behavior between Koreans and Americans, this study determined the impact of individual subjective motives on pragmatic language choice. Two different groups of subjects participated in this study: 30 Korean participants and 30 American college students. Data were collected by using a Discourse Completion Task. Korean participants provided the data for Korean and English versions of DCT. (...) Semi-structured interviews were also conducted with 13 Korean ESL learners who showed the most and least amount of pragmatic transfer. Findings showed evidence of pragmatic transfer in the request responses given by Korean ESL learners in their requestive strategies, level of directness, and perspectives of head acts. The interview data revealed that Korean students were conscious of differing rules for making requests. Learners’ judgment of L2 pragmatic norms, perception of their own language, and their attitudes of the target language influence language use. Furthermore, findings showed that purpose of learning English, different types of motivation, and the length of intended residence contribute to the extent of pragmatic transfer. (shrink)

When a caregiver names objects dominating a child’s view, the association between object and name is unambiguous and children are more likely to learn the object’s name. Children also learn to name things other than solid objects, including nonsolid substances like applesauce. However, it is unknown how caregivers structure linguistic and exploratory experiences with nonsolids to support learning. In this exploratory study of caregivers and children we compare caregiver-child free-play with novel solid objects and novel nonsolid substances to identify the (...) linguistic and exploratory experiences associated with children’s word learning. We found systematic differences in interactions with novel objects, such that children performed more manual actions on solids than nonsolids and caregivers named solids more than nonsolids. Additionally, there was less synchrony between caregivers’ naming and children’s manual and visual exploration of nonsolids than solids. Consistent with prior work, we found that synchronous naming was associated with accurate recognition of solid object names. However, naming synchrony was not associated with recognition of nonsolid substance names or with generalization. Together these findings, though exploratory, suggest the coordination of caregiver-child play can shape what children remember about novel word-object associations for solid objects, but not nonsolid substances. (shrink)

The historical analysis of the complex and often contradictory views of Florence Nightingale regarding the rights of women is explored in this paper. Feminism and nursing are often viewed as contradictory and antithetical. The relationship between the two is examined through the link between Florence Nightingale and her contemporary, Barbara Leigh‐Smith Bodichon. Leigh‐Smith was founder and primary financier of The English Women's Journal that provided a public platform for the major feminist writings of the period. Its offices in Langham Place (...) formed the administrative centre of the Society for Promoting the Employment of Women. Bodichon and her colleagues were often referred to as the ‘Langham Place Group’. Unexplored prior to this study was the fact that Leigh‐Smith and Nightingale were first cousins. Utilizing techniques of internal and external criticism, primary and secondary sources were surveyed relating to Nightingale and Leigh‐Smith. The views of both women on the subjects of the rights of women, women's suffrage, the employment status of women, and the societal place of women are compared and contrasted. The legacy of both Leigh‐Smith and Nightingale to twentieth century feminism, the status of women, and the profession of nursing is then elaborated. The exploration of the views of both Nightingale and Leigh‐Smith is important to gain a clearer understanding of the existing relationship between nursing and feminism. In keeping with the aims of feminist inquiry, women's experiences, specifically those of Nightingale and Leigh‐Smith, are the major ‘objects’ of investigation. The concluding interpretation provides a synthesis that is emancipatory as well as knowledge generative. (shrink)

Recent judicial rulings and changes in federal and state legislation have given for-profit corporations a growing list of rights and constitutional protections, including the right to practice religion free from many types of federal or state restriction. In this paper, we highlight the implications of these developments using Rawls’ Theory of Justice to explore the consequences of for-profit corporate religious freedom for consumers and employees. We identify preliminary principles to spark a discussion as to how expanding religious freedom for businesses (...) and fair access to goods and services can coexist in the for-profit marketplace. (shrink)

Aeschylus' account of the sacrifice of Iphigeneia in theAgamemnonhas elicited an extraordinarily wide range of interpretations–a critical response which, in its veryproductivity, may signal a central aspect of the description itself. While more recent explications have been profitably informed by research in cult and ritual, there remains, I would like to suggest, an important literary possibility which merits consideration, particularly in a text where so much has been shaped from a close and profound engagement with the Homeric tradition. The description (...) of the sacrifice is forcefully carried by enjambement from one stanza into another by the sheer weight, as it were, of the force that crushingly silences, βίαι χαλινὦν τ᾿ άναύδωι μ⋯νει. In the midst of much that is dark and difficult to construe, the composition yields a sudden effusion of colour, a striking trail of saffron. The sense of concealment, of a figure enveloped or enshrouded, which has been suggested by the phrase πέπλοισι περιπετή, opens on to an image of unfolding, the falling spread of a robe caught in itsflow towards the ground, κρόκου βαφάς δ ⋯ς πέδονχέουσα. (shrink)

We review here the data indicating a role for epidermal growth factor receptor (EGF receptor) signalling in early mouse development. Embryonic development of the metazoan embryo generally begins with the formation of a cystic structure and epithelial layers that subsequently form anlagen of the definitive body parts and organs. For the mammalian embryo, this cystic structure is a blastocyst whose wall consists of trophectoderm, the first epithelium to develop during mammalian embryogenesis. The onset of expression and function of EGF receptors (...) is coincident with the onset of trophectoderm development. Modulating EGF receptor expression and function modulates trophectoderm differentiation, leading to the hypothesis that functional EGF receptors participate in the induction of trophectoderm development and perhaps of other embryonic epithelial derivatives such as nervous tissues. (shrink)