A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to ...determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.
Reinforcement learning for nonstationary problems is a subject of widespread research given that most realistic problems do not exist within static environments. Approaching these problems can ...require significant effort in feature engineering to provide a learning algorithm with enough useful information about the state space to uncover complex system dynamics. As an alternative for problems with sufficient data describing the nonstationary environment, we propose the contextual decomposition Markov decision process (CDMDP) as a collection of stationary sub-problems intended to approximate nonstationary problem dynamics using a linear combination of value functions. We demonstrate the effectiveness of the CDMDP approach with an application in military air battle management. We use a designed computational experiment and analysis of variance to show that a complex, nonstationary learning problem can be effectively approximated with a small set of stationary sub-problems, and that the CDMDP solution significantly improves solution quality over a baseline approach without the need for additional feature engineering. If a researcher suspects that a complex and continuously varying environment can be approximated by a small number of stationary contexts, the CDMDP framework may save significant computational resources and yield decision policies that are much easier to visualize and implement.
•We model a military air battle scenario with a nonstationary Markov decision process.•We decompose a complex problem into a number of smaller sub-problems.•We use a computational experiment to find an effective neural network architecture.•We use a learning algorithm to develop decision policies for autonomous aircraft.•Our approach significantly improves solution quality over a baseline.
Women in Civil War Texas is the first book dedicated to the unique experiences of Texas women during the Civil War. It fills the literary void in Texas women’s history during this time, connects ...Texas women’s lives to southern women’s history, and shares the diversity of experiences of women in Texas during the Civil War. An introductory essay situates the anthology within both Civil War and Texas women’s history. Contributors explore Texas women and their vocal support for secession and in support of a war, coping with their husbands’ wartime absences, the importance of letter-writing as a means of connecting families, and how pro-Union sentiment caused serious difficulties for women. They also analyze the effects of ethnicity, focusing on African American, German, and Tejana women’s experiences. Finally, two essays examine the problem of refugee women in east Texas and the dangers facing western frontier women. These essays develop the historical understanding of what it meant to be a Texas woman during the Civil War and also contribute to a deeper understanding of the complexity of the war and its effects.
The surface Ig on each B-cell lymphoma has unique portions (idiotypes), which can be recognized by the immune system. In this study, we immunized patients against the Ig expressed by their tumor and ...observed their clinical outcomes. After standard chemotherapy, 41 patients with non-Hodgkin's B-cell lymphoma received a series of injections with a vaccine consisting of tumor Ig protein coupled to keyhole limpet hemocyanin and emulsified in an immunologic adjuvant. Subjects were observed for toxicity, immune responses, and tumor status. The median duration of follow-up of all patients is 7.3 years from diagnosis and 5.3 years from the last chemotherapy given before vaccine treatment. Twenty patients (49%) generated specific immune responses against the idiotypes of their tumor Ig. Two patients who had residual disease experienced complete tumor regression in association with the development of these immune responses. The median duration of freedom from disease progression and overall survival of all 20 patients mounting an anti-idiotype immune response are significantly prolonged compared to the patients who did not mount an immune response. Thirty-two patients were in their first remission and nine were in subsequent remissions before beginning vaccine treatments. Analysis of the 32 first remission patients also shows an improved clinical outcome for those patients who mounted a specific immune response compared to those who did not (freedom from progression, 7.9 years v 1.3 years P = .0001; median survival from time of last chemotherapy not yet reached v 7 years, P = .04). This study confirms an earlier report that patients with B-cell lymphoma can be induced to make a specific immune response against the Ig expressed by their own tumor. It further shows that the ability to make such an immune response is correlated with a more favorable clinical outcome. Prospective controlled trials will be needed to prove a causal relationship between anti-idiotype immunity and improved clinical outcome.
Purpose
To examine processes, barriers, and facilitators to sperm banking counseling and decision-making for adolescent males newly diagnosed with cancer from the perspective of clinicians who ...completed Oncofertility communication training. We also identify opportunities for improvement to inform future interventions and implementation.
Methods
A survey (
N
=104) and subsequent focus groups (
N
=15) were conducted with non-physician clinicians practicing in pediatric oncology who completed Oncofertility communication training.
Results
Most survey participants were confident in communicating about the impact of cancer on fertility (
n
=87, 83.7%) and fertility preservation options (
n
=80, 76.9%). Most participants reported never/rarely using a sperm banking decision tool (
n
=70, 67.3%), although 98.1% (
n
=102) said a decision tool with a family-centered approach would be beneficial. Primary themes in the subsequent focus groups included variable processes/workflows (inconsistent approaches to consult initiation; involvement of adolescents, caregivers, and various clinician types; assessment of puberty/sexual experience), structural and psychosocial barriers (cost and logistics, developmental, cultural, clinical acuity/prognosis), and facilitators (educational materials, alternative options for banking). Opportunities and strategies for improvement (including fertility preservation in existing research protocols; additional staffing/resources; oncologist education and buy-in; and development of decision tools) were informed by challenges identified in the other themes.
Conclusion
Barriers to adolescent sperm banking remain, even among clinicians who have completed Oncofertility training. Although training is one factor necessary to facilitate banking, structural and psychosocial barriers persist. Given the complexities of offering sperm banking to pediatric populations, continued efforts are needed to mitigate structural barriers and develop strategies to facilitate decision-making before childhood cancer treatment.
The present study focuses on determining soil fungal community structure in different peanut-cropping sequences by using a high-resolution DNA fingerprinting technique: ribosomal intergenic spacer ...analysis (RISA). This study was initiated to determine fungal community profiles in four peanut-cropping sequences (continuous peanut, 4 years of continuous bahiagrass followed by peanut, peanut-corn-cotton, and peanut-cotton rotations), with a special focus to evaluate whether the profiles under investigation may have also indicated microbial differences that could affect Aspergillus flavus populations. Results indicated 75% similarities among fungal communities from the same cropping sequences as well as with similar times of sampling. Polymerase chain reaction (PCR)-based detection of A. flavus directly from these soils was carried out using A. flavus-specific primers (FLA1 and FLA2) and also through quantitative estimation on A. flavus and A. parasiticus agar medium. Population levels of A. flavus in soil samples ranged from zero to 1.2 × 10(3) CFU g–1 of soil (based on culturable methods); however, the fungus was not detected with A. flavus-specific primers. The minimum threshold limit at which these aflatoxin-producing fungi could be detected from the total soil genomic DNA was determined through artificial inoculation of samples with 10-fold increases in concentrations. The results indicated that a minimum population density of 2.6 × 10(6) CFU g–1 of soil is required for PCR detection in our conditions. These results are useful in further determining the relative population levels of these fungi in peanut soils with other soil fungi. This is a new approach to understanding soil fungal communities and how they might change over time and under different rotation systems.
While little is known about hawksbill turtles Eretmochelys imbricata in the eastern Pacific Ocean, available information suggests that the population has declined substantially in recent decades and ...could be near extirpation in the region. To evaluate the current status of the population more effectively and to determine the feasibility of recovery efforts, a workshop of regional marine turtle specialists was held in June 2008 in Los Cóbanos, El Salvador. An international working group, Iniciativa Carey del Pacífico Oriental (ICAPO; Eastern Pacific Hawksbill Initiative in English), was established to consolidate information, promote conservation projects and raise awareness about the species. We present information derived from the workshop and compiled by the ICAPO working group since that time. Considering only records from 1 January 2007 to 31 May 2009 it appears that El Salvador hosts the majority of known hawksbill turtle nesting activity in the eastern Pacific, with 79.6% (n = 430) of all nesting observation records, and Mexico hosts the majority of records of hawksbill turtles at sea, with 60.3% (n = 44) of all in-water observation records. Although current abundance is very low, the pervasiveness of the species in the region suggests potential for conservation and recovery. Despite a historical paucity of research focusing on this population, the relatively large and steadily increasing number of records as a result of concerted efforts demonstrates the viability of the ICAPO network as an instrument to promote conservation of this species in the eastern Pacific.
Previously, we had isolated by transposon mutagenesis a Legionella pneumophila mutant that appeared defective for intracellular iron acquisition. While sequencing in the proximity of the mini-Tn10 ...insertion, we found a locus that had a predicted protein product with strong similarity to PilB from Pseudomonas aeruginosa. PilB is a component of the type II secretory pathway, which is required for the assembly of type IV pili. Consequently, the locus was cloned and sequenced. Within this 4-kb region were three genes that appeared to be organized in an operon and encoded homologs of P. aeruginosa PilB, PilC, and PilD, proteins essential for pilus production and type II protein secretion. Northern blot analysis identified a transcript large enough to include all three genes and showed a substantial increase in expression of this operon when L. pneumophila was grown at 30 degrees C as opposed to 37 degrees C. The latter observation was then correlated with an increase in piliation when bacteria were grown at the lower temperature. Southern hybridization analysis indicated that the pilB locus was conserved within L. pneumophila serogroups and other Legionella species. These data represent the first isolation of type II secretory genes from an intracellular parasite and indicate that the legionellae express temperature-regulated type IV pili.
The B-cell antigen CD20 is expressed on normal B cells and by nearly all B-cell lymphomas. This nonmodulating antigen provides an excellent target for antibody-directed therapies. A chimeric ...anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-kappa constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8, has been produced for clinical trials. It lyses CD20+ cells in vitro via complement and antibody-dependent cell-mediated lysis. Preclinical studies have shown that the chimeric antibody selectively depletes B cells in blood and lymph nodes in macaque monkeys. In this phase I clinical trial, 15 patients (3 per dose level) with relapsed low-grade B-cell lymphoma were treated with a single dose (10, 50, 100, 250, or 500 mg/m2) of antibody administered intravenously. Treatment-related symptoms correlated with the number of circulating CD20 cells and grade II events consisted of fever (5 patients); nausea (2), rigor (2), orthostatic hypotension (2), bronchospasm (1), and thrombocytopenia (1). No significant toxicities were observed during the 3 months of follow-up. Serum C3, IgG, and IgM levels, neutrophils, and T cells were largely unchanged. At the three higher dose levels, pharmacokinetics of the free antibody showed a serum half-life of 4.4 days (range, 1.6 to 10.5). Levels greater than 10 micrograms/mL persisted in 6 of 9 patients for more than 14 days. No quantifiable immune responses to the infused antibody have been detected. CD20+ B cells were rapidly and specifically depleted in the peripheral blood at 24 to 72 hours and remained depleted for at least 2 to 3 months in most patients. Two-week postinfusion tumor biopsies showed the chimeric antibody bound to tumor cells and a decrease in the percentage of B cells. Tumor regressions occurred in 6 of 15 patients (2 partial and 4 minor responses). The results of this single-dose trial have been used to design a multiple-dose phase I/II study.
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