68 research outputs found
Book Reviews
Afghanistan: Transition Under Threat. By Geoffrey Hayes and Mark Sedra, editors. Enemies of Intelligence: Knowledge & Power in American National Security. By Richard K. Betts
Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate
Background Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors. Objective To assess structural damage progression through 2 years. Methods Intention-to-treat patients with one post-baseline radiograph (rituximab n = 281; placebo n = 187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received >= 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104. Results At week 104, significantly lower changes in TSS (1.14 vs 2.81; p < 0.0001), erosion score (0.72 vs 1.80; p < 0.0001) and joint space narrowing scores (0.42 vs 1.00; p < 0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years. Conclusions Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitor
Modulation of nucleosome dynamics in Huntington's disease
Transcriptional dysregulation and aberrant chromatin remodeling are central features in the pathology of Huntington's disease (HD). In order to more fully characterize these pathogenic events, an assessment of histone profiles and associated gene changes were performed in transgenic N171-82Q (82Q) and R6/2 HD mice. Analyses revealed significant chromatin modification, resulting in reduced histone acetylation with concomitant increased histone methylation, consistent with findings observed in HD patients. While there are no known interventions that ameliorate or arrest HD progression, DNA/RNA-binding anthracyclines may provide significant therapeutic potential by correcting pathological nucleosome changes and realigning transcription. Two such anthracyclines, chromomycin and mithramycin, improved altered nucleosome homeostasis in HD mice, normalizing the chromatin pattern. There was a significant shift in the balance between methylation and acetylation in treated HD mice to that found in wild-type mice, resulting in greater acetylation of histone H3 at lysine 9 and promoting gene transcription. Gene expression profiling in anthracycline-treated HD mice showed molecular changes that correlate with disease correction, such that a subset of downregulated genes were upregulated with anthracycline treatment. Improved nucleosomal dynamics were concurrent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice. These data show the ability of anthracycline compounds to rebalance epigenetic histone modification and, as such, may provide the rationale for the design of human clinical trials in HD patient
Iconic dishes, culture and identity: the Christmas pudding and its hundred years’ journey in the USA, Australia, New Zealand and India
Asserting that recipes are textual evidences reflecting the society that produced them, this article explores the evolution of the recipes of the iconic Christmas pudding in the United States, Australia, New Zealand and India between the mid-nineteenth and the mid-twentieth centuries. Combining a micro-analysis of the recipes and the cookbook that provided them with contemporary testimonies, the article observes the dynamics revealed by the preparation and consumption of the pudding in these different societies. The findings demonstrate the relevance of national iconic dishes to the study of notions of home, migration and colonization, as well as the development of a new society and identity. They reveal how the preservation, transformation and even rejection of a traditional dish can be representative of the complex and sometimes conflicting relationships between colonists, migrants or new citizens and the places they live in
Book Reviews
Afghanistan: Transition Under Threat. By Geoffrey Hayes and Mark Sedra, editors.
Enemies of Intelligence: Knowledge & Power in American National Security. By Richard K. Betts
Book Reviews - "The Rising: Ireland: Easter 1916," Fearghal McGarry and "Guerrilla Warfare in the Irish War of Independence, 1919-1921," Joseph McKenna
Avenue of Spies: A True Story of Terror, Espionage, and One American Family’s Heroic Resistance in Nazi-Occupied Paris. By Alex Kershaw. New York: Crown Publishers, 2015.
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