187 research outputs found
CONTEMPORARY SINGLE-STAGE TETRALOGY OF FALLOT REPAIR: EXCELLENT SURVIVAL BUT PHYSICAL OR NEURODEVELOPMENTAL COMPROMISE IN ONE FIFTH
Foetal echocardiographic assessment of borderline small left ventricles can predict the need for postnatal intervention
Abstract Background We sought to prospectively determine foetal echocardiographic factors associated with neonatal interventions in borderline hypoplastic left ventricles. Methods Foetuses were included who had a left ventricle that was 2-4 standard deviations below normal for length or diameter and had forward flow across the mitral and aortic valves. Factors associated with an intervention in the first month of life or no need for intervention were sought using univariate and multivariate logistic regression models. Results From 2005 to 2008, 47 foetuses meeting the criteria had an additional diagnosis (+foetal coarctation/+transverse arch hypoplasia): atrioventricular septal defect 7 (+2/+0), double outlet right ventricle 2 (+0/+0), Shone's complex 19 (+9/+4), and ventricular disproportion 19 (+13/+11; 4 both). There were seven pregnancies terminated, three foetal demises, and five had compassionate care. There were 32 livebirths that either had a biventricular repair (n = 20, n = 2 dead), univentricular palliation (n = 2, both alive), or no intervention (n = 9). Overall survival of livebirths to 6 months of age was 79%. Factors associated with early intervention on first foetal echocardiogram were: obstructed or retrograde arch flow (p = 0.08, odds ratio 3.3), coarctation (p = 0.05, odds ratio 11.4), and left ventricle outflow obstruction (p = 0.05, odds ratio 12.5). Neonatal factors included: Shone's diagnosis (p = 0.02, odds ratio 4.9), bicuspid aortic valve (p = 0.005, odds ratio 11.7), and larger tricuspid valve z-score (p = 0.05, odds ratio 3.6). A neonatal factor associated with no intervention was a larger mitral valve z-score (mean ā3.8 versus ā4.2 intervention group, p = 0.04, odds ratio 2.8). Discussion The need for early intervention in foetuses with borderline hypoplastic left ventricle can be predicted by foetal echocardiograph
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Three interacting freshwater plumes in the northern California Current System
The northern California Current System is impacted by two primary freshwater
sources: the Strait of Juan de Fuca and the Columbia River. The Columbia is frequently
bidirectional in summer, with branches both north and south of the river mouth
simultaneously. We describe the interaction of these two warm Columbia plumes with
each other and with the colder plume originating from the strait. The interactions occurred
when a period of strong downwelling-favorable winds and high Columbia River
discharge was followed by persistent and strong upwelling-favorable winds. The
northward plume that developed under the downwelling winds extended over 200 km
along the coast to the Strait of Juan de Fuca and into the strait. The plume subsequently
wrapped around Juan de Fuca Strait water in the counterclockwise seasonal eddy just
offshore of the strait. Inspection for similar wind and outflow conditions (>0.15 N mĀÆĀ²
and 10ā“ mĀ³ sĀÆĀ¹, respectively) suggest that these events might have occurred in roughly
half the years since 1994. Surface drifters deployed in the Columbia plume near its origin
tracked this plume water northward along the coast, then reversed direction at the onset
of upwelling-favorable winds, tracking plume water southward past the river mouth once
again. āāRecentāā (~1ā2 day old) and āāAgedāā (>14 day old) plume water folded around
the newly emerging southwest tending Columbia plume, forming a distinctive āāsockāā
shaped plume. This plume was a mixture of ~10% āāNewāā (<1 day old) water
and ~90% Recent and Aged water from prior north tending plumes
A Close Companion Search Around L Dwarfs Using Aperture Masking Interferometry and Palomar Laser Guide Star Adaptive Optics
We present a close companion search around 16 known early L dwarfs using aperture masking interferometry with Palomar laser guide star adaptive optics (LGS AO). The use of aperture masking allows the detection of close binaries, corresponding to projected physical separations of 0.6-10.0 AU for the targets of our survey. This survey achieved median contrast limits of ĪK ~ 2.3 for separations between 1.2Ī»/D-4Ī»/D and ĪK ~ 1.4 at 2/3Ī»/D. We present four candidate binaries detected with moderate-to-high confidence (90%-98%). Two have projected physical separations less than 1.5 AU. This may indicate that tight-separation binaries contribute more significantly to the binary fraction than currently assumed, consistent with spectroscopic and photometric overluminosity studies. Ten targets of this survey have previously been observed with the Hubble Space Telescope as part of companion searches. We use the increased resolution of aperture masking to search for close or dim companions that would be obscured by full aperture imaging, finding two candidate binaries. This survey is the first application of aperture masking with LGS AO at Palomar. Several new techniques for the analysis of aperture masking data in the low signal-to-noise regime are explored
Phase I, Single-Dose, Dose-Escalating Study of Inhaled Dry Powder Capreomycin: a New Approach to Therapy of Drug-Resistant Tuberculosis
ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults ( n = 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 Ī¼g/ml (MIC for Mycobacterium tuberculosis ) following the highest dose; the half-life ( t 1/2 ) was 4.8 Ā± 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis , suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen
Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin : a new approach to therapy of drug-resistant tuberculosis
Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults (n = 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 Ī¼g/ml (MIC for Mycobacterium tuberculosis) following the highest dose; the half-life (t1/2) was 4.8 Ā± 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis, suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen.Gates Foundation.http://aac.asm.orghb2013ay201
Mice lacking the neuropeptide Ī±-calcitonin gene-related peptide are protected against diet-induced obesity
Interplay of brain structure and function in neonatal congenital heart disease
Objective: To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity. Methods: We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring before surgery to assess functional brain maturation and network connectivity, structural magnetic resonance imaging (MRI) to determine the presence of brain injury and structural brain development, and diffusion tensor MRI to assess brain microstructural development. Results: Neonates with MRI brain injury and delayed structural and microstructural brain development demonstrated significantly stronger high-frequency (beta and gamma frequency band) connectivity. Furthermore, neonates with delayed microstructural brain development demonstrated significantly weaker low-frequency (delta, theta, alpha frequency band) connectivity. Neonates with brain injury also displayed delayed functional maturation of EEG background activity, characterized by greater background discontinuity. Interpretation: These data provide new evidence that early structural and microstructural developmental brain abnormalities can have immediate functional consequences that manifest as characteristic alterations of neuronal network connectivity. Such early perturbations of developing neuronal networks, if sustained, may be responsible for the persistent neurocognitive impairment prevalent in adolescent survivors of CHD. These foundational insights into the complex interplay between evolving brain structure and function may have relevance for a wide spectrum of neurological disorders manifesting early developmental brain injury
MRI reveals increased superior vena caval blood flow in human fetuses with congenital heart disease, abnormal placental pathology and neonatal brain white matter changes
Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD
Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. Ā© 2013 Rattray et al
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