The Composition of the Modernist Book: Ulysses, A Draft of XXX Cantos and The Making of Americans.

This is a study of the composition of three Modernist first editions: Ulysses (1922), The Making of Americans (1925) and A Draft of XXX Cantos (1930). The bibliographical and figurative commitments made to being in print by Ulysses, A Draft of XXX Cantos and The Making of Americans set a coherent program for reading Modernist texts in their perfected form: in print. The editorial reception of the Modernist book has proceeded, however, with reference to the editorial and bibliographical principles established by the New Bibliographers. In deferring to the authors and manuscripts of Modernist books as the highest source of textual authority, the vital significance of being in print to literary Modernism is obscured. The figure of the ideal Book concentrates the central aesthetic, intellectual and bibliographic problem posed the Modernist book: the making of literature. The rhyme with The Making of Americans is appropriate: this book intensifies and consolidates the propositions made about objective and autonomous composition made more hesitantly by Ulysses and A Draft of XXX Cantos. These three books display a gradual refusal to equate inscription and intention; their composition effaces all traces of a sovereign creative subjectivity. The vision of the book guides Modernist composition, and requires a critical distinction be drawn between manuscripts and printed letters. Modernism must be read in print. The vestigial nostalgia for Romantic modes of textual production and creation in Ulysses is repeated on the placards and proof-pages for the book. Printed drafts are revised and reformed by the pen of the author. The finality asserted by the printed letter is only reluctantly ceded on the publication of Ulysses. The composition of A Draft of XXX Cantos represents a further transition away from the script economy of Romanticism. The interplay between authorial typescripts, early publications and the first edition of A Draft of XXX Cantos assert an intermediate order of Modernist textuality which takes the printed page as its foundation. The Making of Americans relies on the absolute objectivity and anonymity of its composition for the effect of its narrative. Objectivity is the intellectual and aesthetic strategy which produces literature rather than the personality and memory of the author. The impersonality of the apparently automatically written manuscripts and scarcely revised typescripts for The Making of Americans severs the visible links between the writing author and her page. In their unwillingness to corroborate the modes of textual generation described by the New Bibliographers, these three books thematise their own composition as the exemplary Modernist and modern mode of textual generation. The Modernist book attenuates or denies a Romantic connection between the creative hand of the author and the surface image of the page: the mechanisms of print deliberately detach the author from the literary text. The distance of the author from the scene of textual reproduction is measured by the printed book. The composition of this analytical object is not a fallacy but an actuality, commemorated in the archive, enacted by the book. Modernism is the literature of the imprimatur rather than of authorial inscription and accordingly it is towards the first editions of Modernist texts that the attentions of editors and textual scholars must be directed

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

Subcortical brain alterations in major depressive disorder:findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset <= 21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth