250 research outputs found

    Magnetic Flux Braiding: Force-Free Equilibria and Current Sheets

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    We use a numerical nonlinear multigrid magnetic relaxation technique to investigate the generation of current sheets in three-dimensional magnetic flux braiding experiments. We are able to catalogue the relaxed nonlinear force-free equilibria resulting from the application of deformations to an initially undisturbed region of plasma containing a uniform, vertical magnetic field. The deformations are manifested by imposing motions on the bounding planes to which the magnetic field is anchored. Once imposed the new distribution of magnetic footpoints are then taken to be fixed, so that the rest of the plasma must then relax to a new equilibrium configuration. For the class of footpoint motions we have examined, we find that singular and nonsingular equilibria can be generated. By singular we mean that within the limits imposed by numerical resolution we find that there is no convergence to a well-defined equilibrium as the number of grid points in the numerical domain is increased. These singular equilibria contain current "sheets" of ever-increasing current intensity and decreasing width; they occur when the footpoint motions exceed a certain threshold, and must include both twist and shear to be effective. On the basis of these results we contend that flux braiding will indeed result in significant current generation. We discuss the implications of our results for coronal heating.Comment: 13 pages, 12 figure

    Presence of DNA from Chlamydia-like organisms in the nasal cavities of grey seal pups (Halichoerus grypus) and three different substrates present in a breeding colony

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    BackgroundChlamydia-like organisms (CLO) have been found to be present in many environmental niches, including human sewage and agricultural run-off, as well as in a number of aquatic species worldwide. Therefore, monitoring their presence in sentinel wildlife species may be useful in assessing the wider health of marine food webs in response to habitat loss, pollution and disease. We used nasal swabs from live (n?=?42) and dead (n?=?50) pre-weaned grey seal pups and samples of differing natal substrates (n?=?8) from an off-shore island devoid of livestock and permanent human habitation to determine if CLO DNA is present in these mammals and to identify possible sources.ResultsWe recovered CLO DNA from 32/92 (34.7%) nasal swabs from both live (n?=?17) and dead (n?=?15) seal pups that clustered most closely with currently recognised species belonging to three chlamydial families: Parachlamydiaceae (n?=?22), Rhabdochlamydiaceae (n?=?6), and Simkaniaceae (n?=?3). All DNA positive sediment samples (n?=?7) clustered with the Rhabdochlamydiaceae. No difference was found in rates of recovery of CLO DNA in live versus dead pups suggesting the organisms are commensal but their potential as opportunistic secondary pathogens could not be determined.ConclusionThis is the first report of CLO DNA being found in marine mammals. This identification warrants further investigation in other seal populations around the coast of the UK and in other areas of the world to determine if this finding is unique or more common than shown by this data. Further investigation would also be warranted to determine if they are present as purely commensal organisms or whether they could also be opportunistic pathogens in seals, as well as to investigate possible sources of origin, including whether they originated as a result of anthropogenic impacts, including human waste and agricultural run-off

    Management of Vascular Risk Factors in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

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    BackgroundThe Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors.Methods and ResultsManagement was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low‐density lipoprotein, cholesterol <100 mg/dL, systolic blood pressure <140 mm Hg, fasting blood glucose <126 mg/dL, and nonsmoking status. Optimal control was defined as achieving all 4 goals concurrently. Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow‐up visits for up to 48 months. In the analysis cohort of 2210, significant improvements in risk‐factor control were observed across risk factors for all follow‐up visits compared with baseline. At 48 months, achievement of the low‐density lipoprotein cholesterol goal improved from 59.1% to 73.6% (P<0.001), achievement of the systolic blood pressure goal improved from 51.6% to 65.1% (P<0.001), achievement of the glucose goal improved from 74.9% to 80.7% (P=0.0101), and nonsmoking improved from 74.4% to 80.9% (P<0.0001). The percentage with optimal risk‐factor control also improved significantly, from 16.7% to 36.2% (P<0.001), but nearly 2 of 3 study participants did not achieve optimal control during the study.ConclusionsSite‐based risk‐factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal. Intensive medical management should be considered for future trials of carotid revascularization.Clinical Trial RegistrationURL: ClinicalTrials.gov. Unique identifier: NCT00004732

    The place of values in the aims of school science education

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    Debates about the aims of school science education are perennial (e.g., Reiss & White, 2014; see also Kidman & Fensham, Chapter “ Intended, Achieved and Unachieved Values of Science Education” this volume), particularly in Western cultures. In this chapter we review some of these arguments about the aims of school science education, and look at what has changed in the last decade since one of us (Michael) considered a similar debate (see Reiss, 2007). We have situated this review of arguments in current global circumstances including rapid technological advances, a continuing demand for workers with STEM (Science, Technology, Engineering and Mathematics) qualifications and the increasing acknowledgement of the deeply worrying effects that humans have on the Earth’s ecology, and indeed its future. Part of our argument is that decisions about the aims of school science education are inevitably decisions about values in education in general and values in school science education more specifically. This means that for a country, a group of schools, an individual school or a classroom teacher to come to a view about the aims of science education in the classroom is to have made a judgement, implicitly or explicitly, about values

    Otx2 Gene Deletion in Adult Mouse Retina Induces Rapid RPE Dystrophy and Slow Photoreceptor Degeneration

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    International audienceBACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE

    The Waddlia Genome: A Window into Chlamydial Biology

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    Growing evidence suggests that a novel member of the Chlamydiales order, Waddlia chondrophila, is a potential agent of miscarriage in humans and abortion in ruminants. Due to the lack of genetic tools to manipulate chlamydia, genomic analysis is proving to be the most incisive tool in stimulating investigations into the biology of these obligate intracellular bacteria. 454/Roche and Solexa/Illumina technologies were thus used to sequence and assemble de novo the full genome of the first representative of the Waddliaceae family, W. chondrophila. The bacteria possesses a 2â€Č116â€Č312bp chromosome and a 15â€Č593 bp low-copy number plasmid that might integrate into the bacterial chromosome. The Waddlia genome displays numerous repeated sequences indicating different genome dynamics from classical chlamydia which almost completely lack repetitive elements. Moreover, W. chondrophila exhibits many virulence factors also present in classical chlamydia, including a functional type III secretion system, but also a large complement of specific factors for resistance to host or environmental stresses. Large families of outer membrane proteins were identified indicating that these highly immunogenic proteins are not Chlamydiaceae specific and might have been present in their last common ancestor. Enhanced metabolic capability for the synthesis of nucleotides, amino acids, lipids and other co-factors suggests that the common ancestor of the modern Chlamydiales may have been less dependent on their eukaryotic host. The fine-detailed analysis of biosynthetic pathways brings us closer to possibly developing a synthetic medium to grow W. chondrophila, a critical step in the development of genetic tools. As a whole, the availability of the W. chondrophila genome opens new possibilities in Chlamydiales research, providing new insights into the evolution of members of the order Chlamydiales and the biology of the Waddliaceae

    Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

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    Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health
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