The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major.
We analyzed cardiac and liver T2* magnetic ...resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P<0.001) or serum ferritin (0.629; P<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P<0.001) or serum ferritin (0.518; P<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia.
Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.
ABSTRACT
We report on the discovery and validation of TOI 813 b (TIC 55525572 b), a transiting exoplanet identified by citizen scientists in data from NASA’s Transiting Exoplanet Survey Satellite ...(TESS) and the first planet discovered by the Planet Hunters TESS project. The host star is a bright (V = 10.3 mag) subgiant ($R_\star =1.94\, R_\odot$, $M_\star =1.32\, M_\odot$). It was observed almost continuously by TESS during its first year of operations, during which time four individual transit events were detected. The candidate passed all the standard light curve-based vetting checks, and ground-based follow-up spectroscopy and speckle imaging enabled us to place an upper limit of $2\, M_{\rm Jup}$ (99 per cent confidence) on the mass of the companion, and to statistically validate its planetary nature. Detailed modelling of the transits yields a period of $83.8911 _{ - 0.0031 } ^ { + 0.0027 }$ d, a planet radius of 6.71 ± 0.38 R⊕ and a semimajor axis of $0.423 _{ - 0.037 } ^ { + 0.031 }$ AU. The planet’s orbital period combined with the evolved nature of the host star places this object in a relatively underexplored region of parameter space. We estimate that TOI 813 b induces a reflex motion in its host star with a semi-amplitude of ∼6 m s−1, making this a promising system to measure the mass of a relatively long-period transiting planet.
For more than a decade, researchers have refined criteria for the diagnosis of dementia with Lewy bodies (DLB) and at the same time have recognized that cognitive impairment and dementia occur ...commonly in patients with Parkinson disease (PD). This article addresses the relationship between DLB, PD, and PD with dementia (PDD). The authors agreed to endorse "Lewy body disorders" as the umbrella term for PD, PDD, and DLB, to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of alpha-synuclein metabolism. We concluded that the differing temporal sequence of symptoms and clinical features of PDD and DLB justify distinguishing these disorders. However, a single Lewy body disorder model was deemed more useful for studying disease pathogenesis because abnormal neuronal alpha-synuclein inclusions are the defining pathologic process common to both PDD and DLB. There was consensus that improved understanding of the pathobiology of alpha-synuclein should be a major focus of efforts to develop new disease-modifying therapies for these disorders. The group agreed on four important priorities: 1) continued communication between experts who specialize in PDD or DLB; 2) initiation of prospective validation studies with autopsy confirmation of DLB and PDD; 3) development of practical biomarkers for alpha-synuclein pathologies; 4) accelerated efforts to find more effective treatments for these diseases.
Prion diseases are characterized by the cellular prion protein, PrP
, misfolding and aggregating into the infectious prion protein, PrP
, which leads to neurodegeneration and death. An early sign of ...disease is inflammation in the brain and the shift of resting glial cells to reactive astrocytes and activated microglia. Few therapeutics target this stage of disease. Mesenchymal stromal cells produce anti-inflammatory molecules when exposed to inflammatory signals and damaged tissue. Here, we show that adipose-derived mesenchymal stromal cells (AdMSCs) migrate toward prion-infected brain homogenate and produce the anti-inflammatory molecules transforming growth factor β (TGFβ) and tumor necrosis factor-stimulated gene 6 (TSG-6). In an in vitro model of prion exposure of both primary mixed glia and BV2 microglial cell line, co-culturing with AdMSCs led to a significant decrease in inflammatory cytokine mRNA and markers of reactive astrocytes and activated microglia. This protection against in vitro prion-associated inflammatory responses is independent of PrP
replication. These data support a role for AdMSCs as a beneficial therapeutic for decreasing the early onset of glial inflammation and reprogramming glial cells to a protective phenotype.
To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD).
EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All ...were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001.
During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio OR = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD.
Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.
Inorganic bromine plays a critical role in ozone and mercury depletions events (ODEs and MDEs) in the Arctic marine boundary layer. Direct observations of bromine species other than bromine oxide ...(BrO) during ODEs are very limited. Here we report the first direct measurements of hypobromous acid (HOBr) as well as observations of BrO and molecular bromine (Br2) by chemical ionization mass spectrometry at Barrow, Alaska in spring 2009 during the Ocean‐Atmospheric‐Sea Ice‐Snowpack (OASIS) campaign. Diurnal profiles of HOBr with maximum concentrations near local noon and no significant concentrations at night were observed. The measured average daytime HOBr mixing ratio was 10 pptv with a maximum value of 26 pptv. The observed HOBr was reasonably well correlated (R2 = 0.57) with predictions from a simple steady state photochemical model constrained to observed BrO and HO2 at wind speeds <6 m s−1. However, predicted HOBr levels were considerably higher than observations at higher wind speeds. This may be due to enhanced heterogeneous loss of HOBr on blowing snow coincident with higher wind speeds. BrO levels were also found to be higher at elevated wind speeds. Br2 was observed in significant mixing ratios (maximum = 46 pptv; average = 13 pptv) at night and was strongly anti‐correlated with ozone. The diurnal speciation of observed gas phase inorganic bromine species can be predicted by a time‐dependent box model that includes efficient heterogeneous recycling of HOBr, hydrogen bromide (HBr), and bromine nitrate (BrONO2) back to more reactive forms of bromine.
Key Points
First observations of HOBr are presented
Direct evidence for high winds activating bromine
HOBr can be reproduced with model including aerosol uptake
Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine ...have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect.
Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001).
In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.
Transverse microcrack growth and delamination are two key damage mechanisms in laminated composite materials, and while often treated separately in damage prediction studies, they are, in fact, ...highly coupled. Essentially, transverse cracks initiate around fibres, coalesce and grow until they extend to ply boundaries, at which point they initiate micro-delaminations. Under increasing load these micro-delaminations eventually coalesce to form macroscopic delaminations, which severely reduce material stiffness and lead to catastrophic failure of the composite structure. This paper presents an investigation into how altering transverse crack densities can influence the growth of delaminations. Novel in-situ SEM micromechanical testing and acoustic damage detection techniques were coupled and used to determine transverse crack initiation loads, transverse crack density, and local micro-delamination lengths for a number of cross-ply laminates. The laminates were loaded in a four-point bending mode to induce crack opening direct stresses on the tension side. To examine the effect of combined direct and shear stresses, the laminates were also loaded in a three-point bending mode, and suitable comparisons between both bending modes allowed for the influence of the shear stress to be isolated. The main variable under investigation is the thickness of the transverse ply block, and it is shown that increasing the number of transverse plies (i.e. thickness) can significantly increase the load carrying capacity of the laminate by reducing the transverse crack density. It was found that the lower transverse crack densities meant that the micro-delaminations which initiated at the ply boundary required significantly greater stress to fully coalesce as the distance between transverse cracks was greater. Once micro-delamination had initiated, its length was found to be linearly related to the load applied. For all layups investigated, the average micro-delamination length seen immediately prior to catastrophic failure was approximately 1.2times the thickness of the tensile 90° ply portion of the laminate.
► Al-doped zinc oxide (AZO) films are grown by atomic layer deposition (ALD) system. ► The transmittance of the film is 80–90% in visible spectrum. ► A reasonable transmittance up to 5000 nm in IR is ...observed for the first time. ► The conductivity of the films improved after post annealing in reducing ambient. ► These ALD grown AZO films are optimal for photovoltaic application.
We report transmittance and conductivity measurements of aluminum-doped zinc oxide films grown by atomic layer deposition. The results show that the films have 80–90% transmittance in the visible region and good transmittance in the infrared. To our knowledge, this is the first time that the transmittance of aluminum-doped zinc oxide is reported to extend beyond 2500–5000nm. Following annealing, an optimal sheet resistance of 25Ω/□ was obtained for a 575nm thick film with a carrier density of 2.4×1020cm−3 without compromising the transmittance in the visible regime.
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