A decade of living lobar lung transplantation: recipient outcomes

AbstractObjectiveLiving lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation.MethodsOne hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years).ResultsThe primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients (P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50).ConclusionThese results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations

BAFopathies\u27 DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening

Laser–Solid Interaction Studies Enabled by the New Capabilities of the iP2 BELLA PW Beamline

The new capabilities of the short focal length, high intensity beamline, named iP2, at the BELLA Center will extend the reach of research in high energy density science, including accessing new regimes of high gradient ion acceleration and their applications. This 1 Hz system will provide an on-target peak intensity beyond 1021 W/cm2 with a temporal contrast ratio of <10−14 that will be enabled by the addition of an on-demand double plasma mirror setup. An overview of the beamline design and the main available diagnostics are presented in this paper as well as a selection of accessible research areas. As a demonstration of the iP2 beamline's capabilities, we present 3D particle-in-cell simulations of ion acceleration in the magnetic vortex acceleration regime. The simulations were performed with pure hydrogen targets and multi-species targets. Proton beams with energy up to 125 MeV and an approximately 12° full angle emission are observed as preplasma scale length and target tilt are varied. The number of accelerated protons is on the order of 109/MeV/sr for energies above 60 MeV

Online charge measurement for petawatt laser-driven ion acceleration

Laser-driven ion beams have gained considerable attention for their potential use in multidisciplinary research and technology. Preclinical studies into their radiobiological effectiveness have established the prospect of using laser-driven ion beams for radiotherapy. In particular, research into the beneficial effects of ultrahigh instantaneous dose rates is enabled by the high ion bunch charge and uniquely short bunch lengths present for laser-driven ion beams. Such studies require reliable, online dosimetry methods to monitor the bunch charge for every laser shot to ensure that the prescribed dose is accurately applied to the biological sample. In this paper, we present the first successful use of an Integrating Current Transformer (ICT) for laser-driven ion accelerators. This is a noninvasive diagnostic to measure the charge of the accelerated ion bunch. It enables online estimates of the applied dose in radiobiological experiments and facilitates ion beam tuning, in particular, optimization of the laser ion source, and alignment of the proton transport beamline. We present the ICT implementation and the correlation with other diagnostics, such as radiochromic films, a Thomson parabola spectrometer, and a scintillator

A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline.

Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2&nbsp;MeV energy at 0.2&nbsp;Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10&nbsp;mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35&nbsp;Gy at ultra-high instantaneous dose rates of 107&nbsp;Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7&nbsp;Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect