Search

We present detailed experimental and theoretical analysis for both constant-wave and pulsed excitation for a variety of real bilayer organic light-emitting diodes (LEDs). We find from experiment and simulation that the recombination zone may be moved about the polymer-polymer heterojunction as a function of the applied voltage. We suggest a method for spectrally resolving the emission of both polymers of a bilayer LED as a function of time, and show that these results are in good agreement with time-dependent simulation results. The simulation model takes into account both the discontinuities in energy levels and mobilities across the polymer-polymer heterojunction. [ABSTRACT FROM AUTHOR]

Presents information on a study which analyzed the pulsed excitation of polymer light emitting diodes. Experimental details; Results and discussion; Conclusions.

Abstract: CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Of 12 patients, 10 (83%) achieved a measurable residual disease (MRD)-negative complete remission at 2 months after infusion. Of 10 responding patients, 5 had emergence of MRD (n = 2) or relapse (n = 3) with CD19- and CD22-expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months, there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95% confidence interval [CI], 41%-91%) at 6 and 12 months. The 6- and 12-month event-free survival rates were 75% (95% CI, 41%-91%) and 60% (95% CI, 23%-84%), respectively. These data suggest dual targeting with cotransduction may prevent antigen-negative relapse after CAR T-cell therapy., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia., Methods: We enrolled paediatric or adult patients in two ongoing, multicentre, phase 1 clinical trials to evaluate the safety and antileukaemic activity of UCART19. All patients underwent lymphodepletion with fludarabine and cyclophosphamide with or without alemtuzumab, then children received UCART19 at 1·1-2·3 × 10 6 cells per kg and adults received UCART19 doses of 6 × 10 6 cells, 6-8 × 10 7 cells, or 1·8-2·4 × 10 8 cells in a dose-escalation study. The primary outcome measure was adverse events in the period between first infusion and data cutoff. These studies were registered at ClinicalTrials.gov, NCT02808442 and NCT02746952., Findings: Between June 3, 2016, and Oct 23, 2018, seven children and 14 adults were enrolled in the two studies and received UCART19. Cytokine release syndrome was the most common adverse event and was observed in 19 patients (91%); three (14%) had grade 3-4 cytokine release syndrome. Other adverse events were grade 1 or 2 neurotoxicity in eight patients (38%), grade 1 acute skin graft-versus-host disease in two patients (10%), and grade 4 prolonged cytopenia in six patients (32%). Two treatment-related deaths occurred; one caused by neutropenic sepsis in a patient with concurrent cytokine release syndrome and one from pulmonary haemorrhage in a patient with persistent cytopenia. 14 (67%) of 21 patients had a complete response or complete response with incomplete haematological recovery 28 days after infusion. Patients not receiving alemtuzumab (n=4) showed no UCART19 expansion or antileukaemic activity. The median duration of response was 4·1 months with ten (71%) of 14 responders proceeding to a subsequent allogeneic stem-cell transplant. Progression-free survival at 6 months was 27%, and overall survival was 55%., Interpretation: These two studies show, for the first time, the feasibility of using allogeneic, genome-edited CAR T cells to treat patients with aggressive leukaemia. UCART19 exhibited in-vivo expansion and antileukaemic activity with a manageable safety profile in heavily pretreated paediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. The results this study are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR-T-cell therapy is unavailable., Funding: Servier., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC (0-∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23-1.74), and the hazard ratio for low engraftment was 0.61 (0.36-1.04). A cumulative AUC (0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC (0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease., (© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

We examine the theoretical motivations for long-lived particle (LLP) signals at the LHC in a comprehensive survey of standard model (SM) extensions. LLPs are a common prediction of a wide range of theories that address unsolved fundamental mysteries such as naturalness, dark matter, baryogenesis and neutrino masses, and represent a natural and generic possibility for physics beyond the SM (BSM). In most cases the LLP lifetime can be treated as a free parameter from the [Formula: see text]m scale up to the Big Bang Nucleosynthesis limit of [Formula: see text] m. Neutral LLPs with lifetimes above [Formula: see text]100 m are particularly difficult to probe, as the sensitivity of the LHC main detectors is limited by challenging backgrounds, triggers, and small acceptances. MATHUSLA is a proposal for a minimally instrumented, large-volume surface detector near ATLAS or CMS. It would search for neutral LLPs produced in HL-LHC collisions by reconstructing displaced vertices (DVs) in a low-background environment, extending the sensitivity of the main detectors by orders of magnitude in the long-lifetime regime. We study the LLP physics opportunities afforded by a MATHUSLA-like detector at the HL-LHC, assuming backgrounds can be rejected as expected. We develop a model-independent approach to describe the sensitivity of MATHUSLA to BSM LLP signals, and compare it to DV and missing energy searches at ATLAS or CMS. We then explore the BSM motivations for LLPs in considerable detail, presenting a large number of new sensitivity studies. While our discussion is especially oriented towards the long-lifetime regime at MATHUSLA, this survey underlines the importance of a varied LLP search program at the LHC in general. By synthesizing these results into a general discussion of the top-down and bottom-up motivations for LLP searches, it is our aim to demonstrate the exceptional strength and breadth of the physics case for the construction of the MATHUSLA detector.

Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in relapsed/refractory acute lymphoblastic leukemia (ALL) 1-5 , but toxicity, including cytokine-release syndrome (CRS) and neurotoxicity, limits broader application. Moreover, 40-60% of patients relapse owing to poor CAR T cell persistence or emergence of CD19 - clones. Some factors, including the choice of single-chain spacer 6 and extracellular 7 and costimulatory domains 8 , have a profound effect on CAR T cell function and persistence. However, little is known about the impact of CAR binding affinity. There is evidence of a ceiling above which increased immunoreceptor affinity may adversely affect T cell responses 9-11 . We generated a novel CD19 CAR (CAT) with a lower affinity than FMC63, the high-affinity binder used in many clinical studies 1-4 . CAT CAR T cells showed increased proliferation and cytotoxicity in vitro and had enhanced proliferative and in vivo antitumor activity compared with FMC63 CAR T cells. In a clinical study (CARPALL, NCT02443831 ), 12/14 patients with relapsed/refractory pediatric B cell acute lymphoblastic leukemia treated with CAT CAR T cells achieved molecular remission. Persistence was demonstrated in 11 of 14 patients at last follow-up, with enhanced CAR T cell expansion compared with published data. Toxicity was low, with no severe CRS. One-year overall and event-free survival were 63% and 46%, respectively.

Objective: Research suggests that weight suppression (WS) is linked to non-suicidal self-injury (NSSI) and that drive for thinness and depression may explain this association. We conducted a proof-of-concept study using a randomized control trial design to determine if improving body esteem and reducing depressive symptoms reduced NSSI in individuals with WS., Method: Weight suppressed participants (N = 60) who engaged in NSSI were recruited from the community and randomly assigned to an on-line intervention or control condition. The on-line intervention was adapted from a cognitive-dissonance intervention originally designed to reduce thin-ideal internalization in females to an intervention to reduce internalization of unhealthy body ideals in both genders. Participants' weight/shape concerns, depressive symptoms, and NSSI were assessed at pre- and post-intervention, or at baseline and 2-week follow-up for controls., Results: Compared to controls, participants in the treatment condition reported greater decreases in likelihood of future NSSI [Cohen's d (95% CI) = -0.38 (-0.90-0.15)], weight/shape concerns [-1.19 (-1.75 to -0.62)], depressive symptoms [-1.00 (-1.56 to -0.45)], and significant improvements in appearance [1.27 (0.70-1.84)] and weight esteem [1.38 (0.80-1.96)]., Discussion: Future work could test this intervention in a larger trial with an active alternative treatment condition., (© 2019 Wiley Periodicals, Inc.)

Objective: Pressures for men to conform to a lean, muscular ideal have, in part, contributed to eating disorder and muscle dysmorphia symptoms, yet few programs have been developed and empirically evaluated to help men. This study investigated the acceptability and efficacy of a cognitive dissonance-based (DB) intervention in reducing eating disorder and muscle dysmorphia risk factors in men with body dissatisfaction., Method: Men were randomized to a two-session DB intervention (n = 52) or a waitlist control condition (n = 60). Participants completed validated measures assessing eating disorder risk factors preintervention, postintervention, and at 1-month follow-up., Results: Program ratings indicated high acceptability. The DB condition demonstrated greater decreases in body-ideal internalization, dietary restraint, bulimic symptoms, drive for muscularity, and muscle dysmorphia symptoms compared with controls (p values <  .02; between-condition Cohen's d = .30-1.11) from pre- to postintervention. At one-month follow-up, the DB condition demonstrated significantly lower scores for all variables (p values <  .03; between-condition d = .29-1.16). Body-ideal internalization mediated intervention outcomes on bulimic and muscle dysmorphia symptoms., Discussion: Results support the acceptability and efficacy of The Body Project: More Than Muscles up to 1-month postintervention and should be examined against active control conditions., (© 2017 Wiley Periodicals, Inc.)

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19 + B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology., (Copyright © 2017, American Association for the Advancement of Science.)

We present a new solution to the electroweak hierarchy problem. We introduce N copies of the standard model with varying values of the Higgs mass parameter. This generically yields a sector whose weak scale is parametrically removed from the cutoff by a factor of 1/sqrt[N]. Ensuring that reheating deposits a majority of the total energy density into this lightest sector requires a modification of the standard cosmological history, providing a powerful probe of the mechanism. Current and near-future experiments can explore much of the natural parameter space. Furthermore, supersymmetric completions that preserve grand unification predict superpartners with mass below m&#95;{W}M&#95;{pl}/M&#95;{GUT}∼10  TeV.