Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P =0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P =0.049), improved somatic growth ( P =0.0005), reduced heart failure status ( P =0.003), and lower incidence of coil occlusion for collaterals ( P =0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01273857.
SUMMARYA new variational data assimilation system for a non-hydrostatic model is being developed at the Japan Meteorological Agency (JMA) for operational use. Known as the JMA non-hydrostatic model variational data assimilation (JNoVA) system, it mainly functions as a four-dimensional variational data assimilation system, although it has an option to be used as a three-dimensional system.The set of control variables consists of initial conditions of unbalanced horizontal winds, large-scale components of potential temperature and surface pressure, unbalanced temperature and pseudo relative humidity. In the control variable transformation, hydrostatic balance and geostrophic balance are considered explicitly and the effect of the surface friction is also considered implicitly. When calculating the background-error covariances by the NMC method, a low-pass filter is introduced to remove noise in potential temperature and surface pressure that degrades the quality of the balanced winds. The cut-off wavelength of the low-pass filter is set to 300 km, which is the scale at which the model's kinetic energy spectrum transits to the shallower slope characterizing mesoscale motions.An adjoint model of the JMA non-hydrostatic model has been developed from scratch by hand for this system. Although some of the physics are simplified, all physical processes except the radiation are considered.A preliminary data assimilation experiment with the JNoVA has been done for a heavy rainfall event. The results show that the quantitative precipitation forecast (in terms of the intensity, timing and position of the event) from the analysis by the JNoVA is improved over the forecast from the analysis by a four-dimensional variational system that employs the JMA hydrostatic spectral model.
The Meteorological Research Institute of the Japan Meteorological Agency has developed a cloudresolving nonhydrostatic 4-dimensional variational assimilation system (NHM-4DVAR), based on the Japan Meteorological Agency Nonhydrostatic Model (JMA-NHM), in order to investigate the mechanism of heavy rainfall events induced by mesoscale convective systems (MCSs). A horizontal resolution of the NHM-4DVAR is set to 2 km to resolve MCSs, and the length of the assimilation window is 1-hour. The control variables of the NHM-4DVAR are horizontal wind, vertical wind, nonhydrostatic pressure, potential temperature, surface pressure and pseudo relative humidity. Perturbations to the dynamical processes, and the advection of water vapor are considered, but these to the other physical processes are not taken into account.The NHM-4DVAR is applied to the heavy rainfall event observed at Nerima, central part of Tokyo metropolitan area, on 21 July 1999. Doppler radar's radial wind data, Global Positioning System's precipitable water vapor data, and surface temperature and wind data are assimilated as high temporal and spatial resolution data. The Nerima heavy rainfall is well reproduced in the assimilation and subseCorresponding author: Takuya Kawabata, Meteorological Research Institute, 1-1 Nagamine, Tsukuba, Ibaraki 305-0052, Japan. E-mail: tkawabat@mri-jma.go.jp 1 Present affiliation: Frontier Research Center for Global Change, Japan Agency for Marine-Earth Science and Technology, Yokohama, Japan.( 2007, Meteorological Society of Japan quent forecast, with respect to time sequence of 10-minute rainfall amount. The formation mechanism of the Nerima heavy rainfall is clarified from this study. A surface convergence line of horizontal winds was made of a southerly sea breeze and north-easterly winds over the Kanto plain around Nerima. Since the rise of temperature over the northern part of the Kanto plain was suppressed, due to a shield of clouds against sunshine, the difference of temperature between the convergence line and its northern side became large. Consequently, the wind convergence was enhanced around Nerima. An air with high equivalent potential temperature was lifted over this enhanced convergence line to generate cumulonimbi that caused the Nerima heavy rainfall.
A cloud-resolving nonhydrostatic four-dimensional variational data assimilation system (NHM-4DVAR) was modified to directly assimilate radar reflectivity and applied to a data assimilation experiment using actual observations of a heavy rainfall event. Modifications included development of an adjoint model of the warm rain process, extension of control variables, and development of an observation operator for radar reflectivity.The responses of the modified NHM-4DVAR were confirmed by single-observation assimilation experiments for an isolated deep convection, using pseudo-observations of rainwater at the initial and end times of the data assimilation window. The results showed that the intensity of convection could be adjusted by assimilating appropriate observations of rainwater near the convection and that undesirable convection could be suppressed by assimilating small or no reflectivity.An assimilation experiment using actual observations of a local heavy rainfall in the Tokyo, Japan, metropolitan area was conducted with a horizontal resolution of 2 km. Precipitable water vapor derived from global positioning system data was assimilated at 5-min intervals within 30-min assimilation windows, and surface and wind profiler data were assimilated at 10-min intervals. Doppler radial wind and radar-reflectivity data below the elevation angle of 5.48 were assimilated at 1-min intervals.The 4DVAR assimilation reproduced a line-shaped rainband with a shape and intensity consistent with the observation. Assimilation of radar-reflectivity data intensified the rainband and suppressed false convection. The simulated rainband lasted for 1 h in the extended forecast and then gradually decayed. Sustaining the low-level convergence produced by northerly winds in the western part of the rainband was key to prolonging the predictability of the convective system.
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