538 research outputs found
Experimental performance of a conical pressure probe at Mach numbers of 3.0, 4.5, and 6.0
Wind tunnel investigation of performance of conical pressure probe at hypersonic speed
MULTIPLEX REAL TIME PCR and MELT CURVE ASSAY DEVELOPMENT FOR THE SIMULTANEOUS DETECTION AND IDENTIFICATION OF STREPTOCOCCUS PNEUMONIAE and STAPHYLOCOCCUS AUREUS
Staphylococcus aureus and Streptococcus pneumoniae are bacteria that commonly colonize healthy individuals without causing disease. Methicillin-resistant S. aureus (MRSA), a more virulent type of S. aureus, is carried by a small percentage of people. These two bacteria have an adversarial relationship both in vitro and in vivo, with S. pneumoniae being able to limit the growth of S. aureus. It has been hypothesized that the relationship between these bacteria may be altered in individuals immunized with the pneumococcal conjugate vaccine, raising concerns that vaccinated individuals may be more likely to carry MRSA. Assessing the carriage rate of these bacteria in both vaccinated and non-vaccinated individuals may provide important information to support or refute this hypothesis. To facilitate this study, we developed a multiplex Real Time Polymerase Chain Reaction (PCR) assay to simultaneously detect S. aureus and S. pneumoniae in the same sample
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Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.
PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome
Atenolol versus losartan in children and young adults with Marfan's syndrome
BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers.
METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period
A Burgessian critique of nominalistic tendencies in contemporary mathematics and its historiography
We analyze the developments in mathematical rigor from the viewpoint of a
Burgessian critique of nominalistic reconstructions. We apply such a critique
to the reconstruction of infinitesimal analysis accomplished through the
efforts of Cantor, Dedekind, and Weierstrass; to the reconstruction of Cauchy's
foundational work associated with the work of Boyer and Grabiner; and to
Bishop's constructivist reconstruction of classical analysis. We examine the
effects of a nominalist disposition on historiography, teaching, and research.Comment: 57 pages; 3 figures. Corrected misprint
Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome
A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneuploidy (DS + KS) associated with congenital heart defects have been published of which none had a double aortic arch. Our case report should draw attention to the possibility of a double aortic arch in patients with severe feeding and respiratory problems and a double aneuploidy
Quantification of radial arterial pulse characteristics change during exercise and recovery
It is physiologically important to understand the arterial pulse waveform characteristics change during exercise and recovery. However, there is a lack of a comprehensive investigation. This study aimed to provide scientific evidence on the arterial pulse characteristics change during exercise and recovery. Sixty-five healthy subjects were studied. The exercise loads were gradually increased from 0 to 125 W for female subjects and to 150 W for male subjects. Radial pulses were digitally recorded during exercise and 4-min recovery. Four parameters were extracted from the raw arterial pulse waveform, including the pulse amplitude, width, pulse peak and dicrotic notch time. Five parameters were extracted from the normalized radial pulse waveform, including the pulse peak and dicrotic notch position, pulse Area, Area1 and Area2 separated by notch point. With increasing loads during exercise, the raw pulse amplitude increased significantly with decreased pulse period, reduced peak and notch time. From the normalized pulses, the pulse Area, pulse Area1 and Area2 decreased, respectively, from 38 ± 4, 61 ± 5 and 23 ± 5 at rest to 34 ± 4, 52 ± 6 and 13 ± 5 at 150-W exercise load. During recovery, an opposite trend was observed. This study quantitatively demonstrated significant changes of radial pulse characteristics during different exercise loads and recovery phases
Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake
A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake.We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing.As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p =  0.001 and r2 = 0.40, p = 0.006, respectively).These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype
Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations
Background: Variants of several genes encoding transcription modulators, signal transduction, and structural proteins are known to cause Mendelian congenital heart disease (CHD). NKX2-5 and GATA4 were the first CHD-causing genes identified by linkage analysis in large affected families. Mutations of TBX5 cause Holt–Oram syndrome, which includes CHD as a clinical feature. All three genes have a well-established role in cardiac development.
Design: In order to investigate the possible role of multiple mutations in CHD, a combined mutation screening was performed in NKX2-5, GATA4, and TBX5 in the same patient cohort. Samples from a cohort of 331 CHD patients were analyzed by polymerase chain reaction, double high-performance liquid chromatography and sequencing in order to identify changes in the NKX2-5, GATA4, and TBX5 genes.
Results: Two cases of multiple heterozygosity of putative disease-causing mutations were identified. One patient was found with a novel L122P NKX2-5 mutation in combination with the private A1443D mutation of MYH6. A patient heterozygote for a D425N GATA4 mutation carries also a private mutation of the MYH6 gene (V700M).
Conclusions: In addition to reporting two novel mutations of NKX2-5 in CHD, we describe families where multiple individual mutations seem to have an additive effect over the pathogenesis of CHD. Our findings highlight the usefulness of multiple gene mutational analysis of large CHD cohorts
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