Post-Heart Transplantation Lymphoproliferations

Post-transplant lymphoproliferations (PTLDs) are the cancer with the highest incidence after cardiac transplantation. The World Health Organization (WHO) has defined several specific entities: clonal or non-clonal, early, polymorphic or monomorphic. Early PTLDs being generally positive for Epstein-Barr virus (EBV), preventive and preemptive treatments have been proposed; the former did not lead to effective attitudes, unlike preemptive treatment, based on EBV viral load monitoring the first year, which proposes a decrease of the immunosuppression with or without rituximab according to the viral load and the answer to the immunosuppression decrease. The curative treatment of CD20 positive PTLDs, the most frequent form, begins to be codified; it starts with a decrease in immunosuppression and then uses rituximab monotherapy and, depending on the response, either only rituximab or four courses of R-CHOP. By following this management, the incidence of early PTLDs decreases and the treatment of PTLDs provides survivals close to that of other transplant patients

James Webb Space Telescope Optical Simulation Testbed I: Overview and First Results

The James Webb Space Telescope (JWST) Optical Simulation Testbed (JOST) is a tabletop workbench to study aspects of wavefront sensing and control for a segmented space telescope, including both commissioning and maintenance activities. JOST is complementary to existing optomechanical testbeds for JWST (e.g. the Ball Aerospace Testbed Telescope, TBT) given its compact scale and flexibility, ease of use, and colocation at the JWST Science & Operations Center. We have developed an optical design that reproduces the physics of JWST's three-mirror anastigmat using three aspheric lenses; it provides similar image quality as JWST (80% Strehl ratio) over a field equivalent to a NIRCam module, but at HeNe wavelength. A segmented deformable mirror stands in for the segmented primary mirror and allows control of the 18 segments in piston, tip, and tilt, while the secondary can be controlled in tip, tilt and x, y, z position. This will be sufficient to model many commissioning activities, to investigate field dependence and multiple field point sensing & control, to evaluate alternate sensing algorithms, and develop contingency plans. Testbed data will also be usable for cross-checking of the WFS&C Software Subsystem, and for staff training and development during JWST's five- to ten-year mission.Comment: Proceedings of the SPIE, 9143-150. 13 pages, 8 figure

CHOP-21 for the treatment of post-transplant lymphoproliferative disorders following solid organ transplantation

There is no definitive treatment for post-transplant lymphoproliferative disorder (PTLD) that does not respond to reduction of immunosuppression. With a median follow-up of 8.8 years, the current retrospective analysis of standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) in 26 adults with PTLD demonstrated an overall response rate of 65% and median overall and progression-free survivals of 13.9 and 42 months, respectively

Maritime Transportation: Let\u27s Slow Down a Bit

Maritime transportation is a major contributor to the world economy, but has significant social and environmental impacts. Each impact calls for different technical or operational solutions. Amongst these solutions, we found that speed reduction measures appear to mitigate several issues: (1) collision with wildlife; (2) collision with non-living objects; (3) underwater noise; (4) invasive species; and (5) gas emission. We do not pretend that speed reduction is the best solution for each individual issue mentioned in this paper, but we argue that it could be a key solution to significantly reduce these threats all together. Further interdisciplinary research is required to balance private economic costs of speed reduction measures with environmental and social benefits emerging from all mitigated issues

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL