Optimal Multiuser Diversity in Multi-Cell MIMO Uplink Networks: User Scaling Law and Beamforming Design

We introduce a distributed protocol to achieve multiuser diversity in a multicell multiple-input multiple-output (MIMO) uplink network, referred to as a MIMO interfering multiple-access channel (IMAC). Assuming both no information exchange among base stations (BS) and local channel state information at the transmitters for the MIMO IMAC, we propose a joint beamforming and user scheduling protocol, and then show that the proposed protocol can achieve the optimal multiuser diversity gain, i.e., KM log (SNR log N), as long as the number of mobile stations (MSs) in a cell, N, scales faster than SNRKM-L/1-epsilon for a small constant epsilon > 0, where M, L, K, and SNR denote the number of receive antennas at each BS, the number of transmit antennas at each MS, the number of cells, and the signal-to-noise ratio, respectively. Our result indicates that multiuser diversity can be achieved in the presence of intra-cell and inter-cell interference even in a distributed fashion. As a result, vital information on how to design distributed algorithms in interference-limited cellular environments is provided

Tumor evolution and intratumor heterogeneity of an epithelial ovarian cancer investigated using next-generation sequencing

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background The extent to which metastatic tumors further evolve by accumulating additional mutations is unclear and has yet to be addressed extensively using next-generation sequencing of high-grade serous ovarian cancer. Methods Eleven spatially separated tumor samples from the primary tumor and associated metastatic sites and two normal samples were obtained from a Stage IIIC ovarian cancer patient during cytoreductive surgery prior to chemotherapy. Whole exome sequencing and copy number analysis were performed. Omental exomes were sequenced with a high depth of coverage to thoroughly explore the variants in metastatic lesions. Somatic mutations were further validated by ultra-deep targeted sequencing to sort out false positives and false negatives. Based on the somatic mutations and copy number variation profiles, a phylogenetic tree was generated to explore the evolutionary relationship among tumor samples. Results Only 6% of the somatic mutations were present in every sample of a given case with TP53 as the only known mutant gene consistently present in all samples. Two non-spatial clusters of primary tumors (cluster P1 and P2), and a cluster of metastatic regions (cluster M) were identified. The patterns of mutations indicate that cluster P1 and P2 diverged in the early phase of tumorigenesis, and that metastatic cluster M originated from the common ancestral clone of cluster P1 with few somatic mutations and copy number variations. Conclusions Although a high level of intratumor heterogeneity was evident in high-grade serous ovarian cancer, our results suggest that transcoelomic metastasis arises with little accumulation of somatic mutations and copy number alterations in this patient

Cation exchange chromatography removes FXIa from a 10% intravenous immunoglobulin preparation

The presence of residual activated coagulation factor XI (FXIa) in some commercial intravenous immunoglobulin (IVIG) products has been identified as the root cause of a small number of thromboembolic events in patients who had received such therapy. Our objectives here were to design and evaluate the manufacturing process of GC5107, a 10% glycine-stabilized IVIG product, for its capacity to remove FXIa. The manufacturing process included a cation exchange chromatography (CEX) step, which employs a resin that binds immunoglobulin G (IgG) with high capacity. Procoagulant activity was assessed using Western blot analysis, enzyme-linked immunosorbent assay, thrombin generation assay, chromogenic FXIa assay, and non-activated partial thromboplastin time (NaPTT) assay. A spiking study in which large quantities of FXIa were added to samples before CEX chromatography was used to examine the robustness of the process to remove FXIa. Western blot and ELISA analyses demonstrated that residual FXIa remained in the intermediate manufacturing products until after CEX chromatography, when it was reduced to undetectable levels. The spiking study demonstrated that CEX chromatography removed >99% of FXI protein and reduced FXI activity to below detection limits, even in samples containing 158-fold greater FXIa levels than that of normal samples. Procoagulant activity in 9 consecutive lots of GC5107 was reduced to below the detection limits of the thrombin generation and chromogenic FXIa assays (<1.56 IU/ml and <0.16 IU/ml, respectively). The NaPTT of >250 s in all 9 lots indicated very low levels of procoagulant activity. We demonstrate that a novel 10% IVIG manufacturing process including CEX chromatography is a robust means of removing FXIa from the final preparation

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma

Background BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients. Methods BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative. Results Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC. Conclusions Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC

Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease

Extramedullary multiple myeloma (EMD) is an aggressive subentity of multiple myeloma (MM) with poor progno‑ sis. As more innovative therapeutic approaches are needed for the treatment of MM with EMD, we conducted this multicenter, non-randomized phase II trial of daratumumab in combination with dexamethasone, cyclophospha‑ mide, etoposide and cisplatin (DARA-DCEP). A total of 32 patients (median age 59, range 35–73) were treated with DARA-DCEP. Based on the best response during the study, the complete remission (CR) rate was 35.5% and overall response rate (ORR) 67.7%. During the median follow-up of 11 months, the median progression-free survival (PFS) was 5 months and median overall survival (OS) 10 months. There were 7 long-term responders whose median PFS was not reached. The most common grade≥3 hematologic AE was thrombocytopenia. The most common non-hematologic AE was nausea (22.6%), followed by dyspepsia, diarrhea and stomatitis (all 12.9%). Grade≥3 daratumumab infusionrelated reaction was noted in 9.7% of the patients. Except for the planned 30% dose adjustment in cycle 1, only 2 patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we success‑ fully laid grounds for implementing immunochemotherapy in MM treatment.This work was supported by grants from the Korea Health Technolà ¢ ogy R&D Project through the Korea Health Industry Development Institute (KHIDI, HI14C1277)

Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia

PurposeImproved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.MethodsPatients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.ResultsFor random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.ConclusionFor a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity

Prostate Cancer with Solitary Metastases to the Bilateral Testis

We present the case of an 81-year-old patient with testicular metastasis from prostate carcinoma. After the initial diagnosis of prostate cancer, he had an 8-year course of hormonal therapy and showed no clinical evidence of metastasis to other organs. Asymptomatic metastasis of prostate carcinoma to the testis is a rare clinical condition. We diagnosed his condition, based on histopathology following a subcapsular orchiectomy and transurethral resection of the prostate