Despite the availability of multiple therapeutic regimens, without a stem cell transplant, chronic lymphocytic leukemia (CLL) remains an incurable disease. A dramatic response rate with intensive ...chemo-immunotherapy in patients with CLL is frequently associated with irreversible long term consequences to the bone marrow, limiting further therapeutic options. For this reason we have initiated a clinical trial combining Rituximab (RIT) and Alemtuzumab (ALEM), two monoclonal antibodies with established activity and side effects profiles, as an initial therapy for patients with CLL requiring intervention.
Methods: Data is available on 20 out of 21 enrolled patients. Therapy duration is 18 weeks. Subcutaneous (SQ) ALEM dose escalation: 3 mg - 10 mg - 30 mg on days 1, 3, 5, followed by the 30 mg Monday, Wednesday and Friday for 17 weeks. RIT at a dose of 375 mg/m2/dose IV is administered every other week staring on the 3d week for 8 doses. All patients received PCP, herpes virus, and fungal prophylaxis as well as CMV viral DNA monitoring. Responses were based on NCI-WG 1996 criteria; however, lymphadenopathy and organomegaly were also assessed by serial CT scans. Minimal residual disease (MRD) was measured in peripheral blood and bone marrow aspirate using flow cytometry for CD19+/CD5+/CD23 lymphocytes.
Patients' characteristics: Since September 2005, 21 patients have been enrolled and 20 completed the therapy. All patients met ECOG criteria for requiring treatment. Median age was 54 years (28 – 74) with 12 males and 8 females; 19 Caucasian and 1 African American. The median time from the diagnosis to treatment was 21.5 months (2–144 months). Clinical stage (Rai) was I in 2 patients, II in 8 patients, III in 4, and IV in 6 patients. Median β2 microglobulin was 3.23 (0.34–15.3). Median WBC was 56 x109/L (17.4 – 157.6), Hgb 12.6 g/dL (10 – 14.7), and platelet count 172 x 109/L (66 – 307). Cytogenetic analysis, by FISH panel, was 13q- in 7, trisomy 12 in 6, and 13q-/11q- in 3, 11q- in 1, 11q-/p53/13q- in 1, and 13q-/11q-/6q- in 1 patient. Half of the patients were Zap70+ and 3 patients were CD38+. Mutational analysis is pending.
Results: Based on the NCI-WG 1996 criteria, 15 patients (75%) achieved CR, 3 patients (15%) achieved PR, and 2 patients (10%) had stable disease. With utilization of CT scans responses were: 8 CR (40%), 9 PR (45%), and 3 SD (15%). At the completion of the study 14 patients (70%) had no evidence of MRD by flow cytometry. Median duration of the response has not been reached with a median follow-up of 20 months (1–31+). All 5 patients with 11q- achieved CR based on the NCI-WG 96 criteria. Three patients (15%) required alternative therapy for the disease progression at 4, 24, and 27 months after the completion of study.
Six patients (30%), all of whom were baseline CMV IgG+, had CMV reactivation by PCR. Two of them developed symptom of malaise and required hospitalization, none suffered organ involvement, and all of them cleared the infection with valgancyclovir administration. One patient suffered neutropenic fever requiring empiric antibiotic therapy followed by Clostridium difficile and adenovirus infections. No other serious infectious complications were documented.
All patients developed grade 1–2 skin rash at the site of ALEM injection after the 1st dose of 3mg only; none required intervention. All patients developed grade 3–4 lymphopenia; neutropenia: grade 2 in 3, grade 3 in 5, and grade 4 in 3 patients; anemia: grade 1 in 9, grade 2 in 2 patients; thrombocytopenia: grade 1 in 8, grade 2 in 4, and grade 3 in 3 patients.
Seven patients have not achieved full T cell recovery (CD4 >200) by 1, 4, 5, 7, 12, and 18 months. The other 13 patients achieved T cell recovery by 1 (n=2), 4 (n=2), 6 (n=1), 7 (n=2), 9 (n=1), 10 (n=1), 15 (n=1), 16 (n=2), and 22 months. All of the patients who suffered CMV reactivation achieved faster T cell recovery than those who did not (median time 5 vs. 22 months). Two patients developed clinically significant autoimmune hemolytic anemia and none suffered Richter's transformation. No death occurred.
Discussion: Combination of ALEM and RIT is well tolerated and active regimen for patients with CLL and may represent a viable alternative to the combination chemotherapy.
Human activity recognition (HAR) is a time series classification task that focuses on identifying the motion patterns from human sensor readings. Adequate data is essential but a major bottleneck for ...training a generalizable HAR model, which assists customization and optimization of online web applications. However, it is costly in time and economy to collect large-scale labeled data in reality, i.e., the low-resource challenge. Meanwhile, data collected from different persons have distribution shifts due to different living habits, body shapes, age groups, etc. The low-resource and distribution shift challenges are detrimental to HAR when applying the trained model to new unseen subjects. In this paper, we propose a novel approach called Diverse and Discriminative representation Learning (DDLearn) for generalizable low-resource HAR. DDLearn simultaneously considers diversity and discrimination learning. With the constructed self-supervised learning task, DDLearn enlarges the data diversity and explores the latent activity properties. Then, we propose a diversity preservation module to preserve the diversity of learned features by enlarging the distribution divergence between the original and augmented domains. Meanwhile, DDLearn also enhances semantic discrimination by learning discriminative representations with supervised contrastive learning. Extensive experiments on three public HAR datasets demonstrate that our method significantly outperforms state-of-art methods by an average accuracy improvement of 9.5% under the low-resource distribution shift scenarios, while being a generic, explainable, and flexible framework. Code is available at: https://github.com/microsoft/robustlearn.
The radiant characters of low clouds and heavy fog and basic principles of detection by remote sensing are introduced in this paper. The present situation and methods of detecting low clouds and ...heavy fog by remote sensing using meteorological satellite data are summarized and the existent problems in this field are discussed at last.
Surface Electromyography (sEMG) based gesture recognition has gained significant attention in the fields of medical rehabilitation and entertainment. However, sEMG exhibits strong user-dependent ...properties among users with different physiological states, limiting the generalization and personalization of existing models. Although incremental learning methods can help the model balance the knowledge learned from old and new users, the existing incremental learning literature lacks attempts at sEMG gesture recognition. This paper fills these gaps and proposes the incremental learning-based cross-user sEMG gesture recognition framework (IncreEGR), to explore the catastrophic forgetting challenges in cross-user sEMG data. IncreEGR consists of two parts: a sampling method based on the center of features (CoF) and discrepancy-based distillation learning (DDL). CoF samples and saves representative user data and replays them during subsequent training processes to ensure that the model can review previous knowledge. DDL aligns the features extracted from the old and new models using a Gaussian kernel-based distance constraint to help the model overcome catastrophic forgetting. We conduct experiments on the benchmark sEMG gesture recognition dataset (i.e., the Ninapro dataset) to verify the effectiveness of IncreEGR. The experimental results demonstrate that our proposed IncreEGR method successfully balances the knowledge between new and old users and achieves the best recognition performance.
Glucocorticoid (GC) is an effective anti-myeloma agent by directly inducing apoptosis and growth inhibition in myeloma cells. The anti-myeloma action of GC is mediated by its intracellular receptor, ...the glucocorticoid receptor (GR). The response to GC is variable among myeloma patients and resistance to glucocorticoid treatment develops almost invariably. The mechanism regulating glucocorticoid-sensitivity in not well understood, although it has been hypothesized that the regulation might occur at both the receptor (GR) and post-receptor level. In MM.1 myeloma cell lines, we observed significant down-regulation of GR expression as the cells develop GC-resistance, suggesting that GR expression level is an important determinant of GC-response. Here we present evidence that GR expression level directly correlates with the clinical outcome in myeloma patients who were treated with GC-containing regimens. First, using a quantitative real-time PCR analysis, we performed a retrospective analysis of GR gene expression on bone marrow plasma cell samples from 35 patients with newly diagnosed myeloma who were then treated on the ECOG study E1A00. This is a phase 3 trial which randomized patients to dexamethasone (dex) alone vs. dex in combination with thalidomide. Pre-treatment expression levels of GR-alpha, GR-beta and GR-P splicing isoforms were measured for 35 patients, of whom, 10 had post-treatment samples available. Interestingly, a large variation of the GR expression levels was observed across the patient samples, with the GR-alpha being the predominant isoform. However, a clear correlation between GR expression and treatment response was not seen, likely due to the small sample size. To access a larger patient pool, we retrospectively analyzed the GR expression levels using the cDNA microarray data from the Arkansas group on 351 newly diagnosed myeloma patients treated with Total Therapy 2, of which dexamethasone was an essential component throughout the treatment course. Of the 351 patients, both event-free (EFS) and overall survivals (OS) were compared between 49 patients (14%) with low levels of GR expression and the rest (86%) with high levels of GR expression. Strikingly, the cases with low levels of GR expression were associated with statistically significantly worse EFS and OS compared to those with high levels of GR expression, with the 5-year EFS of 20% vs. 52% and OS of 34% vs. 68%, P < 0.01. In summary, we have shown for the first time that the baseline level of glucocorticoid receptor expression in newly diagnosed myeloma patients predicts their clinical response to GC-containing regimen and the overall clinical outcome.
Communication based train control (CBTC), which has the advantage of high-precision train positioning without relying on track circuit and realizing real time train-ground wireless communication, has ...been widely adopted in urban rail transit system. Studying the technical development of CBTC is of great significance for comparing the characteristics and differences of relevant technologies, and mastering these technologies, so as to ensure the operation safety of urban rail transit system and improve its operation efficiency. By considering that Japan started early in the development of rail transit system, and Nippon Signal company is a well-known enterprise in the field of rail transit signal control, in this paper, Nippon Signal company has been set as the target enterprise to understand the development trend of CBTC, its patent development context has been analyzed, the most important technologies reflected in its innovation patents applied including train-borne devices, ground devices, train control system and train have also been discussed in detail.
Human activity recognition (HAR) is a time series classification task that focuses on identifying the motion patterns from human sensor readings. Adequate data is essential but a major bottleneck for ...training a generalizable HAR model, which assists customization and optimization of online web applications. However, it is costly in time and economy to collect large-scale labeled data in reality, i.e., the low-resource challenge. Meanwhile, data collected from different persons have distribution shifts due to different living habits, body shapes, age groups, etc. The low-resource and distribution shift challenges are detrimental to HAR when applying the trained model to new unseen subjects. In this paper, we propose a novel approach called Diverse and Discriminative representation Learning (DDLearn) for generalizable low-resource HAR. DDLearn simultaneously considers diversity and discrimination learning. With the constructed self-supervised learning task, DDLearn enlarges the data diversity and explores the latent activity properties. Then, we propose a diversity preservation module to preserve the diversity of learned features by enlarging the distribution divergence between the original and augmented domains. Meanwhile, DDLearn also enhances semantic discrimination by learning discriminative representations with supervised contrastive learning. Extensive experiments on three public HAR datasets demonstrate that our method significantly outperforms state-of-art methods by an average accuracy improvement of 9.5% under the low-resource distribution shift scenarios, while being a generic, explainable, and flexible framework. Code is available at: https://github.com/microsoft/robustlearn.
Novel flexible nanogenerators Qing-Tang Xue; He Tian; Zhe Wang ...
2014 IEEE International Conference on Electron Devices and Solid-State Circuits,
2014-June
Conference Proceeding
In this paper, three kinds of flexible nanogenerators are introduced, the first one is electrostatic nanogenerator using graphene oxide film, the second one is nanogenerator made of ZnO nanoparticles ...and multi-wall carbon nanotube with polydimethylsiloxane, the third one is piezoelectric nanogenerator based on a new type piezoelectric material 0.9525(K 0.5 Na 0.5 NbO 3 )-0.0475LiTaO 3 (KNN-LTS) nanopowder. These three nanogenerators can be used to harvest energy. Furthermore, these kinds of nanogenerators have some advantages, such as the simple process of fabrication and good flexibility.
An essential function of the inflammatory response is selective targeting of appropriate leukocyte types to a site of infection or injury. The past decade has witnessed an explosion in the level of ...detail concerning the identification and deciphering of the molecular mechanisms that capture leukocytes from flowing blood and promote leukocyte arrest on the vessel wall. In contrast, less information is known about the migration of adherent blood leukocytes through endothelial cell‐to‐cell borders (transendothelial migration, TEM) and into the underlying tissues. This article reviews the endothelial‐dependent mechanisms that coordinate TEM in peripheral vasculature and highlights the role of certain lateral junctional proteins and protein complexes.
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