32 research outputs found

    Flow cytometry immunophenotyping for diagnostic orientation and classification of pediatric cancer based on the euroflow solid tumor orientation tube (Stot)

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    © 2021 by the authors.Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination—solid tumor orientation tube, STOT—for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design–test–evaluate–redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/numyogenin/CD4-EpCAM/CD56/GD2/smCD3-CD19/cyCD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained. In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45− CD56++ non-hematopoietic solid tumors: 13/13 (GD2++ numyogenin− CD271−/+ nuMyoD1− CD99− EpCAM−) neuroblastoma samples, 5/5 (GD2− numyogenin++ CD271++ nuMyoD1++ CD99−/+ EpCAM−) rhabdomyosarcomas, 2/2 (GD2−/+ numyogenin− CD271+ nuMyoD1− CD99+ EpCAM−) Ewing sarcoma family of tumors, and 7/7 (GD2− numyogenin− CD271+ nuMyoD1− CD99− EpCAM+) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.This research was funded by the EuroFlow Consortium; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil (FAPERJ), numbers: E26/110.105/2014, E-26/010.101259/2018, and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, Brazil (CNPQ), Brasília, Brazil, numbers: 303765/2018-6, 409440/2016-7, and 400194/2014-7; and Instituto Desiderata/Chevron, Rio de Janeiro, Brazil, grant “Actions to improve pediatric cancer assistance in RJ”; the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15

    Flow cytometry immunophenotyping for diagnostic orientation and classification of pediatric cancer based on the EuroFlow Solid Tumor Orientation Tube (STOT)

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    Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination-solid tumor orientation tube, STOT-for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design-test-evaluate-redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/(nu)myogenin/CD4-EpCAM/CD56/GD2/(sm)CD3-CD19/(cy)CD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained.& nbsp;In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45(-) CD56(++) non-hematopoietic solid tumors: 13/13 (GD2(++) (nu)myogenin(-) CD271(-/+) (nu)MyoD1(-) CD99(-) EpCAM(-)) neuroblastoma samples, 5/5 (GD2(-) (nu)myogenin(++) CD271(++) (nu)MyoD1(++) CD99(-/+) EpCAM(-)) rhabdomyosarcomas, 2/2 (GD2(-/+) (nu)myogenin(-) CD271(+) (nu)MyoD1(-) CD99(+) EpCAM(-)) Ewing sarcoma family of tumors, and 7/7 (GD2(-) (nu)myogenin(-) CD271(+) (nu)MyoD1(-) CD99(-) EpCAM(+)) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

    A fast task-to-processor assignment heuristic for real-time multiprocessor DSP applications

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    The optimal assignment of the tasks to the processors to minimize total delay in a multiprocessor digital signal processing (DSP) architecture is extremely difficult, particularly for systems of many (e.g. 100) tasks. Two factors especially complicate the problem: (1) the multiprocessor architecture affects the inter-processor communication times, and (2) the specific assignment of tasks to processors affects the inter-task communication times. We develop a fast heuristic for assigning tasks to processors. There are two main ingredients in our method: (i) the choice of a useful general-purpose multiprocessor architecture for DSP applications, and (ii) an adaptive list-ordering heuristic which takes advantage of knowledge of the inter-processor communication characteristics of the chosen architecture. Examples are given, including comparisons to exact branch-and-bound methods, and a large sonar example. General digital signal processing system architectures consist of an arrangement of signal processing units connected by communication links. The task to be carried out by the signal processing units are specified via a task graph similar to a PERT diagram. The challenge is to assign the tasks in the task graph to the signal processing units in the architecture in an optimal manner. In this paper, we are interested in task-to-processor assignments that minimize the total delay, which is the lag between the first appearance of a signal at the input port and the production of a processed signal at the output port. The assignment process is complicated by need to consider the inter-task communication delays, which are themselves greatly affected by the assignment. The task-to-processor assignment problem is NP-complete, hence heuristics must be used. We develop a fast and effective heuristic for a specific general-purpose digital signal processing architecture
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