96 research outputs found

    Mission Design for NASA's Inner Heliospheric Sentinels and ESA's Solar Orbiter Missions

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    This paper will document the mission design and mission analysis performed for NASA's Inner Heliospheric Sentinels (IHS) and ESA's Solar Orbiter (SolO) missions, which were conceived to be launched on separate expendable launch vehicles. This paper will also document recent efforts to analyze the possibility of launching the Inner Heliospheric Sentinels and Solar Orbiter missions using a single expendable launch vehicle, nominally an Atlas V 551

    Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry.

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    BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P CONCLUSIONS: The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen

    Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients

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    Background: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS).1,2 In particular, the total cerebral arterial blood flow (CABF), measured as a sum of all arterial flow in the neck, was associated with the cognitive performance of MS patients.3 Objective: To assess relationships between CABF and serum neurofilament light chain (sNfL), as neuronal damage biomarker with good prognostic value and treatment responsiveness.4 If the cerebrovascular changes are an independent pathophysiological factor in MS, a relationship should remain significant after controlling for common MS-based disease measures (i.e., T2 lesion volume and brain volume). Materials and methods: Total CABF was measured in 137 patients (86 clinically isolated syndrome (CIS)/relapsing-remitting (RR) and 51 progressive MS (PMS)) and 48 healthy controls (HCs) using Doppler ultrasound. sNfL was quantitated using a single molecule assay (Simoa). Three point zero T magnetic resonance imaging (MRI) examination allowed quantification of T2 lesion and whole-brain volume (WBV). Multiple linear regression models determined the sNfL associated with CABF after correction for demographic and MRI-derived variables. Results: After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained additional 2.6% of the sNfL variance (β=-0.167, p=0.044). (Table 1) CABF also remained significant in a step-wise regression model (β=0.18, p=0.034) upon the inclusion of T2 lesion burden and WBV effects. The explained sNfL variance improved from 17.4%, 22.7% with the presence of at least 2 CVD variable and 25.8% with both CVD and CABF predictors. Lastly, the disease-modifying therapy was not kept in the final model as an independent predictor of sNfL. Patients in the lowest CABF quartile (CABF≤761 mL/min) had significantly higher sNfL (34.6 pg/mL versus 23.9 pg/mL, adjusted-p=0.042) when compared to the highest quartile (CABF≥1130 mL/min). Conclusions: Lower CABF is associated with increased sNfL in MS patients, highlighting direct and independent relationship between cerebral hypoperfusion and axonal pathology. This relationship remained significant in the CIS/RRMS after adjusting for age, sex, and BMI effects

    Influenza Virus Infectivity Is Retained in Aerosols and Droplets Independent of Relative Humidity

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    Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was observed in both fine aerosols and stationary droplets. Our data suggest, for the first time, that influenza viruses remain highly stable and infectious in aerosols across a wide range of relative humidities. These results have significant implications for understanding the mechanisms of transmission of influenza and its seasonality

    Sensitivity and specificity for screening of chronic cerebrospinal venous insufficiency using a multimodal non-invasive imaging approach in patients with multiple sclerosis

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    The aim of this study was to investigate whether a combination of Doppler sonography (DS) and magnetic resonance venography (MRV) on 3T MRI increases specificity for detection of chronic cerebrospinal venous insufficiency (CCSVI) in 171 (113 relapsing-remitting, 47 secondary-progressive, 11 primary progressive) patients with multiple sclerosis (MS) and 79 age- and sexmatched healthy controls (HCs). One hundred ten (64.3%) MS patients and 30 (38%) HCs presented ≥2 venous hemodynamic CCSVI criteria (p<.0001). Both DS and MRV showed relatively high specificity but lower sensitivity for determining a CCSVI diagnosis in patients with MS vs HCs and between MS subgroups. In MS patients this diagnostic specificity increased to over 90% by combining internal jugular vein and vertebral vein abnormal DS and MRV findings, reflux in deep cerebral veins and MRV findings of >1 collateral veins. This study suggests that a multimodal non-invasive approach (DS and MRV) increases the specificity for a diagnosis of CCSVI in patients with MS

    Facilitating Pupil Thinking About Information Literacy

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    Whilst information literacy is frequently taught through the imposition on learners of an established framework, this paper suggests a different approach by taking a lead from James Herring’s ideas. Specifically, it provides guidance to school-based information professionals who would like to encourage their pupils to devise their own flexible, information literacy models which are unique to them. Drawing on existing material in information science and wider thought, it proposes areas for coverage and considers how information professionals may support the dynamic process of model construction. It is recommended that those who are intent on facilitating the creation of personal information literacy models help pupils to identify the roles they take on in their lives, to reflect on the information needs that result, to ascertain the information they require in particular situations, to explore their information-seeking activities, to consider means by which information can be captured and to give thought as to how the information they have accessed may be used. This framework is, however, by no means rigid and readers are, of course, free to make their own adjustments

    Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients

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    BACKGROUND: More than 85% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked MECP2 gene which encodes methyl-CpG-binding protein 2, a transcriptional repressor that binds methylated CpG sites. Because MECP2 is subject to X chromosome inactivation (XCI), girls with RTT express either the wild type or mutant MECP2 in each of their cells. To test the hypothesis that MECP2 mutations result in genome-wide transcriptional deregulation and identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we performed gene expression profiling of pure populations of untransformed T-lymphocytes that express either a mutant or a wild-type allele. METHODS: Single T lymphocytes from a patient with a c.473C>T (p.T158M) mutation and one with a c.1308-1309delTC mutation were subcloned and subjected to short term culture. Gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis. RESULTS: Expression profiling yielded 44 upregulated genes and 77 downregulated genes. We compared this gene list with expression profiles of independent microarray experiments in cells and tissues of RTT patients and mouse models with Mecp2 mutations. These comparisons identified a candidate MeCP2 target gene, SPOCK1, downregulated in two independent microarray experiments, but its expression was not altered by quantitative RT-PCR analysis on brain tissues from a RTT mouse model. CONCLUSION: Initial expression profiling from T-cell clones of RTT patients identified a list of potential MeCP2 target genes. Further detailed analysis and comparison to independent microarray experiments did not confirm significantly altered expression of most candidate genes. These results are consistent with other reported data
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