Leading-effect vs. Risk-taking in Dynamic Tournaments: Evidence from a Real-life Randomized Experiment

Two 'order effects' may emerge in dynamic tournaments with information feedback. First, participants adjust effort across stages, which could advantage the leading participant who faces a larger 'effective prize' after an initial victory (leading-effect). Second, participants lagging behind may increase risk at the final stage as they have 'nothing to lose' (risk-taking). We use a randomized natural experiment in professional two-game soccer tournaments where the treatment (order of a stage-specific advantage) and team characteristics, e.g. ability, are independent. We develop an identification strategy to test for leading-effects controlling for risk-taking. We find no evidence of leading-effects and negligible risk-taking effects

Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: implications for targeting cancer stem cells

BACKGROUND LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS Nutrient stress was induced through glucose starvation. Glycosylation status was assessed using endoglycosidase or tunicamycin treatment. Flow cytometry and confocal microscopy were used to assess subcellular distribution of LGR5. RESULTS Glucose deprivation altered the glycosylation status of LGR5 resulting in reduced protein stability and cell surface expression. Furthermore, inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced localisation in the cis-Golgi network. CONCLUSIONS Nutrient stress within a tumour microenvironment has the capacity to alter LGR5 protein stability and membrane localisation through modulation of LGR5 glycosylation status. As LGR5 surface localisation is required for enhanced Wnt signalling, this is the first report to show a mechanism by which the microenvironment could affect LGR5 function

Dynamics of tournaments: the soccer case

A random walk-like model is considered to discuss statistical aspects of tournaments. The model is applied to soccer leagues with emphasis on the scores. This competitive system was computationally simulated and the results are compared with empirical data from the English, the German and the Spanish leagues and showed a good agreement with them. The present approach enabled us to characterize a diffusion where the scores are not normally distributed, having a short and asymmetric tail extending towards more positive values. We argue that this non-Gaussian behavior is related with the difference between the teams and with the asymmetry of the scores system. In addition, we compared two tournament systems: the all-play-all and the elimination tournaments.Comment: To appear in EPJ

Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms

Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht

Unsettling antibiosis: how might interdisciplinary researchers generate a feeling for the microbiome and to what effect?

Decades of active public health messaging about the dangers of pathogenic microbes has led to a Western society dominated by an antibiotic worldview; however recent scientific and social interest in the microbiome suggests an emerging counter-current of more probiotic sentiments. Such stirrings are supported by cultural curiosity around the ‘hygiene hypothesis’, or the idea it is possible to be ‘too clean’ and a certain amount of microbial exposure is essential for health. These trends resonate with the ways in which scientists too have adopted a more ‘ecological’ perspective on the microbiome. Advances in sequencing technologies and decreasing costs have allowed researchers to more rapidly explore the abundance and diversity of microbial life. This paper seeks to expand on such probiotic tendencies by proposing an interdisciplinary methodology researchers might use to generate more-than-antibiotic relations between lay participants and their domestic microbiome. The paper draws on findings from an ESRC-funded study, Good Germs, Bad Germs: Mapping microbial life in the kitchen (grant number ES/N006968/1), which sought to: (i) explore human-microbe relations in the domestic kitchen; and (ii) make scientific techniques for visualising the domestic microbiome available to non-expert publics through a form of ‘participatory metagenomics’. We examine how scientific knowledge and techniques are enroled into lay practices of making microbes sensible; how these intersect with, reinforce or disrupt previous feelings for microorganisms; and how new ways of relating with microbial others emerge. In reflecting on these findings we draw on work in animal geographies, environmental humanities and the social science of the microbiome. We examine how cultural, emotional and embodied responses to nonhuman others—their ability to affect ‘us’ humans—have implications for the ways in which public health authorities, researchers and ‘lay’ publics alike seek to engage with and govern nonhuman life. We argue that understanding and potentially generating different modes of relating to microbes—a feeling for the microbiome—offers opportunities for reconfiguring microbiopolitics and intervening into the ways in which publics respond to perceived microbial opportunities and threats

Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation

Developing a collaborative agenda for humanities and social scientific research on laboratory animal science and welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from enquiry in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they frame questions, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process underlines the value of interdisciplinary exchange for improving mutual understanding of different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Charisma and the Clinic

Here we argue that ‘charisma’, a concept widely taken up within geography and the environmental humanities, is of utility to the social studies of medicine. Charisma, we suggest, draws attention to the affective dimensions of medical work, the ways in which these affective relations are structured, and the manner in which they are intimately tied to particular material-discursive contexts. The paper differentiates this notion of charisma from Weber’s analyses of the ‘charismatic leader’ before detailing three forms of charisma - ecological (which relates to the affordances an entity has), corporeal (related to bodily interaction) and aesthetic (pertaining to an entity’s initial visual and emotional impact). Drawing on interview data we then show how this framework can be used to understand the manner in which psychologists and neuroscientists have come to see and act on autism. We conclude the article by suggesting that examining charisma within healthcare settings furthers the concept, in particular by drawing attention to the discursive features of ecologies and the ‘non-innocence’ of charisma

Extreme events and predictability of catastrophic failure in composite materials and in the Earth

Despite all attempts to isolate and predict extreme earthquakes, these nearly always occur without obvious warning in real time: fully deterministic earthquake prediction is very much a ‘black swan’. On the other hand engineering-scale samples of rocks and other composite materials often show clear precursors to dynamic failure under controlled conditions in the laboratory, and successful evacuations have occurred before several volcanic eruptions. This may be because extreme earthquakes are not statistically special, being an emergent property of the process of dynamic rupture. Nevertheless, probabilistic forecasting of event rate above a given size, based on the tendency of earthquakes to cluster in space and time, can have significant skill compared to say random failure, even in real-time mode. We address several questions in this debate, using examples from the Earth (earthquakes, volcanoes) and the laboratory, including the following. How can we identify ‘characteristic’ events, i.e. beyond the power law, in model selection (do dragon-kings exist)? How do we discriminate quantitatively between stationary and non-stationary hazard models (is a dragon likely to come soon)? Does the system size (the size of the dragon’s domain) matter? Are there localising signals of imminent catastrophic failure we may not be able to access (is the dragon effectively invisible on approach)? We focus on the effect of sampling effects and statistical uncertainty in the identification of extreme events and their predictability, and highlight the strong influence of scaling in space and time as an outstanding issue to be addressed by quantitative studies, experimentation and models