274 research outputs found

    Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin- producing 2011 German outbreak Escherichia coli O104:H4

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    In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)—producing the biofilm-promoting second messenger c-di-GMP—that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS

    Dedicated breast computed-tomography in women with a personal history of breast cancer: A proof-of-concept study.

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    PURPOSE To compare the subjective image quality assessment using B-CT and digital mammography in women with personal history of breast cancer (PHBC). METHOD In this retrospective study 32 patients with PHBC were included. Each patient had undergone a B-CT examination and a previous mammogram in a time interval of less than 18 months between the two examinations. Two radiologists evaluated the two examinations independently with regard to the presence of lesions, BI-RADS classification, level of confidence for the overall exam interpretation, scar evaluation and image quality including image degradation due to clip artifacts. Level of confidence and image quality were assessed using a 5-point Likert scale. A p-value of less than 0.01 was considered statistically significant. RESULTS Thirty-seven operated and 27 non-operated breasts were included. Confidence for the overall interpretation with B-CT was equal or superior to mammography in 63 cases (98.4 %) for reader 1 and in 58 cases (90.6 %) for reader 2 (p <.001). Confidence for scar evaluation with B-CT was equal or superior to mammography in all cases for reader 1 and in 34 cases (91.9 %) for readers 2 (p <.001). One case with local recurrence in B-CT was identified by both readers and no false positive findings were reported. A moderate to high image degradation due to beam-hardening artifacts has been reported by both readers in 29.4 % of cases due to surgical clips in the B-CT volume. CONCLUSIONS B-CT in patients with PHBC provides high quality images that can be evaluated with confidence equal or superior to mammography

    Linking Canadian Administrative Data: Income Trajectories, Residential and School Mobility, and Grade 3 Academic Achievement.

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    Objective The objective is to examine the association between trajectories of childhood residential and school mobility and academic achievement (literacy, numeracy) in Grade 3 using linked whole-population administrative data in Manitoba, Canada. Secondarily, we assessed childhood residential/school mobility based on neighbourhood income levels (moving in/out of low- or mid-/high-income neighbourhoods). Approach This retrospective cohort study used linkable, de-identified administrative data (health, education, national census, provincial survey) from the provincial Population Research Data Repository housed at the Manitoba Centre for Health Policy (MCHP). Among kindergarteners from 2005 to 2014 (n = 83,894), those not having continuous residency in Manitoba, valid education assessments, and relevant family-level covariates were excluded. We followed this eligible cohort from kindergarten to Grade 3 based on various neighbourhood income trajectories of residential and school mobility. To assess Grade 3 literacy and numeracy scores based on trajectories, log-binomial regression models were conducted using SAS® version 9.4. Results The total cohort included 36,754 children; at the end of kindergarten, 14.2% resided in low-income neighbourhoods, and 84.8% lived in mid-/high-income neighbourhoods. Moving between two low-income neighborhoods between kindergarten to Grade 3 was associated with an increased risk of poor Grade 3 numeracy and literacy scores (numeracy aRR=1.39 [1.16,1.67]; literacy aRR=1.31 [1.08,1.59]). When moving between neighborhood income levels, the association was stronger for children moving into low-income neighbourhoods (e.g., mid-/high-income to low-income: numeracy aRR=1.41 [1.19,1.67]) than children moving into mid/high-income neighbourhoods (e.g., low-income to mid-/high-income: numeracy aRR=1.31 [1.08,1.59]). Changing schools between kindergarten and Grade 3 was also associated with poorer numeracy and literacy scores in Grade 3 (numeracy aRR=1.31 [1.22,1.40]; literacy aRR=1.34 [1.24,1.44]); however, the strength varied based on residential mobility patterns. Conclusion Moving homes/schools can differentially impact children’s educational attainment depending upon the income level of residing neighborhood(s). Stakeholders should recognize different levels of risks related to mobility and provide support accordingly to reduce the adverse impact. Support systems should be tailored to not only children but also families and neighbourhoods

    Drivers of abrupt Holocene shifts in West Antarctic ice stream direction from combined ice sheet modelling and geologic signatures

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    Determining the millennial-scale behaviour of marine-based sectors of the West Antarctic Ice Sheet (WAIS) is critical to improve predictions of the future contribution of Antarctica to sea level rise. Here high-resolution ice sheet modelling was combined with new terrestrial geological constraints (in situ14C and 10Be analysis) to reconstruct the evolution of two major ice streams entering the Weddell Sea over 20 000 years. The results demonstrate how marked differences in ice flux at the marine margin of the expanded Antarctic ice sheet led to a major reorganization of ice streams in the Weddell Sea during the last deglaciation, resulting in the eastward migration of the Institute Ice Stream, triggering a significant regional change in ice sheet mass balance during the early to mid Holocene. The findings highlight how spatial variability in ice flow can cause marked changes in the pattern, flux and flow direction of ice streams on millennial timescales in this marine ice sheet setting. Given that this sector of the WAIS is assumed to be sensitive to ocean-forced instability and may be influenced by predicted twenty-first century ocean warming, our ability to model and predict abrupt and extensive ice stream diversions is key to a realistic assessment of future ice sheet sensitivity

    Neighborhood disinvestment and severe maternal morbidity in the state of California

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    BACKGROUND Social determinants of health, including neighborhood context, may be a key driver of severe maternal morbidity and its related racial and ethnic inequities; however, investigations remain limited. OBJECTIVE This study aimed to examine the associations between neighborhood socioeconomic characteristics and severe maternal morbidity, as well as whether the associations between neighborhood socioeconomic characteristics and severe maternal morbidity were modified by race and ethnicity. STUDY DESIGN This study leveraged a California statewide data resource on all hospital births at ≥20 weeks of gestation (1997–2018). Severe maternal morbidity was defined as having at least 1 of 21 diagnoses and procedures (eg, blood transfusion or hysterectomy) as outlined by the Centers for Disease Control and Prevention. Neighborhoods were defined as residential census tracts (n=8022; an average of 1295 births per neighborhood), and the neighborhood deprivation index was a summary measure of 8 census indicators (eg, percentage of poverty, unemployment, and public assistance). Mixed-effects logistic regression models (individuals nested within neighborhoods) were used to compare odds of severe maternal morbidity across quartiles (quartile 1 [the least deprived] to quartile 4 [the most deprived]) of the neighborhood deprivation index before and after adjustments for maternal sociodemographic and pregnancy-related factors and comorbidities. Moreover, cross-product terms were created to determine whether associations were modified by race and ethnicity. RESULTS Of 10,384,976 births, the prevalence of severe maternal morbidity was 1.2% (N=120,487). In fully adjusted mixed-effects models, the odds of severe maternal morbidity increased with increasing neighborhood deprivation index (odds ratios: quartile 1, reference; quartile 4, 1.23 [95% confidence interval, 1.20–1.26]; quartile 3, 1.13 [95% confidence interval, 1.10–1.16]; quartile 2, 1.06 [95% confidence interval, 1.03–1.08]). The associations were modified by race and ethnicity such that associations (quartile 4 vs quartile 1) were the strongest among individuals in the “other” racial and ethnic category (1.39; 95% confidence interval, 1.03–1.86) and the weakest among Black individuals (1.07; 95% confidence interval, 0.98–1.16). CONCLUSION Study findings suggest that neighborhood deprivation contributes to an increased risk of severe maternal morbidity. Future research should examine which aspects of neighborhood environments matter most across racial and ethnic groups

    Argon, krypton, and xenon abundances in the solar wind measured in silicon from the genesis mission

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    Up to now solar wind (SW) abundances of Kr and Xe have been exclusively determined using SW irradiated regolith [1]. Hence, one of Genesis’s major objectives is to obtain the heavy noble gas composition of the present-day SW using artificial targets exposed to the SW for 2.5 years. SW abundances will allow to study fractionation processes upon SW formation, e.g., due to the first ionization potential (FIP-effect) [2]. This is of importance to deduce solar abundances of noble gases and other elements from SW data. Solar, i.e., photospheric, abundances of noble gases are indirectly determined due to the lack of suitable lines in the spectrum. Recently, solar abundance estimates for Ne and Ar were strongly reduced whereas Kr and Xe changed only slightly [3]. This led to a dramatic decrease of the solar Ar/Kr ratio by a factor of ~3 from the earlier value [4] of 2140. If true, this change would invalidate theories of heavy noble gas fractionation in the SW identified with regolith data [1, 5]. The Kr and Xe composition in present-day SW will enable us to reassess solar abundances and fractionation theories. Thus, we concentrate here on abundances of Ar, Kr and Xe in the bulk SW
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