166 research outputs found

    The radical Right, realism, and the politics of conservatism in postwar international thought

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    Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of the British International Studies Association. The rise of the radical Right over the last decade has created a situation that demands engagement with the intellectual origins, achievements, and changing worldviews of radical conservative forces. Yet, conservative thought seems to have no distinct place in the theoretical field that has structured debates within the discipline of IR since 1945. This article seeks to explain some of the reasons for this absence. In the first part, we argue that there was in fact a clear strand of radical conservative thought in the early years of the field's development and recover some of these forgotten positions. In the second part, we argue that the near disappearance of those ideas can be traced in part to a process of 'conceptual innovation' through which postwar realist thinkers sought to craft a 'conservative liberalism' that defined the emerging field's theoretical alternatives in ways that excluded radical right-wing positions. Recovering this history challenges some of IR's most enduring narratives about its development, identity, and commitments - particularly the continuing tendency to find its origins in a defining battle between realism and liberalism. It also draws attention to overlooked resources to reflect upon the challenge of the radical Right in contemporary world politics

    ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model

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    <p>Abstract</p> <p>Background</p> <p>We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE<sup>-/-</sup>) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.</p> <p>Methods</p> <p>Thickening of the aortic valve leaflets in apoE<sup>-/- </sup>mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.</p> <p>Results</p> <p>Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).</p> <p>Conclusion</p> <p>Moderate uremia causes thickening of the aortic valves in apoE<sup>-/- </sup>mice, which can be attenuated by ACE inhibition. The nephrectomized apoE<sup>-/- </sup>mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.</p

    Bicuspid stenotic aortic valves: clinical characteristics and morphological assessment using MRI and echocardiography

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    Background Bicuspid aortic valve (BAV) is one of the most common congenital heart defects with a population prevalence of 0.5% to 1.3%. Identifying patients with BAV is clinically relevant because BAV is associated with aortic stenosis, endocarditis and ascending aorta pathology. Methods and Results Patients with severe aortic stenosis necessitating aortic valve replacement surgery were included in this study. All dissected aortic valves Were stored in the biobank of the University Medical Centre Utrecht. Additionally to the morphological assessment of the aortic valve by the surgeon and pathologist, echocardiographic and magnetic resonance imaging (MRI) images were evaluated. A total of 80 patients were included of whom 32 (40%) were diagnosed with BAV by the surgeon (gold standard). Patients with BAV were significantly younger (55 vs 71 years) and were more frequently male. Notably, a significant difference was found between the surgeon and pathologist in determining valve morphology. MRI was performed in 33% of patients. MRI could assess valve morphology in 96% vs 73% with echocardiography. The sensitivity of MRI for BAV in a population of patients with severe aortic stenosis was higher than echocardiography (75% vs 55%), whereas specificity was better with the latter (91% vs 79%). Typically, the ascending aorta was larger in patients with BAV. Conclusion Among unselected patients with severe aortic valve stenosis, a high percentage of patients with BAV were found. Imaging and assessment of the aortic valve morphology when stenotic is challengin

    Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS) - registry Swabia

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    BACKGROUND: The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. METHODS/DESIGN: The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case–control study was implemented based on the registry that also included the collection of various biological materials. Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case–control study. All participants in the case–control study provided also a blood sample. The prospective part of the study is ongoing. DISCUSSION: The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms

    Impact of partial bivalent HPV vaccination on vaccine-type infection; a population-based analysis

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    Background: Data on the effectiveness of 1 dose of HPV vaccine are lacking, particularly in population-based settings. Data from a national HPV immunisation catch-up programme of 14-18 year old girls were used to assess the effectiveness of < 3 doses of the bivalent vaccine on vaccine-type and cross reactive-type HPV infection. Methods: Cervical samples from women attending for their first cervical smear which had been genotyped for HPV as part of a longitudinal HPV surveillance programme were linked to immunisation records to establish the number of vaccine doses (0,1,2,3) administered. Vaccine effectiveness (VE) adjusted for deprivation and age at first dose, was assessed for prevalent HPV 16/18 and HPV 31/33/45 infection.Results: VE for prevalent HPV 16/18 infection associated with 1, 2 and 3 doses was 48.2% (95% CI 16.8-68.9), 54.8% (95% CI 30.7-70.8) and 72.8% (95% CI 62.8-80.3). Equivalent VE for prevalent HPV 31/33/45 infection was -1.62% (95% CI -85.1 – 45.3), 48.3 % (95% CI 7.6 -71.8) and 55.2 % (95% CI 32.6-70.2).Conclusion: Consistent with recent aggregated trial data, we demonstrate the potential effectiveness of even one dose of HPV vaccine on vaccine type infection. Given that these women were immunised as part of a catch-up campaign, the VE observed in this study is likely to be an underestimate of what will occur in girls vaccinated at younger ages. Further population-based studies which look at the clinical efficacy of one dose schedules arewarranted

    Canadian Valuation of EQ-5D Health States: Preliminary Value Set and Considerations for Future Valuation Studies

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    Background The EQ-5D is a preference based instrument which provides a description of a respondent's health status, and an empirically derived value for that health state often from a representative sample of the general population. It is commonly used to derive Quality Adjusted Life Year calculations (QALY) in economic evaluations. However, values for health states have been found to differ between countries. The objective of this study was to develop a set of values for the EQ-5D health states for use in Canada. Methods Values for 48 different EQ-5D health states were elicited using the Time Trade Off (TTO) via a web survey in English. A random effect model was fitted to the data to estimate values for all 243 health states of the EQ-5D. Various model specifications were explored. Comparisons with EQ-5D values from the UK and US were made. Sensitivity analysis explored different transformations of values worse than dead, and exclusion criteria of subjects. Results The final model was estimated from the values of 1145 subjects with socio-demographics broadly representative of Canadian general population with the exception of Quebec. This yielded a good fit with observed TTO values, with an overall R2 of 0.403 and a mean absolute error of 0.044. Conclusion A preference-weight algorithm for Canadian studies that include the EQ-5D is developed. The primary limitations regarded the representativeness of the final sample, given the language used (English only), the method of recruitment, and the difficulty in the task. Insights into potential issues for conducting valuation studies in countries as large and diverse as Canada are gained

    Thyrotroph Embryonic Factor Regulates Light-Induced Transcription of Repair Genes in Zebrafish Embryonic Cells

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    Numerous responses are triggered by light in the cell. How the light signal is detected and transduced into a cellular response is still an enigma. Each zebrafish cell has the capacity to directly detect light, making this organism particularly suitable for the study of light dependent transcription. To gain insight into the light signalling mechanism we identified genes that are activated by light exposure at an early embryonic stage, when specialised light sensing organs have not yet formed. We screened over 14,900 genes using micro-array GeneChips, and identified 19 light-induced genes that function primarily in light signalling, stress response, and DNA repair. Here we reveal that PAR Response Elements are present in all promoters of the light-induced genes, and demonstrate a pivotal role for the PAR bZip transcription factor Thyrotroph embryonic factor (Tef) in regulating the majority of light-induced genes. We show that tefβ transcription is directly regulated by light while transcription of tefα is under circadian clock control at later stages of development. These data leads us to propose their involvement in light-induced UV tolerance in the zebrafish embryo

    Muscle and reflex changes with varying joint angle in hemiparetic stroke

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    <p>Abstract</p> <p>Background</p> <p>Despite intensive investigation, the origins of the neuromuscular abnormalities associated with spasticity are not well understood. In particular, the mechanical properties induced by stretch reflex activity have been especially difficult to study because of a lack of accurate tools separating reflex torque from torque generated by musculo-tendinous structures. The present study addresses this deficit by characterizing the contribution of neural and muscular components to the abnormally high stiffness of the spastic joint.</p> <p>Methods</p> <p>Using system identification techniques, we characterized the neuromuscular abnormalities associated with spasticity of ankle muscles in chronic hemiparetic stroke survivors. In particular, we systematically tracked changes in muscle mechanical properties and in stretch reflex activity during changes in ankle joint angle. Modulation of mechanical properties was assessed by applying perturbations at different initial angles, over the entire range of motion (ROM). Experiments were performed on both paretic and non-paretic sides of stroke survivors, and in healthy controls.</p> <p>Results</p> <p>Both reflex and intrinsic muscle stiffnesses were significantly greater in the spastic/paretic ankle than on the non-paretic side, and these changes were strongly position dependent. The major reflex contributions were observed over the central portion of the angular range, while the intrinsic contributions were most pronounced with the ankle in the dorsiflexed position.</p> <p>Conclusion</p> <p>In spastic ankle muscles, the abnormalities in intrinsic and reflex components of joint torque varied systematically with changing position over the full angular range of motion, indicating that clinical perceptions of increased tone may have quite different origins depending upon the angle where the tests are initiated.</p> <p>Furthermore, reflex stiffness was considerably larger in the non-paretic limb of stroke patients than in healthy control subjects, suggesting that the non-paretic limb may not be a suitable control for studying neuromuscular properties of the ankle joint.</p> <p>Our findings will help elucidate the origins of the neuromuscular abnormalities associated with stroke-induced spasticity.</p

    Surfactant secretion in LRRK2 knock-out rats : changes in lamellar body morphology and rate of exocytosis

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    Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revealed significantly enlarged lamellar bodies (LBs) in alveolar type II (ATII) epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca2+ release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca2+-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca2+ signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid) release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca2+ signaling and promotes LB exocytosis upon stimulation of ATII cells with ATP
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