Romantic Sobriety

Winner, 2011 Jean-Pierre Barricelli Prize, International Conference on RomanticismThis book explores the relationship among Romanticism, deconstruction, and Marxism by examining tropes of sensation and sobriety in a set of exemplary texts from Romantic literature and contemporary literary theory.Orrin N. C. Wang explains how themes of sensation and sobriety, along with Marxist-related ideas of revolution and commodification, set the terms of narrative surrounding the history of Romanticism as a movement. The book is both polemical and critical, engaging in debates with modern thinkers such as Paul de Man, Jacques Derrida, Walter Benn Michaels, and Slavoj Žižek, as well as presenting fresh readings of late eighteenth- and early nineteenth-century writers, including Wordsworth, Kant, Shelley, Byron, Brontë, and Keats. Romantic Sobriety combines deeply complex, close readings with a broader reflection on Romanticism and its implications for literary study. It will interest scholars who study Romanticism from a number of perspectives, including those interested in bodily and social consumption, the roles of addiction and abstinence in literature, the connection between literary and visual culture, the intersection of critical theory and Romanticism, and the relationships among language, historical knowledge, and political practice

Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.11Nsciescopu

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Looking Backward, Looking Forward: MLA Members Speak

In 1997 I was asked to organize humanities outreach activities at the University of California, Irvine. The result was the formation of Humanities Out There (HOT). In our workshops, faculty members and graduate students supervise teams of undergraduates in order to take the methods and materials of the university into the larger community.I believe that programs like these will  become increasingly important in the next century, as economic, cultural, and educational divisions deepen in the wake of the demise of affirmative action and as the humanities fight to define their missions in a world driven by technology and its discontents. In this brave new world, what I call the new outreach may have a role to play in responding to social crises as they are visited on the life of the university. The new outreach will be driven by intellectual content, not public relations.It will take its orientation from the faculty rather than administrators. It will engage all the research disciplines rather than remain the purview of education departments. It will be integrated into the professional lives of its participants rather than rely on the spirit of volunteerism alone

Looking Backward, Looking Forward: MLA Members Speak

In 1997 I was asked to organize humanities outreach activities at the University of California, Irvine. The result was the formation of Humanities Out There (HOT). In our workshops, faculty members and graduate students supervise teams of undergraduates in order to take the methods and materials of the university into the larger community.I believe that programs like these will  become increasingly important in the next century, as economic, cultural, and educational divisions deepen in the wake of the demise of affirmative action and as the humanities fight to define their missions in a world driven by technology and its discontents. In this brave new world, what I call the new outreach may have a role to play in responding to social crises as they are visited on the life of the university. The new outreach will be driven by intellectual content, not public relations.It will take its orientation from the faculty rather than administrators. It will engage all the research disciplines rather than remain the purview of education departments. It will be integrated into the professional lives of its participants rather than rely on the spirit of volunteerism alone