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Patients with large B-cell lymphoma (LBCL) primary refractory to or relapsed within 12 months of first-line therapy are at high risk for poor outcomes with current standard of care, platinum-based salvage immunochemotherapy and autologous haematopoietic stem cell transplantation (HSCT). Lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has previously demonstrated efficacy and manageable safety in third-line or later LBCL. In this Article, we report a prespecified interim analysis of liso-cel versus standard of care as second-line treatment for primary refractory or early relapsed (within 12 months after response to initial therapy) LBCL. TRANSFORM is a global, phase 3 study, conducted in 47 sites in the USA, Europe, and Japan, comparing liso-cel with standard of care as second-line therapy in patients with primary refractory or early (≤12 months) relapsed LBCL. Adults aged 18–75 years, Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, PET–positive disease per Lugano 2014 criteria, and candidates for autologous HSCT were randomly assigned (1:1), by use of interactive response technology, to liso-cel (100 × 106 CAR+ T cells intravenously) or standard of care. Standard of care consisted of three cycles of salvage immunochemotherapy delivered intravenously—R-DHAP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, two infusions of cytarabine 2000 mg/m2 on day 2, and cisplatin 100 mg/m2 on day 1), R-ICE (rituximab 375 mg/m2 on day 1, ifosfamide 5000 mg/m2 on day 2, etoposide 100 mg/m2 on days 1–3, and carboplatin area under the curve 5 [maximum dose of 800 mg] on day 2), or R-GDP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, gemcitabine 1000 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1)—followed by high-dose chemotherapy and autologous HSCT in responders. Primary endpoint was event-free survival, with response assessments by an independent review committee per Lugano 2014 criteria. Efficacy was assessed per intention-to-treat (ie, all randomly assigned patients) and safety in patients who received any treatment. This trial is registered with ClinicalTrials.gov, NCT03575351, and is ongoing. Between Oct 23, 2018, and Dec 8, 2020, 232 patients were screened and 184 were assigned to the liso-cel (n=92) or standard of care (n=92) groups. At the data cutoff for this interim analysis, March 8, 2021, the median follow-up was 6·2 months (IQR 4·4–11·5). Median event-free survival was significantly improved in the liso-cel group (10·1 months [95% CI 6·1–not reached]) compared with the standard-of-care group (2·3 months [2·2–4·3]; stratified hazard ratio 0·35; 95% CI 0·23–0·53; stratified Cox proportional hazards model one-sided p<0·0001). The most common grade 3 or worse adverse events were neutropenia (74 [80%] of 92 patients in the liso-cel group vs 46 [51%] of 91 patients in the standard-of-care group), anaemia (45 [49%] vs 45 [49%]), thrombocytopenia (45 [49%] vs 58 [64%]), and prolonged cytopenia (40 [43%] vs three [3%]). Grade 3 cytokine release syndrome and neurological events, which are associated with CAR T-cell therapy, occurred in one (1%) and four (4%) of 92 patients in the liso-cel group, respectively (no grade 4 or 5 events). Serious treatment-emergent adverse events were reported in 44 (48%) patients in the liso-cel group and 44 (48%) in the standard-of-care group. No new liso-cel safety concerns were identified in the second-line setting. There were no treatment-related deaths in the liso-cel group and one treatment-related death due to sepsis in the standard-of-care group. These results support liso-cel as a new second-line treatment recommendation in patients with early relapsed or refractory LBCL. Celgene, a Bristol-Myers Squibb Company.

Background and Objectives Lisocabtagene maraleucel (liso-cel) is a CD19-directed, defined composition, 4-1BB chimeric antigen receptor (CAR) T-cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. Large between-subject variability has been noted with CAR T-cell therapies; patient characteristics might contribute to CAR T-cell expansion variability. We developed a population cellular kinetic model to characterize the kinetics of the liso-cel transgene, via quantitative polymerase chain reaction assessment after intravenous infusion of liso-cel, and to understand covariates that might influence liso-cel kinetics in individual patients. Methods We employed nonlinear mixed-effects modeling to develop a population cellular kinetic model for liso-cel. The population cellular kinetic analysis was performed using 2524 post-infusion transgene observations from 261 patients with relapsed/refractory large B-cell lymphoma who were treated with a single dose of liso-cel in TRANSCEND NHL 001. Covariates for the analysis included baseline intrinsic factors such as age, baseline disease characteristics, and liso-cel and coadministration factors. Results Liso-cel cellular kinetics were well described by a piecewise model of cellular growth kinetics that featured lag, exponential growth, and biexponential decay phases. Population means (95% confidence interval) of lag phase duration, doubling time, time to maximum levels, initial decline half-life, and terminal half-life were 3.27 (2.71–3.97), 0.755 (0.667–0.821), 9.29 (8.81–9.70), 5.00 (4.15–5.90), and 352 (241–647) days, respectively. The magnitude of effect on liso-cel expansion metrics demonstrated that the covariate associations were smaller than the residual between-subject variability in the population. Conclusions The covariates tested were not considered to have a meaningful impact on liso-cel kinetics. Clinical Trial Registration NCT02631044.

Sport programs have been widely studied for their efficacy in helping youth develop important social, psychological, and physical skills. Extensive research has explored the challenges related to design, implementation, and evaluation of sport programs with a developmental focus. However, when designing sport programs specifically tailored for youth from vulnerable backgrounds, the challenges become multiplied, particularly when accounting for barriers that exist before the program starts. The following article describes best practices for gaining access to non-traditional, hard-to-access environments, such as foster care systems, juvenile detention centers, youth residential mental health facilities, and programs situated in high-risk communities. Recommendations are provided for the initial phase of sport program development for vulnerable populations, including protecting youth, choosing appropriate sport content, and addressing barriers in the research process. Generally, these best practices are applicable for the development of any youth program. However, this article provides context-specific guidance and precautions that should be considered to protect and foster the well-being and welfare of youth from highly vulnerable populations.

As a comprehensive nationwide system, the Food and Agricultural Education Information System (FAEIS) provides empirical data and analyses for planning, benchmarking, and coordinating efforts, directed towards supporting higher education in the food, human, agricultural, and natural resource sciences. FAEIS (http://faeis.usda.gov/) is an accessible resource for data users that includes faculty, higher education administrators, government officials, industry professionals, and the general public to strengthen higher education programs and is sponsored by the U. S. Department of Agriculture (USDA). Recently 2008 marked one of the best years for FAEIS reporting with 100% reporting from nearly all of our sponsoring associations: Association of Public and Land-Grant Universities (APLU), formally National Association of State Universities and Land-Grant Colleges (NASULGC) ; American Association of State Colleges of Agriculture and Renewable Resources (AASCARR); Association of American Veterinary Medical Colleges (AAVMC); Board on Human Sciences (BOHS); Council on Administrators of Family and Consumer Sciences (CAFCS); Society of American Foresters (SAF); and National Association of University Forest Resources Programs (NAUFRP). This article seeks to expand awareness of FAEIS, discuss the data collection process, and provide readers with examples of how they can use FAEIS.

This thesis explores aspects of exciton coupling to vibrational modes of colloidal CdSe semiconductor nanocrystals (NCs) using photoluminescence and Raman spectroscopies.The first part explores exciton coupling to the internal CdSe longitudinal optical phonon mode. CdSe NCs typically exhibit small Stokes shifts and narrow emissive linewidths in the visible region which stem from the strong excitonic confinement in the core of the nanocrystal. However, in the case of ~2nm CdSe NCs, a secondary broad emissive feature with a large Stokes shift can be observed in addition to the commonly observed narrow emissive feature. This feature is attributed to excitonic surface trapping. The differences in linewidths and Stokes shifts of these two features is rationalized by the extent to which they couple to the internal CdSe longitudinal optical phonon mode. This hypothesis is evaluated through comparison of a simple model with experimental measurements of the emission lineshape as a function of temperature. The consequence of strong phonon coupling on the chromaticity and quantum yield temperature dependence is also examined.In the second part, Resonance Raman spectroscopy is used to study exciton electronic state coupling to CdSe NC ligand vibrational modes. This is accomplished via a simple ligand exchange procedure with a well-studied Raman probe such as thiophenol or a thiophenol substituted derivative, which has the additional advantage of quenching CdSe NC photoluminescence. Recent theoretical and computational studies have posited that such exciton vibrational couplings can lead to Raman signal enhancements. By employing a set of thiophenol derivatives of various point group symmetries, the Raman enhancements of totally symmetric modes are attributed to Franck-Condon coupling. The possibility of Herzberg-Teller coupling leading to Raman signal enhancements of non-totally symmetric modes is also investigated.

Density management diagrams (DMDs) are widely used within the North American forestry community. DMDs, as traditionally implemented, have some limitations, including lack of automation, poor age and mortality accounting, and inflexible product yield reporting. We propose a model-based approach to circumvent these limitations. Resinosa, an interactive DMD for Lake States red pine, takes this approach. We describe the stand-level, self-thinning-constrained growth model that is the basis for Resinosa to illustrate our arguments. Resinosa allows foresters to make quick and easy comparisons among management regimes.

This article describes the construction and application of a stand-level merchantable yield equation for red pine in the Lake States. The equation predicts merchantable cubic foot volume for the stand based on minimum dbh and top size thresholds defined by the user. The merchantable yield equation can be used to model the merchandizing of user-defined products from stands given total stand volume, quadratic mean dbh, and the number of trees per acre. Also presented is an equation for estimating the distribution of trees per acre within a stand by dbh class. The equation predicts number of trees per acre larger than a specified dbh given the surviving number of trees per acre and mean dbh. The trees per acre equation can be used to describe the distribution of both diameter and basal area given number of trees per acre and quadratic mean dbh.