6,927 research outputs found

    Paying the price: why parties that turn their back on civil society face electoral upheaval

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    Political parties are increasingly confronted with high levels of electoral volatility. Nick Martin, Sarah de Lange and Wouter van der Brug write, however, that even in times of increased volatility, connections between party elites and organised civil society matter electorally. Drawing on a new study, they illustrate how these ties can help to stabilise the electorates of parties on both the left and right

    Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxaneâ„¢) for peritoneal carcinomatosis : a phase I first-in-human study

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    Background: Nanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, Abraxane (TM)) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (Taxol (TM)). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer. Methods: Eligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m(2) using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses. Discussion: ABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy

    Striatal neurons expressing D1 and D2 receptors are morphologically distinct and differently affected by dopamine denervation in mice

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    The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease

    Empirical Challenges in Organizational Aesthetics Research: Towards a Sensual Methodology

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    Despite growing scholarly interest in aesthetic dimensions of organizational life, there is a lack of literature expressly engaging with the methodological mechanics of 'doing aesthetics research'. This article addresses that gap. It begins with an overview of the conceptual idiosyncrasies of 'aesthetics' as a facet of human existence and maps out the challenges these pose for empirical research methodology. A review of methodological approaches adopted to date in empirical studies of organizational aesthetics is then presented. The remainder of the article draws on the author's experiences and suggests methods and techniques to address both conceptual and practical challenges encountered during the execution of an organizational aesthetics research project. The article calls for a firmer focus on the aesthetic experiences of organizational members in addition to those of researchers and concludes with some suggestions as to the future of such 'sensual methodologies' </jats:p

    NO2 and PM2.5 Exposures and Lung Function in Swiss Adults: Estimated Effects of Short-Term Exposures and Long-Term Exposures with and without Adjustment for Short-Term Deviations

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    Background: The impact of nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter of less than or equal to 2.5. microns (PM2.5) exposures on lung function has been investigated mainly in children and less in adults. Furthermore, it is unclear whether short-term deviations of air pollutant concentration need to be considered in long-term exposure models. Objectives: The aims of this study were to investigate the association between short-term air pollution exposure and lung function and to assess whether short-term deviations of air pollutant concentration should be integrated into long-term exposure models. Methods: Short-term (daily averages 0–7 d prior) and long-term (1- and 4-y means) NO2 and PM2.5 concentrations were modeled using satellite, land use, and meteorological data calibrated on ground measurements. Forced expiratory volume within the first second (FEV1) of forced exhalation and forced vital capacity (FVC) were measured during a LuftiBus assessment (2003–2012) and linked to exposure information from the Swiss National Cohort for 36,085 adults (ages 18–95 y). We used multiple linear regression to estimate adjusted associations, and additionally adjusted models of long-term exposures for short-term deviations in air pollutant concentrations. Results: A 10μg/m3 increase in NO2 and PM2.5 on the day of the pulmonary function test was associated with lower FEV1 and FVC (NO2: FEV1 −8.0 ml [95% confidence interval: −13.4, −2.7], FVC −16.7 ml [−23.4, −10.0]; PM2.5: FEV1 −15.3 ml [−21.9, −8.7], FVC −18.5 ml [−26.5, −10.5]). A 10μg/m3 increase in 1-y mean NO2 was also associated with lower FEV1 (−7.7 ml; −15.9, 0.5) and FVC (−21.6 ml; −31.9, −11.4), as was a 10μg/m3 increase in 1-y mean PM2.5 (FEV1: −42.2 ml; −56.9, −27.5; FVC: −82.0 ml; −100.1, −63.9). These associations were robust to adjustment for short-term deviations in the concentration of each air pollutant. Conclusions: Short- and long-term air pollution exposures were negatively associated with lung function, in particular long-term PM2.5 exposure with FVC. Our findings contribute substantially to the evidence of adverse associations between air pollution and lung function in adults. https://doi.org/10.1289/EHP752

    Aptamer-based extraction of ergot alkaloids from ergot contaminated rye feed

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    Ergot alkaloids are mycotoxins which can be found in food based on cereal-crops, due to a contamination of plants by fungi of the genus Claviceps. The ingestion of ergot contaminated cereal crops can lead to a severe poisoning known as ergotism. For food and feed safety purposes, the extraction of ergot alkaloids from ergot contaminated flour was investigated. For the specific recognition of ergot alkaloids, DNA aptamer ligands specially selected for ergot alkaloids were grafted onto silica gel in order to construct a specific solid phase extraction system. The aptamer-functionalized silica gels were used to extract ergot alkaloids from a contaminated rye feed sample. The presence of ergot alkaloids eluted from the aptamer-functionalized silica gels was analyzed using LC-QTOF-MS. By using this simple system, it was possible to specifically extract ergosine, ergokryptine and ergocornine from an ergot contaminated rye feed sample. This aptamer-based extraction tool shows the applicability of aptamers for the specific extraction of toxins or natural compounds from turbid matrices in a one-step procedure
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