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Paediatric heart transplantation: life-saving but not yet a cure
- Robert Boucek, Richard Chinnock, Janet Scheel, Shriprasad R. Deshpande, Simon Urschel, James Kirklin
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- Journal:
- Cardiology in the Young / Volume 34 / Issue 2 / February 2024
- Published online by Cambridge University Press:
- 23 January 2024, pp. 233-237
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In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic “advantages,” including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients’ post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding “incentives” such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.
Quantitative cardiac magnetic resonance T2 imaging offers ability to non-invasively predict acute allograft rejection in children
- Neeta Sethi, Ashish Doshi, Tina Doshi, Russell Cross, Ileen Cronin, Elena Amin, Joshua Kanter, Janet Scheel, Sairah Khan, Adrienne Campbell-Washburn, Laura Olivieri
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- Journal:
- Cardiology in the Young / Volume 30 / Issue 6 / June 2020
- Published online by Cambridge University Press:
- 27 May 2020, pp. 852-859
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Background:
Monitoring for acute allograft rejection improves outcomes after cardiac transplantation. Endomyocardial biopsy is the gold standard test defining rejection, but carries risk and has limitations. Cardiac magnetic resonance T2 mapping may be able to predict rejection in adults, but has not been studied in children. Our aim was to evaluate T2 mapping in identifying paediatric cardiac transplant patients with acute rejection.
Methods:Eleven paediatric transplant patients presenting 18 times were prospectively enrolled for non-contrast cardiac magnetic resonance at 1.5 T followed by endomyocardial biopsy. Imaging included volumetry, flow, and T2 mapping. Regions of interest were manually selected on the T2 maps using the middle-third technique in the left ventricular septal and lateral wall in a short-axis and four-chamber slice. Mean and maximum T2 values were compared with Student’s t-tests analysis.
Results:Five cases of acute rejection were identified in three patients, including two cases of grade 2R on biopsy and three cases of negative biopsy treated for clinical symptoms attributed to rejection (new arrhythmia, decreased exercise capacity). A monotonic trend between increasing T2 values and higher biopsy grades was observed: grade 0R T2 53.4 ± 3 ms, grade 1R T2 54.5 ms ± 3 ms, grade 2R T2 61.3 ± 1 ms. The five rejection cases had significantly higher mean T2 values compared to cases without rejection (58.3 ± 4 ms versus 53 ± 2 ms, p = 0.001).
Conclusions:Cardiac magnetic resonance with quantitative T2 mapping may offer a non-invasive method for screening paediatric cardiac transplant patients for acute allograft rejection. More data are needed to understand the relationship between T2 and rejection in children.
Global and local statistics in turbulent convection at low Prandtl numbers
- Janet D. Scheel, Jörg Schumacher
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- Journal:
- Journal of Fluid Mechanics / Volume 802 / 10 September 2016
- Published online by Cambridge University Press:
- 01 August 2016, pp. 147-173
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Statistical properties of turbulent Rayleigh–Bénard convection at low Prandtl numbers $Pr$, which are typical for liquid metals such as mercury or gallium ($Pr\simeq 0.021$) or liquid sodium ($Pr\simeq 0.005$), are investigated in high-resolution three-dimensional spectral element simulations in a closed cylindrical cell with an aspect ratio of one and are compared to previous turbulent convection simulations in air for $Pr=0.7$. We compare the scaling of global momentum and heat transfer. The scaling exponent $\unicode[STIX]{x1D6FD}$ of the power law $Nu=\unicode[STIX]{x1D6FC}Ra^{\unicode[STIX]{x1D6FD}}$ is $\unicode[STIX]{x1D6FD}=0.265\pm 0.01$ for $Pr=0.005$ and $\unicode[STIX]{x1D6FD}=0.26\pm 0.01$ for $Pr=0.021$, which are smaller than that for convection in air ($Pr=0.7$, $\unicode[STIX]{x1D6FD}=0.29\pm 0.01$). These exponents are in agreement with experiments. Mean profiles of the root-mean-square velocity as well as the thermal and kinetic energy dissipation rates have growing amplitudes with decreasing Prandtl number, which underlies a more vigorous bulk turbulence in the low-$Pr$ regime. The skin-friction coefficient displays a Reynolds number dependence that is close to that of an isothermal, intermittently turbulent velocity boundary layer. The thermal boundary layer thicknesses are larger as $Pr$ decreases and conversely the velocity boundary layer thicknesses become smaller. We investigate the scaling exponents and find a slight decrease in exponent magnitude for the thermal boundary layer thickness as $Pr$ decreases, but find the opposite case for the velocity boundary layer thickness scaling. A growing area fraction of turbulent patches close to the heating and cooling plates can be detected by exceeding a locally defined shear Reynolds number threshold. This area fraction is larger for lower $Pr$ at the same $Ra$, but the scaling exponent of its growth with Rayleigh number is reduced. Our analysis of the kurtosis of the locally defined shear Reynolds number demonstrates that the intermittency in the boundary layer is significantly increased for the lower Prandtl number and for sufficiently high Rayleigh number compared to convection in air. This complements our previous findings of enhanced bulk intermittency in low-Prandtl-number convection.
Local boundary layer scales in turbulent Rayleigh–Bénard convection
- Janet D. Scheel, Jörg Schumacher
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- Journal:
- Journal of Fluid Mechanics / Volume 758 / 10 November 2014
- Published online by Cambridge University Press:
- 08 October 2014, pp. 344-373
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We compute fully local boundary layer scales in three-dimensional turbulent Rayleigh–Bénard convection. These scales are directly connected to the highly intermittent fluctuations of the fluxes of momentum and heat at the isothermal top and bottom walls and are statistically distributed around the corresponding mean thickness scales. The local boundary layer scales also reflect the strong spatial inhomogeneities of both boundary layers due to the large-scale, but complex and intermittent, circulation that builds up in closed convection cells. Similar to turbulent boundary layers, we define inner scales based on local shear stress that can be consistently extended to the classical viscous scales in bulk turbulence, e.g. the Kolmogorov scale, and outer scales based on slopes at the wall. We discuss the consequences of our generalization, in particular the scaling of our inner and outer boundary layer thicknesses and the resulting shear Reynolds number with respect to the Rayleigh number. The mean outer thickness scale for the temperature field is close to the standard definition of a thermal boundary layer thickness. In the case of the velocity field, under certain conditions the outer scale follows a scaling similar to that of the Prandtl–Blasius type definition with respect to the Rayleigh number, but differs quantitatively. The friction coefficient $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}c_{\epsilon }$ scaling is found to fall right between the laminar and turbulent limits, which indicates that the boundary layer exhibits transitional behaviour. Additionally, we conduct an analysis of the recently suggested dissipation layer thickness scales versus the Rayleigh number and find a transition in the scaling. All our investigations are based on highly accurate spectral element simulations that reproduce gradients and their fluctuations reliably. The study is done for a Prandtl number of $\mathit{Pr}=0.7$ and for Rayleigh numbers that extend over almost five orders of magnitude, $3\times 10^5\le \mathit{Ra} \le 10^{10}$, in cells with an aspect ratio of one. We also performed one study with an aspect ratio equal to three in the case of $\mathit{Ra}=10^8$. For both aspect ratios, we find that the scale distributions depend on the position at the plates where the analysis is conducted.