47 research outputs found
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One transition, many transitions? A corpus-based study of societal sustainability transition discourses in four civil society’s proposals
When the civil society makes ‘transition’ its label, it cannot be assumed that different civil society actors share compatible varieties of localist or radical transformationists discourses. This study has comparatively analyzed the discourses in four civil society sustainability transition proposals using a corpus-based methodology. We found that the proposals are similar as they identify the economy as an object and an entry point for transition, frame the economy as embedded in the socio–ecological system, ascribe agency to grassroots movements for transitions from the bottom–up. We also found crucial differences among the discourses regarding the role of the State, the degree of reform or radical innovation, the degree of imaginative character of the sustainability vision, the degree of opposition to capitalism. We suggest that insights on how the civil society employs notions of transition with respect to the themes of politics, emotions and place can help advance theorizations and practices of societal sustainability transitions led by the civil society
Quantitative modeling of the physiology of ascites in portal hypertension
Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy
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Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.
PURPOSE: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12. METHODS: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids. RESULTS: We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment. CONCLUSION: Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity
The effect of simulated obstructive apnea and hypopnea on aortic diameter and BP.
BACKGROUND: Preliminary evidence supports an association between obstructive sleep apnea (OSA) and thoracic aortic dilatation. The mechanisms through which OSA may promote thoracic aortic dilatation are incompletely understood. Therefore, we studied the acute effects of simulated apnea and hypopnea on aortic diameter and BP in humans. METHODS: The diameter of the aortic root was measured in 20 healthy volunteers by echocardiography, and peripheral BP was continuously recorded prior, during, and immediately after simulated obstructive hypopnea (inspiration through threshold load), simulated obstructive apnea (Müller maneuver), end-expiratory central apnea, and normal breathing in randomized order. RESULTS: Proximal aortic diameter increased significantly during inspiration through a threshold load (+6.48%; SE, 3.03; P = .007), but not during Müller maneuver (+3.86%; SE, 2.71; P = .336) or end-expiratory central apnea (+0.62%; SE, 2.94; P = .445). Maneuver-induced changes in mean BP were observed during inspiration through a threshold load (-10.5 mm Hg; SE, 2.2; P < .001), the Müller maneuver (-8.8 mm Hg; SE, 2.4; P < .001), and end-expiratory central apnea (-4.2 mm Hg; SE, 1.4; P = .052). There was a significant increase in mean BP on release of threshold load inspiration (+8.1 mm Hg; SE, 2.9 mm Hg; P = .002), Müller maneuver (+10.7 mm Hg; SE, 2.9; P < .001), and end-expiratory central apnea (+10.6 mm Hg; SE, 2.5; P < .001). CONCLUSIONS: Simulated obstructive hypopnea/apnea and central apnea induced considerable changes in BP, and obstructive hypopnea was associated with an increase in proximal aortic diameter. Further studies are needed to investigate effects of apnea and hypopnea on transmural aortic pressure and aortic diameter to define the role of OSA in the pathogenesis of aortic dilatation
Mannose-binding lectin protein and its association to clinical outcomes in COPD: a longitudinal study.
BACKGROUND: Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort. METHODS: We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter. Patients were dichotomized as frequent (>/= 2 AECOPD/year) or infrequent exacerbators. Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline. RESULTS: The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95% CI, 1.24-7.14, p = 0.01). The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]). Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum. However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test). CONCLUSIONS: In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival. The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989