This article argues that digital media are introducing a new grassroots-based mode of ‘citizen-initiated campaigning’ (CIC) that challenges the dominant professionalized model of campaign management ...by devolving power over core tasks to the grassroots. After defining the practice through reference to the 2008 campaign of Barack Obama and online parties literature, we devise a measure of CIC that is applied to UK parties in the 2010 election. Our findings show that CIC is emerging outside the U.S. and adoption is associated with major party status, although it may be of particular appeal to political actors facing a resource deficit. The conclusions focus on the implications of CIC for new forms of party membership, indirect voter mobilization and the contextual factors influencing this new model of campaigning.
While the study of e-participation has gained increasing attention within political science, our understanding of its underlying structure and relationship to offline participation is limited. This ...article addresses these gaps by focusing on three interrelated questions: (1) Is e-participation a multidimensional phenomenon (differentiation hypothesis)? (2) If submodes exist, do they mirror existing modes of participation (replication hypothesis)? (3) If offline forms are replicated online, do they mix together (integration hypothesis) or operate in separate spheres (independence hypothesis)? We test our hypotheses through confirmatory factor analysis of original survey data from the U.K. General Election of 2010. The results show that distinct submodes of e-participation, comparable to those occurring offline, can be identified. Support for integration and independence varies according to the type of participation undertaken. Finally our results suggest that the online environment may be fostering a new social-media-based type of expressive political behavior.
A core question addressed by parties and internet scholars is whether the medium is equalising or normalising levels of inter-party competition, Are minor parties better placed to compete for voters' ...attention online (equalisation), or do major parties continue to dominate (normalisation)? To date, most research has supported the latter scenario through ‘supply-side’ comparisons of website content in a single election. This article re-examines the debate using Australian surveys of election candidates conducted between 2001 and 2010. As well as providing the first longitudinal study of this question, we link the supply side with voter responses and compare how well the parties recruit support through their web campaigns. Our results confirm that major parties dominate in the adoption of personal websites, although minor parties are stronger users of social media. Both strategies are effective in gaining votes, suggesting that the web may be rebalancing if not equalising party competition.
Micro- and nano-scale particulate formulations are widely investigated towards improving the oral bioavailability of both biologics and drugs with low solubility and/or low intestinal permeability. ...Particulate formulations harnessing physiological intestinal transport pathways have recently yielded remarkably high oral bioavailabilities, illustrating the need for better understanding the specific pathways underpinning particle small intestinal absorption and the relative role of intestinal cells. Mechanistic knowledge has been hampered by the well acknowledged limitations of current in vitro, in vivo and ex vivo models relevant to the human intestinal physiology and the lack of standardization in studies reporting absorption data. Here we review the relevant literature and critically discusses absorption pathways with a focus on the role of specific intestinal epithelial and immune cells. We conclude that while Microfold (M) cells are a valid target for oral vaccines, enterocytes play a greater role in the systemic bioavailability of orally administrated particulate formulations, particularly within the sub-micron size range. We also comment on less-reported mechanisms such as paracellular permeability of particles, persorption due to cell damage and uptake by migratory immune cells.
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•High bioavailabilities have been achieved by particulate formulations harnessing physiological intestinal transport pathways.•This highlights the need for deeper understanding of the mechanisms underlying intestinal particles’ absorption.•Enterocytes are central to the intestinal absorption of submicron particles and their payloads.•Microphysiological intestinal models and organoids are powerful emerging tools to gain better insights.
Epithelial cells experience constant mechanical forces, including fluid shear stress (FSS) on their apical surface. These forces alter both structure and function. While precise recapitulation of the ...complex mechanobiology of organs remains challenging, better understanding of the effect of mechanical stimuli is necessary towards the development of biorelevant in vitro models. This is especially relevant to organs-on-chip models which allow for fine control of the culture environment. In this study, the effects of the FSS on Caco-2 cell monolayers were systematically determined using a microfluidic device based on Hele-Shaw geometry. This approach allowed for a physiologically relevant range of FSS (from ∼0 to 0.03 dyn/cm2) to be applied to the cells within a single device. Exposure to microfluidic FSS induced significant phenotypical and functional changes in Caco-2 cell monolayers as compared to cells grown in static conditions. The application of FSS significantly altered the production of mucus, expression of tight junctions, vacuolization, organization of cytoskeleton, formation of microvilli, mitochondrial activity and expression of cytochrome P450. In the context of the intestinal epithelium, this detailed understanding of the effects of the FSS will enable the realization of in vitro organs-on-chip models with well-defined and tailored characteristics to a specific purpose, including for drug and nanoparticle absorption studies. The Hele-Shaw approach used in this study could be readily applied to other cell types and adapted for a wide range of physiologically relevant FSS.
Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases ...neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies.
To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents.
A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch.
Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine) was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins) between the 3% dose of SB705498 and placebo for the cowhage challenge was -0.64, whilst the histamine challenge showed on average a -4.65 point change.
The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced itch.
ClinicalTrials.gov NCT01673529.
When the Nerds Go Marching In shows how digital technology has moved from the margins to the mainstream of campaign and election organization in contemporary democracies. Combining an extensive ...review of existing literature and comparative data sources with original survey evidence and web content analysis of digital campaign content across four nations—the United Kingdom, Australia, France, and the United States—the book maps the key shifts in the role and centrality of the internet in election campaigns over a twenty-year period. The chapters reveal how these countries have followed a four-phase model of digital campaign development which begins with experimentation, and is followed by a period of standardization and professionalization. Subsequent phases focus on increasingly strategic activities around the mobilization of activists and supporters, before switching to micro-targeted mobilizing of individual voters. The changes are mapped over time in each country from the perspective of both the campaigners (supply side), and that of voters (demand side), and the four nations are compared in terms of how far and fast they have moved through the developmental cycle. As well as providing the most comprehensive narrative charting the evolution of digital campaigning from its inception in the mid-1990s, the book also offers important insights into the national conditions that have been most conducive to its diffusion. Finally, based on the findings from the most recent phase of development, the book speculates on the future direction for political campaigns as they increasingly rely on digital tools and artificial intelligence for direction and decision-making during elections.
Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and ...learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy‐associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity.
Background
Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in ...Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis.
Methods
The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.
Results
The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions.
Conclusions
The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting‐specific, evidence‐based tool to help with the management of mucositis in patients who have cancer.
The Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology developed clinical practice guidelines for the management of mucositis, with the first edition published in 2004 and periodically updated. This summary presents the 2019/2020 guidelines update, which is based on a systematic review, and generates a tool that will help clinicians to select evidence‐based interventions.
The search for general properties in the structure of ecological networks is currently a very active area of research. Metaanalyses of published networks are a widely used technique. To have the best ...chance of discovering common properties though, networks should be constructed using a standardized approach. However, this is rarely the case, and pollination networks are constructed using two main methods: transects and timed observations. To investigate the potential for variation in network structure arising from different construction techniques we constructed plant—pollinator networks using two different methods at a single site, repeating our protocol over three field seasons. Transects and timed observation methods differ in the evenness of observation effort allocated among plant species in the observed community. We show that the uneven allocation of observation effort significantly affects the number of unique interactions in the network, and we reveal a strong trend in effects on web asymmetry and evenness of marginal abundance distributions. However, these effects do not appear to extend to the higher-order properties of connectance and nestedness.
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