536 research outputs found

    Designing citizen science tools for learning: lessons learnt from the iterative development of nQuire

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    This paper reports on a 4-year research and development case study about the design of citizen science tools for inquiry learning. It details the process of iterative pedagogy-led design and evaluation of the nQuire toolkit, a set of web-based and mobile tools scaffolding the creation of online citizen science investigations. The design involved an expert review of inquiry learning and citizen science, combined with user experience studies involving more than 200 users. These have informed a concept that we have termed ‘citizen inquiry’, which engages members of the public alongside scientists in setting up, running, managing or contributing to citizen science projects with a main aim of learning about the scientific method through doing science by interaction with others. A design-based research (DBR) methodology was adopted for the iterative design and evaluation of citizen science tools. DBR was focused on the refinement of a central concept, ‘citizen inquiry’, by exploring how it can be instantiated in educational technologies and interventions. The empirical evaluation and iteration of technologies involved three design experiments with end users, user interviews, and insights from pedagogy and user experience experts. Evidence from the iterative development of nQuire led to the production of a set of interaction design principles that aim to guide the development of online, learning-centred, citizen science projects. Eight design guidelines are proposed: users as producers of knowledge, topics before tools, mobile affordances, scaffolds to the process of scientific inquiry, learning by doing as key message, being part of a community as key message, every visit brings a reward, and value users and their time

    The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

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    The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

    The association between survey timing and patient-reported experiences with hospitals: results of a national postal survey

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    <p>Abstract</p> <p>Background</p> <p>Research on the effect of survey timing on patient-reported experiences and patient satisfaction with health services has produced contradictory results. The objective of this study was thus to assess the association between survey timing and patient-reported experiences with hospitals.</p> <p>Methods</p> <p>Secondary analyses of a national inpatient experience survey including 63 hospitals in the 5 health regions in Norway during the autumn of 2006. 10,912 (45%) patients answered a postal questionnaire after their discharge from hospital. Non-respondents were sent a reminder after 4 weeks. Multilevel linear regression analysis was used to assess the association between survey timing and patient-reported experiences, both bivariate analysis and multivariate analysis controlling for other predictors of patient experiences.</p> <p>Results</p> <p>Multivariate multilevel regression analysis revealed that survey time was significantly and negatively related to three of six patient-reported experience scales: doctor services (Beta = -0.424, <it>p</it>< 0.05), information about examinations (Beta = -0.566, <it>p </it>< 0.05) and organization (Beta = -0.528, <it>p </it>< 0.05). Patient age, self-perceived health and type of admission were significantly related to all patient-reported experience scales (better experiences with higher age, better health and routine admission), and all other predictors had at least one significant association with patient-reported experiences.</p> <p>Conclusions</p> <p>Survey time was significantly and negatively related to three of the six scales for patient-reported experiences with hospitals. Large differences in survey time across hospitals could be problematic for between-hospital comparisons, implying that survey time should be considered as a potential adjustment factor. More research is needed on this topic, including studies with other population groups, other data collection modes and a longer time span.</p

    Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

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    Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

    A population of luminous accreting black holes with hidden mergers

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    Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2x10^44 ergs per second) show a significant (P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the authors' version of the wor

    Interviewer BMI effects on under- and over-reporting of restrained eating: evidence from a national Dutch face-to-face survey and a postal follow-up

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    Contains fulltext : 102650pub.pdf (publisher's version ) (Open Access)Objectives To determine the effect of interviewer BMI on self-reported restrained eating in a face-to-face survey and to examine under- and over-reporting using the face-to face study and a postal follow-up. Methods A sample of 1,212 Dutch adults was assigned to 98 interviewers with different BMI who administered an eating questionnaire. To further evaluate misreporting a mail follow-up was conducted among 504 participants. Data were analyzed using two-level hierarchical models. Results Interviewer BMI had a positive effect on restrained eating. Normal weight and pre-obese interviewers obtained valid responses, underweight interviewers stimulated underreporting whereas obese interviewers triggered overreporting. Conclusion In face-to-face interviews self-reported dietary restraint is distorted by interviewer BMI. This result has implications for public health surveys, the more so given the expanding obesity epidemic.5 p

    A case study of possible future summer convective precipitation over the UK and Europe from a regional climate projection

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    Climate change caused by green house gas emissions is now following the trend of rapid warming consistent with a RCP8.5 forcing. Climate models are still unable to represent the mesoscale convective processes that occur at resolutions ∼O(3 km) and are not capable of resolving precipitation patterns in time and space with sufficient accuracy to represent convection. In this article, the UK Met Office precipitation observations are compared with the simulations for the period 1990–1995 followed by a simulation of a near‐future period 2031–2036 for a regional nested weather model. The convection‐permitting model, resolution ∼O(3 km), provides a good correspondence to the observational precipitation data and demonstrates the importance of explicit convection for future summer precipitation estimates. The UK summer precipitation is reduced slightly (∼10%) for 2031–2036 and there is no evidence of an increase in the peak maximum hourly precipitation magnitude. A similar pattern is observed over the whole European inner model domain. The results using the Kain–Fritsch convective parameterization scheme at a resolution ∼O(12 km) in the outer domain increase summer precipitation by ∼10% for the UK. The average precipitation rate per event increases, dry periods extend and wet periods shorten. As part of the change, 10‐m winds of <3 m s⁻¹ become more common – a scenario that would impact on power generation from wind turbines through calmer conditions and cause more frequent pollution episodes

    Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

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    Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus
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