179 research outputs found

    The Scenario Planning Paradox

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    Austerity and Anti-Systemic Protest: Bringing Hardships Back In

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    This article explores the relationship between hardships and protest in the world-system. Despite the history of discussion of anti-systemic protest, there has been little work that differentiates world-systems contributions to social movement research from others who examine social movements. We contribute to a theory of anti-systemic protest by re-introducing hardships as a crucial element that defines inequalities in the world-system; one consistent source of those hardships are austerity policies imposed in response to debt negotiations. In addition to our path analyses which demonstrate the clear link of hardships and protest, our case studies provide further historical analysis on when globalization, political openings, and long-term hardships also help explain the occasion of protest.</p

    Shc depletion stimulates brown fat activity in vivo and in vitro.

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    Adipose tissue is an important metabolic organ that integrates a wide array of homeostatic processes and is crucial for whole-body insulin sensitivity and energy metabolism. Brown adipose tissue (BAT) is a key thermogenic tissue with a well-established role in energy expenditure. BAT dissipates energy and protects against both hypothermia and obesity. Thus, BAT stimulation therapy is a rational strategy for the looming pandemic of obesity, whose consequences and comorbidities have a huge impact on the aged. Shc-deficient mice (ShcKO) were previously shown to be lean, insulin sensitive, and resistant to high-fat diet and obesity. We investigated the contribution of BAT to this phenotype. Insulin-dependent BAT glucose uptake was higher in ShcKO mice. Primary ShcKO BAT cells exhibited increased mitochondrial respiration; increased expression of several mitochondrial and lipid-oxidative enzymes was observed in ShcKO BAT. Levels of brown fat-specific markers of differentiation, UCP1, PRDM16, ELOVL3, and Cox8b, were higher in ShcKO BAT. In vitro, Shc knockdown in BAT cell line increased insulin sensitivity and metabolic activity. In vivo, pharmacological stimulation of ShcKO BAT resulted in higher energy expenditure. Conversely, pharmacological inhibition of BAT abolished the improved metabolic parameters, that is the increased insulin sensitivity and glucose tolerance of ShcKO mice. Similarly, in vitro Shc knockdown in BAT cell lines increased their expression of UCP1 and metabolic activity. These data suggest increased BAT activity significantly contributes to the improved metabolic phenotype of ShcKO mice

    The influence of land cover data on farm-scale valuations of natural capital

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    The valuation of natural capital within individual farms could inform environmentally beneficial land use change and form the basis of agricultural subsidy schemes based on the provision of ecosystem services. Land cover extents can be used in a benefit transfer approach to produce monetary valuations of natural capital rapidly and at low cost. However, the methodology has not before been used within individual farms, and the impact of land cover data characteristics on the accuracy of valuations is uncertain. Here, we apply the approach to five UK farms of contrasting size, configuration and farming style, using three widely available land cover products. Results show that the land cover product used has a substantial impact on valuations, with differences of up to 58%, and the magnitude of this effect varies considerably according to the landscape structure of the farm. At most sites, valuation differences are driven by the extent of woodland recorded in the landscape, with higher resolution land cover products incorporating larger amounts of woodland through inclusion of smaller patches, leading to higher overall valuations. Integrating more accurate land cover data and accounting for the condition, configuration and location of natural capital has potential to improve the accuracy of valuations

    Gram-Scale Preparation of VAPOL Hydrogenphosphate: A Structurally Distinct Chiral Brønsted Acid

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    Abstract: A detailed gram-scale synthesis of VAPOL hydrogenphosphate, a structurally distinct chiral Brønsted acid, is presented. The reaction utilizes commercially available starting materials, proceeds with high yields and has been reproduced numerous times at scale

    The error of our ways: the experience of self-reported position in a location-based game

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    We present a study of people’s use of positional information as part of a collaborative location-based game. The game exploits self-reported positioning in which mobile players manually reveal their positions to remote players by manipulating electronic maps. Analysis of players’ movements, position reports and communications, drawing on video data, system logs and player feedback, highlights some of the ways in which humans generate, communicate and interpret position reports. It appears that remote participants are largely untroubled by the relatively high positional error associated with self reports. Our analysis suggests that this may because mobile players declare themselves to be in plausible locations such as at common landmarks, ahead of themselves on their current trajectory (stating their intent) or behind themselves (confirming previously visited locations). These observations raise new requirements for the future development of automated positioning systems and also suggest that selfreported positioning may be a useful fallback when automated systems are unavailable or too unreliable

    Effect of Once-Weekly Azithromycin vs Placebo in Children With HIV-Associated Chronic Lung Disease: The BREATHE Randomized Clinical Trial

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    Importance - HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation. Objective - To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. Design, Setting, and Participants - This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score Intervention - Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. Main Outcomes and Measures - All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. Results - A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, −0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, −0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events. Conclusions and Relevance - In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance

    Calcium channel blockade with nimodipine reverses MRI evidence of cerebral oedema following acute hypoxia

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    Acute cerebral hypoxia causes rapid calcium shifts leading to neuronal damage and death. Calcium channel antagonists improve outcomes in some clinical conditions, but mechanisms remain unclear. In 18 healthy participants we: (i) quantified with multiparametric MRI the effect of hypoxia on the thalamus, a region particularly sensitive to hypoxia, and on the whole brain in general; (ii) investigated how calcium channel antagonism with the drug nimodipine affects the brain response to hypoxia. Hypoxia resulted in a significant decrease in apparent diffusion coefficient (ADC), a measure particularly sensitive to cell swelling, in a widespread network of regions across the brain, and the thalamus in particular. In hypoxia, nimodipine significantly increased ADC in the same brain regions, normalizing ADC towards normoxia baseline. There was positive correlation between blood nimodipine levels and ADC change. In the thalamus, there was a significant decrease in the amplitude of low frequency fluctuations (ALFF) in resting state functional MRI and an apparent increase of grey matter volume in hypoxia, with the ALFF partially normalized towards normoxia baseline with nimodipine. This study provides further evidence that the brain response to acute hypoxia is mediated by calcium, and importantly that manipulation of intracellular calcium flux following hypoxia may reduce cerebral cytotoxic oedem

    Predictive analysis across spatial scales links zoonotic malaria to deforestation.

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    The complex transmission ecologies of vector-borne and zoonotic diseases pose challenges to their control, especially in changing landscapes. Human incidence of zoonotic malaria ( Plasmodium knowlesi) is associated with deforestation although mechanisms are unknown. Here, a novel application of a method for predicting disease occurrence that combines machine learning and statistics is used to identify the key spatial scales that define the relationship between zoonotic malaria cases and environmental change. Using data from satellite imagery, a case-control study, and a cross-sectional survey, predictive models of household-level occurrence of P. knowlesi were fitted with 16 variables summarized at 11 spatial scales simultaneously. The method identified a strong and well-defined peak of predictive influence of the proportion of cleared land within 1 km of households on P. knowlesi occurrence. Aspect (1 and 2 km), slope (0.5 km) and canopy regrowth (0.5 km) were important at small scales. By contrast, fragmentation of deforested areas influenced P. knowlesi occurrence probability most strongly at large scales (4 and 5 km). The identification of these spatial scales narrows the field of plausible mechanisms that connect land use change and P. knowlesi, allowing for the refinement of disease occurrence predictions and the design of spatially-targeted interventions
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