Georgian plasterwork in Britain: historiography, interpretation, restoration. A case study of Fairfax House, York.

Fairfax House, a mid-eighteenth-century house in York, was restored in the 1980s and is now a museum. The house is examined in this thesis as the focus of a complex process of material change and interpretative development over time. In particular, the thesis explores the significance of the interior decorative plasterwork at the house in its social, cultural, material and aesthetic dimensions. The plasterwork and the house that contains it are material objects that have been subject to change over time, not only in substance but in the way they have been perceived and the meanings they have accrued. The full exploration of this dynamic process requires that they are analysed not only in the context of the eighteenth century, when both were created, but also the twentieth century, when the house was restored. The plasterwork played a central role in that restoration because of the significance it had developed among York’s ‘neo-Georgians’, the influential group of conservation-minded individuals centred on York Civic Trust, who sought to bring the perceived qualities of Georgian civilisation to bear upon aesthetics and civic culture of modern York. The restoration of Fairfax House, which involved not only the reshaping of the plasterwork’s material substance but also of its meaning and interpretation, was central to that process. Plasterwork itself is a marginalised field of study in architectural history and the thesis begins with a consideration of the historiography of plasterwork and the issues that arise from its study. The thesis then explores the place of Fairfax House, and specifically its plasterwork, in the culture and imagination of twentieth-century York, analysing the development of interest in the ‘Georgian’ and in the conservation of eighteenth-century buildings in York, the restoration of 1982-4 itself, and ends with a case study involving a close reading of the plasterwork on the Great Staircase in the house and an analysis of the way it has been interpreted and presented

"Like Crossing Hell on a Rotten Rail--Dangerous": The Civil War Diary of Hoosier Samuel P. Herrington

Diary of Sergeant Samuel P. Herrington, Civil War soldier from Indiana

Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease

Background: Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. Methods and results: Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: “26–32 (All)” [lowest level], “20–25”, “15–19”, “1–14”, and “No Teeth” [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14–1.29), interleukin 6 1.14 (1.10–1.18), lipoprotein-associated phospholipase A2 activity 1.05 (1.03–1.06), growth differentiation factor 15 1.11 (1.08–1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11–1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98–1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact. Conclusions: A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal alzheimer\u27s disease: A preliminary study

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer\u27s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. Results: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401). Conclusions: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations

Images of sexual stereotypes in rap videos and the health of African American female adolescents

ABSTRACT Objective: This study sought to determine whether perceiving portrayals of sexual stereotypes in rap music videos was associated with adverse health outcomes among African American adolescent females. Methods: African American female adolescents (n ‫؍‬ 522) were recruited from community venues. Adolescents completed a survey consisting of questions on sociodemographic characteristics, rap music video viewing habits, and a scale that assessed the primary predictor variable, portrayal of sexual stereotypes in rap music videos. Adolescents also completed an interview that assessed the health outcomes and provided urine for a marijuana screen. Results: In logistic regression analyses, adolescents who perceived more portrayals of sexual stereotypes in rap music videos were more likely to engage in binge drinking (OR 3.8, 95% CI 1.32-11.04, p ‫؍‬ 0.01), test positive for marijuana (OR 3.4, 95% CI 1.19-9.85, p ‫؍‬ 0.02), have multiple sexual partners (OR 1.9, 95% CI 1.01-3.71, p ‫؍‬ 0.04), and have a negative body image (OR 1.5, 95% CI 1.02-2.26, p ϭ 0.04). This is one of the first studies quantitatively examining the relationship between cultural images of sexual stereotypes in rap music videos and a spectrum of adverse health outcomes in African American female adolescents. Conclusions: Greater attention to this social issue may improve the health of all adolescent females. 115

Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients

<p>Abstract</p> <p>Background</p> <p>Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, <it>ITGB1BP2</it>, in the modification of the clinical phenotype of human cardiomyopathies, we screened the <it>ITGB1BP2 </it>gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy</p> <p>Methods</p> <p>We analyzed <it>ITGB1BP2 </it>by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.</p> <p>Results</p> <p>Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.</p> <p>Conclusions</p> <p>The three variations of the <it>ITGB1BP2 </it>gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.</p> <p>Our analysis revealed an extremely low number of variations in the <it>ITGB1BP2 </it>gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.</p

Distillation of continuous-variable entanglement with optical means

We present an event-ready procedure that is capable of distilling Gaussian two-mode entangled states from a supply of weakly entangled states that have become mixed in a decoherence process. This procedure relies on passive optical elements and photon detectors distinguishing the presence and the absence of photons, but does not make use of photon counters. We identify fixed points of the iteration map, and discuss in detail its convergence properties. Necessary and sufficient criteria for the convergence to two-mode Gaussian states are presented. On the basis of various examples we discuss the performance of the procedure as far as the increase of the degree of entanglement and two-mode squeezing is concerned. Finally, we consider imperfect operations and outline the robustness of the scheme under non-unit detection efficiencies of the detectors. This analysis implies that the proposed protocol can be implemented with currently available technology and detector efficiencies.Comment: 14 pages, 12 figure

Discovery of a single male Aedes aegypti (L.) in Merseyside, England

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