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Sample records for alk1-negative anaplastic large

  1. ALK-1-negative anaplastic large cell lymphoma associated with breast implants: a new clinical entity.

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    Lazzeri, Davide; Agostini, Tommaso; Bocci, Guido; Giannotti, Giordano; Fanelli, Giovanni; Naccarato, Antonio Giuseppe; Danesi, Romano; Tuccori, Marco; Pantaloni, Marcello; D'Aniello, Carlo

    2011-10-01

    Concerns have been raised recently regarding the increasing number of reports of non-Hodgkin lymphoma (NHL) that developed in close proximity to silicone or saline breast implants. In particular, an increased risk of anaplastic large cell lymphoma (ALCL) in patients with breast prostheses has been proposed. We reviewed clinical and pathologic findings in 40 women who received a diagnosis of breast NHL arising in association with breast implants and of 27 patients who had a diagnosis of ALCL with breast involvement reported in the published literature. Among the 40 reported cases of prosthesis-associated breast lymphomas, 28 were anaplastic lymphoma kinase-1-negative (ALK-1(-)) ALCLs, whereas of 27 ALCLs in patients without implants found in the literature, only 10 were ALK-1(-). The finding of 28 cases of breast ALK-1(-) ALCL occurring in patients with implants compared with 10 cases in women without implants is in favor of an association between silicone breast prostheses and ALK-1(-) ALCL. Although the incidence of this type of lymphoma remains remarkably low given that breast prostheses have been widely used for decades, clinical and pathologic evidence for a causative role is becoming dramatically strong. The histologic, phenomenologic, and clinical similarities of the majority of implant-related ALK-1(-) ALCLs suggest a common mechanism, especially when compared with the counterpart of patients without implants in which very few and highly dishomogeneous cases of the same malignancy were detected. There is convincing evidence that primary implant-related ALK-1(-) ALCL represents a distinct clinicopathologic entity that has been inappropriately fitted into the category of systemic ALK-1(-) ALCL. Thus it should be recognized as a separate category and classified on its own. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Fine needle aspiration cytology of ALK1(-), CD30+ anaplastic large cell lymphoma post renal transplantation: a case report and literature review.

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    Balachandran, Indra; Walker, Joe W; Broman, Jerry

    2010-03-01

    Post transplant lymphoproliferative disorders (PTLD) complicates the course of 0.3 to 3% of renal transplant patients receiving immunosuppression. Epstein-Barr virus (EBV) related non-Hodgkin's lymphomas of B-cell type is more common than those of T-cell origin. CD30 positive Anaplastic Large Cell Lymphoma (ALCL) is a Non-Hodgkin's lymphoma (B or T cell type) that accounts for a small percentage of PTLD's. ALCL of T-cell type are a spectrum of disease ranging from primary cutaneous to systemic nodal ALCL. The systemic nodal ALCL is further subdivided into anaplastic lymphoma kinase-1 (ALK-1) positive or negative. ALK-1 protein is a gene fusion product of translocation (2;5) and carries prognostic implications. We present an unusual manifestation of ALK-1 negative CD30 positive ALCL in a post renal transplant patient in FNA cytology with all supportive adjuvant studies and differential diagnoses and review the cytology literature on this topic.

  3. Primary cutaneous anaplastic large-cell lymphoma.

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    Perry, Edward; Karajgikar, Jay; Tabbara, Imad A

    2013-10-01

    Since the recognition of the anaplastic large-cell lymphomas in the 1980s, much has been learned about the diagnosis, clinical presentation, and treatment of these malignant conditions. The systemic and primary cutaneous types of anaplastic large cell lymphomas have been differentiated on clinical and immunophenotypical findings, but further research is required to elucidate their exact etiologies and pathogeneses. Primary cutaneous anaplastic large-cell lymphoma has a 95% disease-specific 5-year survival, owing partly to the relatively benign course of the disease and partly to the variety of effective treatments that are available. As with many other oncological diseases, new drugs are continually being tested and developed, with immunotherapy and biological response modifiers showing promise.

  4. Anaplastic large cell lymphoma of the breast arising around mammary implant capsule: an Italian report.

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    Farace, Francesco; Bulla, Antonio; Marongiu, Francesco; Campus, Gian Vittorio; Tanda, Francesco; Lissia, Amelia; Cossu, Antonio; Fozza, Claudio; Rubino, Corrado

    2013-06-01

    Anaplastic large cell lymphoma (ALCL) of the breast is a very rare nonepithelial neoplasm. In the literature, this tumor has sometimes been described in proximity of breast implants (60 implant-related ALCL reported). In 2010, a patient who had undergone a right mastectomy and tissue expander/implant reconstruction for a "ductal" carcinoma 10 years before was referred to our unit for evaluation. On examination, an enlarged reconstructed right breast was found. The reconstructed breast did not show tenderness or signs of infection, ulceration, or breakdown. Mammograms and ultrasound scan did not suggest the presence of recurrent cancer, infection, deflation of the implant, or severe capsule contracture. The patient underwent mammary implant replacement. About 3 weeks after surgery, the patient came back to our unit for a new mild enlargement of the operated breast and the implant was removed. Three months later, the patient returned with a skin lesion in the right parasternal region. A radical excisional biopsy was performed under local anesthesia and the diagnosis of ALK-1-negative ALCL was finally made. The clinical and histological diagnosis of this disease is difficult as it can often be mistaken for a simple seroma (breast enlargement), an infection, or an unspecific reaction to silicone (redness and/or tension of the skin, itching, and fever). We strongly suggest considering ALCL in any patient with a spontaneous breast seroma lasting more than 6 months after mammary prosthesis implantation. The suspicion of ALCL must be suggested to the pathologist immediately. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  5. Synchronous meningioma and anaplastic large cell lymphoma.

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    Colen, Chaim B; Rayes, Mahmoud; Kupsky, William J; Guthikonda, Murali

    2010-06-01

    Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

  6. Pathobiology of Anaplastic Large Cell Lymphoma

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    Pier Paolo Piccaluga

    2010-01-01

    Full Text Available The authors revise the concept of anaplastic large cell lymphoma (ALCL in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

  7. ALK Signaling and Target Therapy in Anaplastic Large Cell Lymphoma

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    Tabbó, Fabrizio; Barreca, Antonella; Piva, Roberto; Inghirami, Giorgio

    2012-01-01

    The discovery by Morris et al. (1994) of the genes contributing to the t(2;5)(p23;q35) translocation has laid the foundation for a molecular based recognition of anaplastic large cell lymphoma and highlighted the need for a further stratification of T-cell neoplasia. Likewise the detection of anaplastic lymphoma kinase (ALK) genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  8. [A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

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    Fujisawa, Etsuco; Shibayama, Hidehiro; Mitobe, Fumi; Katada, Fumiaki; Sato, Susumu; Fukutake, Toshio

    2017-11-25

    There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

  9. The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL

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    Ivonne A. Montes-Mojarro

    2018-04-01

    Full Text Available Anaplastic large cell lymphoma (ALCL represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO classification recognizes four different entities: systemic ALK-positive ALCL (ALK+ ALCL, systemic ALK-negative ALCL (ALK− ALCL, primary cutaneous ALCL (pC-ALCL, and breast implant-associated ALCL (BI-ALCL, the latter included as a provisional entity. ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly NPM1, and is associated with favorable prognosis, whereas systemic ALK− ALCL shows heterogeneous clinical, phenotypical, and genetic features, underlining the different oncogenesis between these two entities. Recognition of the pathological spectrum of ALCL is crucial to understand its pathogenesis and its boundaries with other entities. In this review, we will focus on the morphological, immunophenotypical, and molecular features of systemic ALK+ and ALK− ALCL. In addition, BI-ALCL will be discussed.

  10. ALK signaling and target therapy in anaplastic large cell lymphoma

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    Fabrizio eTabbo

    2012-05-01

    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  11. Anaplastic large cell lymphoma associated with breast implants

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    Vid Bajuk

    2017-02-01

    Full Text Available An increasing number of women worldwide decide for esthetic correction of breasts with silicone implants and post-cancer breast reconstruction with tissue expanders and silicone breast implants. It is estimated that more than 10 million women around the globe have them. Tere are approximately 200 known cases of patients with anaplastic large cell lymphoma (ALCL linked with silicone breast implants reported in medical literature. ALCL is a rare disease with an annual incidence of 0.1–0.3/100 000 women with breast silicone implants. In the presence of clinical signs, physician should also consider this rare form of ALCL in differential diagnosis. Patients are on average 50 years old. Long afer implantation surgery, the patient may experience breast swelling, pain and/or asymmetry. In diagnostics, ultrasound and cytological examination are required. During ultrasound examination fluid formation (seroma or solid tumor mass can be detected. Treatment is individualized. Due to tumor nature, implant resection and total capsulectomy are usually indicated; also, chemo- and radiotherapy might rarely be required. Five-year survival rate depends on tumor form and correlates well with clinical fndings of seroma or solid mass. In the more frequent form, seroma, fve-year survival rate is 100 %, while in the case of solid tumor mass fve-year survival rate is 75 %. The rarity of this disease makes it difficult to diagnose, but nevertheless, early detection and treatment are important for better recovery.

  12. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

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    Anupama Bains

    2016-01-01

    Full Text Available Primary cutaneous anaplastic large cell lymphoma (pcALCL forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary.

  13. Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual

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    Kumar Susheel

    2010-01-01

    Full Text Available Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL is a distinct type of non-Hodgkin′s lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

  14. ALK-positive anaplastic large cell lymphoma with soft tissue involvement in a young woman

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    Gao KH

    2016-07-01

    Full Text Available Kehai Gao, Hongtao Li, Caihong Huang, Huazhuang Li, Jun Fang, Chen Tian Department of Orthopaedics, Yidu Central Hospital, Shandong, People’s Republic of China Introduction: Anaplastic large cell lymphoma (ALCL is a type of non-Hodgkin lymphoma that has strong expression of CD30. ALCL can sometimes involve the bone marrow, and in advanced stages, it can produce destructive extranodal lesions. But anaplastic large cell lymphoma kinase (ALK+ ALCL with soft tissue involvement is very rare.Case report: A 35-year-old woman presented with waist pain for over 1 month. The biopsy of soft tissue lesions showed that these cells were positive for ALK-1, CD30, TIA-1, GranzymeB, CD4, CD8, and Ki67 (90%+ and negative for CD3, CD5, CD20, CD10, cytokeratin (CK, TdT, HMB-45, epithelial membrane antigen (EMA, and pan-CK, which identified ALCL. After six cycles of Hyper-CVAD/MA regimen, she achieved partial remission. Three months later, she died due to disease progression.Conclusion: This case illustrates the unusual presentation of ALCL in soft tissue with a bad response to chemotherapy. Because of the tendency for rapid progression, ALCL in young adults with extranodal lesions are often treated with high-grade chemotherapy, such as Hyper-CVAD/MA. Keywords: anaplastic large cell lymphoma, ALK+, soft tissue involvement, Hyper-CVAD/MA

  15. ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma

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    Rachel Hudacko

    2011-01-01

    Full Text Available Anaplastic lymphoma kinase protein (ALK-negative anaplastic large cell lymphoma (ALCL has a vast morphologic spectrum and may mimic many other types of malignancies both cytologically and histologically. There are only a few published case reports/series describing the cytomorphologic features of ALCL on fine-needle aspiration (FNA biopsy specimens. We describe a case of ALK-negative ALCL mimicking a high-grade soft tissue sarcoma of the thigh in a 62-year-old man. The characteristic morphologic findings on FNA and core biopsy along with the immunophenotypic profile are described and reviewed. The diagnosis of ALCL on FNA biopsy may be difficult, but can be done successfully with the use of ancillary tests. Therefore, it must be considered in the differential diagnosis of lesions with pleomorphism, anaplasia, and wreath-like or horseshoe-shaped nuclei to ensure that adequate material is obtained for ancillary studies.

  16. Primary cutaneous CD30+ anaplastic large-cell lymphoma in a young patient with psoriasis

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    Ming-Chun Chen

    2013-03-01

    Full Text Available Psoriasis is a common chronic inflammatory cutaneous disease, while primary cutaneous CD30+ anaplastic large-cell lymphoma (PC-ALCL is a rare T-cell lymphoma which always has an excellent prognosis, although multifocal PC-ALCL tends to relapse after systemic chemotherapy. Psoriasis associated with PC-ALCL is exceptionally rare. We report a 29-year-old Chinese female with a 5-year history of psoriasis treated with Chinese herbs alone, who was referred to our institution with a tumor on the left clavicular region for 1 year and another one on the left palm for 2 months. Skin biopsies of both lesions showed diffuse infiltration of tumor cells, composed of large atypical cells with marked nuclear pleomorphism, prominent nucleoli, and eosinophilic cytoplasm. Large numbers of neutrophilic infiltrations were also noted in the lesion. Immunostaining revealed the lesion to be positive for CD30, vimentin, CD45, and CD68, and weakly positive for epithelial membrane antigen, but negative for anaplastic lymphoma receptor tyrosine kinase. The patient was diagnosed to have psoriasis associated with PC-ALCL; she died 18 months after the final diagnosis with unknown cause. We consider that immune dysregulation and/or Chinese herbs may play roles in the development of the present PC-ALCL.

  17. Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

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    Jemima Sharp

    2012-01-01

    Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

  18. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

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    Chen X

    2013-12-01

    Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

  19. Anaplastic large cell lymphoma (ALCL) and breast implants: breaking down the evidence.

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    Ye, Xuan; Shokrollahi, Kayvan; Rozen, Warren M; Conyers, Rachel; Wright, Penny; Kenner, Lukas; Turner, Suzanne D; Whitaker, Iain S

    2014-01-01

    Systemic anaplastic large cell lymphoma (ALCL) is a distinct disease classification provisionally sub-divided into ALCL, Anaplastic Lymphoma Kinase (ALK)(+) and ALCL, ALK(-) entities. More recently, another category of ALCL has been increasingly reported in the literature and is associated with the presence of breast implants. A comprehensive review of the 71 reported cases of breast implant associated ALCL (iALCL) is presented indicating the apparent risk factors and main characteristics of this rare cancer. The average patient is 50 years of age and most cases present in the capsule surrounding the implant as part of the periprosthetic fluid or the capsule itself on average at 10 years post-surgery suggesting that iALCL is a late complication. The absolute risk is low ranging from 1:500,000 to 1:3,000,000 patients with breast implants per year. The majority of cases are ALK-negative, yet are associated with silicone-coated implants suggestive of the mechanism of tumorigenesis which is discussed in relation to chronic inflammation, immunogenicity of the implants and sub-clinical infection. In particular, capsulotomy alone seems to be sufficient for the treatment of many cases suggesting the implants provide the biological stimulus whereas others require further treatment including chemo- and radiotherapy although reported cases remain too low to recommend a therapeutic approach. However, CD30-based therapeutics might be a future option. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature

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    Eva Berlin

    2018-01-01

    Full Text Available We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging. The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

  1. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature.

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    Berlin, Eva; Singh, Kunwar; Mills, Christopher; Shapira, Ilan; Bakst, Richard L; Chadha, Manjeet

    2018-01-01

    We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging). The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

  2. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

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    Vibhu Mendiratta

    2016-01-01

    Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

  3. High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma

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    Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

    2014-01-01

    AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pre......-therapeutic parameters and outcome in a cohort of treatment-naive ALCL patients. METHODS AND RESULTS: Pre-therapeutic tumour specimens from 52 patients with ALCL were included in a tissue microarray. The intratumoral macrophage content was assessed by immunohistochemical staining for CD68 and CD163, and quantified using......-free survival in ALK-negative patients (P macrophages correlates with an adverse outcome in ALK-negative ALCL....

  4. Primary Cutaneous CD 30+ Anaplastic Large Cell Lymphoma. A Case Report and Literature Review

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    Miguel Ángel Serra Valdés

    2014-03-01

    Full Text Available Primary cutaneous CD 30+ anaplastic large cell lymphoma is part of the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, together with lymphomatoid papulosis. Its frequency is less than 0.5 x 100 000 inhabitants per year. It accounts for a very small proportion of non-Hodgkins lymphomas. The case of an 80-year-old female patient whose diagnosis was established in 2006 because of lesions on the face and neck is presented. The lesions continued to grow in an exaggerated fashion lately leading to deformity of her face. She was admitted due to neurological manifestations unrelated to the lesions. The presentation of this case is necessary because it requires performing differential diagnosis in clinical practice. Given its rarity, it is of interest to the medical community, especially trainees.

  5. Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL: Current Standard and beyond

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    Nina Prokoph

    2018-03-01

    Full Text Available Anaplastic Lymphoma Kinase (ALK-positive Anaplastic Large Cell Lymphoma (ALCL, remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65–90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and ‘renewed’ agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and ‘renewed’ agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials.

  6. Breast implants and anaplastic large-cell lymphoma: a danish population-based cohort study.

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    Vase, Maja Ølholm; Friis, Søren; Bautz, Andrea; Bendix, Knud; Sørensen, Henrik Toft; d'Amore, Francesco

    2013-11-01

    A potential link between breast implants and anaplastic large-cell lymphoma (ALCL) has been suggested. We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973-2010. Standardized incidence ratios (SIR), with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated. During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs for ALCL and lymphoma overall were zero (95% CI, 0-10.3) and 1.20 (95% CI, 0.82-1.70), respectively. In our nationwide cohort study, we did not find an increased risk of lymphoma in general, or ALCL in particular, among Danish women who underwent breast implantation. However, our evaluation of ALCL risk was limited by the rarity of the disease. Our results do not support an association between breast implants and ALCL and are consistent with other studies on cancer risk and breast implants. ©2013 AACR.

  7. Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

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    Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

    2014-04-01

    Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

  8. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Margarita Baka

    2013-01-01

    Full Text Available A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL, whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months, pyrazinamide (the first 2 months, and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

  9. Treatment of primary cutaneous anaplastic large cell lymphoma with superficial x-rays

    DEFF Research Database (Denmark)

    Jepsen, Malene E; Gniadecki, Robert

    2015-01-01

    The optimal radiation schedule for primary cutaneous anaplastic lymphoma (PCALCL) has not been investigated. We report here satisfactory outcomes of low-dose (16-20 Gy, 3-5 fractions), superficial X-ray radiation (40-50 kV) in a series of 10 patients with PCALCL. Only 1 patient developed a local...

  10. Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

    Hu, Honghua; Johani, Khalid; Almatroudi, Ahmad; Vickery, Karen; Van Natta, Bruce; Kadin, Marshall E; Brody, Garry; Clemens, Mark; Cheah, Chan Yoon; Lade, Stephen; Joshi, Preeti Avinash; Prince, H Miles; Deva, Anand K

    2016-06-01

    A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant-associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Twenty-six breast implant-associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Both the breast implant-associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant-associated ALCL, 4.7 × 10 cells/mg of tissue; capsule, 4.9 × 10 cells/mg of tissue). Analysis of the microbiome in breast implant-associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p capsule specimens compared with breast implant-associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. This novel finding of bacterial biofilm and a distinct microbiome in breast implant-associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. Risk, V.

  11. Prognostic significance and therapeutic potential of the activation of anaplastic lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway in anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Gao, Ju; Yin, Minzhi; Zhu, Yiping; Gu, Ling; Zhang, Yanle; Li, Qiang; Jia, Cangsong; Ma, Zhigui

    2013-01-01

    Activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of other cancers. However, the prognostic value of AKT/mTOR activation in ALCL remains to be fully elucidated. In the present study, we aim to address this question from a clinical perspective by comparing the expressions of the AKT/mTOR signaling molecules in ALCL patients and exploring the therapeutic significance of targeting the AKT/mTOR pathway in ALCL. A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATK/mTOR signaling pathway were further investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK transformed BaF3 cells. ALK expression was detected in 60% of ALCLs, of which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT) and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred more commonly in younger patients, and ALK + ALCL patients had a much better prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM-ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the

  12. Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

    Energy Technology Data Exchange (ETDEWEB)

    Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

    2016-08-01

    Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

  13. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report.

    Science.gov (United States)

    Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

    2006-10-19

    Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

  14. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

    Directory of Open Access Journals (Sweden)

    Dehghani Mehdi

    2006-01-01

    Full Text Available Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

  15. Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation: A case report of a rare tumor

    Directory of Open Access Journals (Sweden)

    Amany A. Fathaddin

    2014-01-01

    Full Text Available Medulloblastoma is an embryonal neuroepithelial tumor of the cerebellum and is the most common malignant central nervous system tumor in children. Different histological variants and patterns have been described. The classic variant represents the majority of cases. This report describes a rare case of large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation arising in the cerebellum of a 3-year-old boy who presented with headache and vomiting. Magnetic resonance imaging demonstrated a heterogeneously enhanced lesion in the fourth ventricle. Surgical resection of the tumor was accomplished, but a residual tumor was left behind because of the involvement of the brainstem. Postoperatively, the patient received chemotherapy and radiotherapy. Currently, 20 months after treatment, the patient has survived without further progression. Pathological examination revealed a high grade primitive neuronal tumor with foci of myogenic features, melanin containing epithelial elements and ganglion-like cells, which were confirmed by immunohistochemistry.

  16. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

    Science.gov (United States)

    Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

    2012-02-01

    Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

  17. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  18. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

    Science.gov (United States)

    Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-01-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

  19. Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling

    Directory of Open Access Journals (Sweden)

    Melanie R. Hassler

    2016-10-01

    Full Text Available Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+ and NPM-ALK-negative (ALK− anaplastic large-cell lymphoma (ALCL. We find that ALK+ and ALK− ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.

  20. The non-specific symptoms of breast implant-associated anaplastic large cell lymphoma resulting in delayed diagnosis: A case-based review

    Directory of Open Access Journals (Sweden)

    Reem Dina Jarjis

    2015-12-01

    Full Text Available Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL is a rare entity that has become known as a distinct clinical condition recently. In general, BIA-ALCL patients with a history of breast implants present with non-specific implant-related complications, resulting in delayed diagnosis and appropriate treatment because of the lack of awareness of BIA-ALCL. The cause and pathogenesis have still not been identified, and there are no evidence-based guidelines on how this condition should be detected, treated or followed up because of the rarity of available data. We present the first published Danish case of anaplastic lymphoma kinase negative BIA-ALCL, and review the current literature to raise awareness of and discuss management options for this rare clinical entity.

  1. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

    Science.gov (United States)

    Miranda, Roberto N.; Aladily, Tariq N.; Prince, H. Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E.; Amin, Mitual B.; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S.; Shifrin, David A.; O'Malley, Dennis P.; Cheah, Chan Y.; Bacchi, Carlos E.; Gualco, Gabriela; Li, Shiyong; Keech, John A.; Hochberg, Ephram P.; Carty, Matthew J.; Hanson, Summer E.; Mustafa, Eid; Sanchez, Steven; Manning, John T.; Xu-Monette, Zijun Y.; Miranda, Alonso R.; Fox, Patricia; Bassett, Roland L.; Castillo, Jorge J.; Beltran, Brady E.; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H.; Medeiros, L. Jeffrey

    2014-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. PMID:24323027

  2. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients.

    Science.gov (United States)

    Miranda, Roberto N; Aladily, Tariq N; Prince, H Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E; Amin, Mitual B; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S; Shifrin, David A; O'Malley, Dennis P; Cheah, Chan Y; Bacchi, Carlos E; Gualco, Gabriela; Li, Shiyong; Keech, John A; Hochberg, Ephram P; Carty, Matthew J; Hanson, Summer E; Mustafa, Eid; Sanchez, Steven; Manning, John T; Xu-Monette, Zijun Y; Miranda, Alonso R; Fox, Patricia; Bassett, Roland L; Castillo, Jorge J; Beltran, Brady E; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H; Medeiros, L Jeffrey

    2014-01-10

    Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

  3. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

    Clemens, Mark W; Medeiros, L Jeffrey; Butler, Charles E; Hunt, Kelly K; Fanale, Michelle A; Horwitz, Steven; Weisenburger, Dennis D; Liu, Jun; Morgan, Elizabeth A; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R; Ferry, Judith A; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; DiNapoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M; Hanson, Summer E; Nastoupil, Loretta J; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H; Miranda, Roberto N

    2016-01-10

    Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. © 2015 by American Society of Clinical Oncology.

  4. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

    Science.gov (United States)

    Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.

    2016-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

  5. Anaplastic thyroid cancer

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

  6. Anaplastic Large Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  7. [A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

    Science.gov (United States)

    Gorgidze, L A; Vorob'ev, I A

    2009-01-01

    To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

  8. Change in the diagnosis from classical Hodgkin's lymphoma to anaplastic large cell lymphoma by 18F flourodeoxyglucose positron emission tomography/computed tomography: Importance of recognising disease pattern on imaging and immunohistochemistry

    International Nuclear Information System (INIS)

    Senthil, Raja; Mohapatra, Ranjan Kumar; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare type of nonHodgkin's lymphoma (NHL), but one of the most common subtypes of T-cell lymphoma. It is an aggressive T-cell lymphoma, and some ALCL may mimic less aggressive classical HL histopathlogically. It may be misdiagnosed unless careful immunohistochemical examination is performed. As the prognosis and management of these two lymphomas vary significantly, it is important to make a correct diagnosis. We describe a case who was diagnosed as classical HL by histopathological examination of cervical lymph node, in whom 18 F-flouro deoxyglucose positron emission tomography/computed tomography appearances were unusual for HL and warranted review of histopathology that revealed anaplastic lymphoma kinase-1 negative anaplastic large T-cell lymphoma, Hodgkin-like variant, thereby changing the management

  9. Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

    Science.gov (United States)

    Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M

    2015-11-01

    Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Anaplastic pleomorphic xanthoastrocytoma

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    Li-wei SHAO

    2017-09-01

    Full Text Available Objective To investigate the clinicopathological features, immune phenotype and gene mutation characteristics, and diagnosis or differential diagnosis of anaplastic pleomorphic xanthoastrocytoma (PXA. Methods and Results A 11 - year- old male patient presented with more than half month of headache, and left upper limb weakness. Cranial CT and MRI revealed a large space-occupying lesion in the right parietal lobe and basal ganglia which was suggested as glioma. During operation the tumor was examined. It was a cystic-solid lesion. The solid part was soft and greyish yellow with rich blood supply and without membrane, and the boundary was clear. Intraoperative freezing pathologic examination showed the tumor was a low grade glioma. The right parietal glioma was completely removed piece by piece under the microscopy. Histologically, the tumor cells were polymorphism, including spindle or round astrocytes, monocytes and multinuclear tumor giant cells. Mitoses were rarely seen. Differentiation of mature neuronal cells or ganglion cells with lymphocyte infiltration were seen in focal region. In some regions, tumor cells were anaplastic, and cellularity were increased. Atypical round or spindle cells were seen, and atypical mitoses > 5/10 high power field (HPF were found. icrovascular proliferation, perivascular pseudorosettes and localized necrosis were also evident. Immunohistochemically, tumor cells were positive for glial fibrillary acidic protein (GFAP, BRAF V600E, S-100 protein (S-100, CD34, synaptophysin (Syn, non- phosphorylation neurofilament heauy chain SMI- 32 and P53, but negative for isocitrate dehydrogenase 1(IDH1, neurofilament protein (NF and epithelial membrane antigen (EMA. Ki - 67 labeling index was about 3% in low grade tumor cells, while Ki-67 labeling index was about 30% in high grade tumor cells. In reticular fibre tissue staining, a lot of reticular fibre tissue were seen. BRAF V600E heterozygous mutation c.1799A > T was

  11. TARC, a CC chemokine, is frequently expressed in classic Hodgkin's lymphoma but not in NLP Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and most cases of anaplastic large cell lymphoma

    NARCIS (Netherlands)

    Peh, SC; Kim, LH; Poppema, S

    Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large

  12. The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

    Science.gov (United States)

    Georgakis, Georgios V; Li, Yang; Rassidakis, Georgios Z; Medeiros, L Jeffrey; Younes, Anas

    2006-12-01

    Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

  13. An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

    Science.gov (United States)

    Lollies, A; Hartmann, S; Schneider, M; Bracht, T; Weiß, A L; Arnolds, J; Klein-Hitpass, L; Sitek, B; Hansmann, M-L; Küppers, R; Weniger, M A

    2018-01-01

    Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30 + lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30 + diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

  14. Gingival Anaplastic Large-Cell Lymphoma Mimicking Hyperplastic Benignancy as the First Clinical Manifestation of AIDS: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Rafaela Elvira Rozza-de-Menezes

    2013-01-01

    Full Text Available This paper presents an unusual case of gingival ALCL, which mimicked a benign hyperplastic lesion that occurred in a 57-year-old white man representing the first clinical manifestation of acquired immunodeficiency syndrome (AIDS. The patient was referred to the Dental Clinic of PUCPR complaining of a lobulated nodule on the gingiva of his upper central incisors. The presence of advanced chronic periodontitis and dental plaque raised suspicion for a benignancy. An excisional biopsy was performed, and large pleomorphic cells with an abundant cytoplasm, sometimes containing prominent nucleoli and “Hallmark” cells, were observed through hematoxylin and eosin staining. The tumor cells showed strong CD30 expression, EMA, Ki-67, and LCA, and negative stain for p80NPM/ALK, CKAE1/AE3, CD20, CD3, CD56, and CD15. The final diagnosis was ALCL (ALK-negative. Further laboratory tests revealed positivity for human immunodeficiency virus (HIV. The patient was submitted to chemotherapy, but four months after diagnosis, the patient died due to pneumonia and respiratory failure. Oral anaplastic large-cell lymphoma (ALCL is a rare disorder. Only 5 cases involving the gingiva have been reported, and to our knowledge, this is the first case reported of the ALCL, which mimicked a hyperplastic benignancy as the first clinical manifestation of AIDS.

  15. EMMPRIN (CD147) is induced by C/EBPβ and is differentially expressed in ALK+ and ALK- anaplastic large-cell lymphoma.

    Science.gov (United States)

    Schmidt, Janine; Bonzheim, Irina; Steinhilber, Julia; Montes-Mojarro, Ivonne A; Ortiz-Hidalgo, Carlos; Klapper, Wolfram; Fend, Falko; Quintanilla-Martínez, Leticia

    2017-09-01

    Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro. To analyze the role of C/EBPβ for the unusual phenotype of ALK+ ALCL cells, C/EBPβ was knocked down by RNA interference in two ALK+ ALCL cell lines, and surface antigen expression profiles of these cell lines were generated using a Human Cell Surface Marker Screening Panel (BD Biosciences). Interesting candidate antigens were further analyzed by immunohistochemistry in primary ALCL ALK+ and ALK- cases. Antigen expression profiling revealed marked changes in the expression of the activation markers CD25, CD30, CD98, CD147, and CD227 after C/EBPβ knockdown. Immunohistochemical analysis confirmed a strong, membranous CD147 (EMMPRIN) expression in ALK+ ALCL cases. In contrast, ALK- ALCL cases showed a weaker CD147 expression. CD274 or PD-L1, an immune inhibitory receptor ligand, was downregulated after C/EBPβ knockdown. PD-L1 also showed stronger expression in ALK+ ALCL compared with ALK- ALCL, suggesting an additional role of C/EBPβ in ALK+ ALCL in generating an immunosuppressive environment. Finally, no expression changes of T-cell or monocytic markers were detected. In conclusion, surface antigen expression profiling demonstrates that C/EBPβ plays a critical role in the activation state of ALK+ ALCL cells and reveals CD147 and PD-L1 as important downstream targets. The multiple roles of CD147 in migration, adhesion, and invasion, as well as

  16. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

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    Rocco Piazza

    2013-05-01

    Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  17. The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.

    Science.gov (United States)

    Unger, Christine; Popescu, Ruxandra; Giessrigl, Benedikt; Laimer, Daniela; Heider, Susanne; Seelinger, Mareike; Diaz, Rene; Wallnöfer, Bruno; Egger, Gerda; Hassler, Melanie; Knöfler, Martin; Saleh, Leila; Sahin, Emine; Grusch, Michael; Fritzer-Szekeres, Monika; Dolznig, Helmut; Frisch, Richard; Kenner, Lukas; Kopp, Brigitte; Krupitza, Georg

    2013-01-01

    The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted.

  18. Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

    Science.gov (United States)

    J Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

    2018-06-01

    Patients treated with intravesical bacillus Calmette-Guérin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side-effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation.

    Science.gov (United States)

    Kiss, Izabella; Unger, Christine; Huu, Chi Nguyen; Atanasov, Atanas Georgiev; Kramer, Nina; Chatruphonprasert, Waranya; Brenner, Stefan; McKinnon, Ruxandra; Peschel, Andrea; Vasas, Andrea; Lajter, Ildiko; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

    2015-01-28

    An apolar extract of the traditional medicinal plant Neurolaena lobata inhibited the expression of the NPM/ALK chimera, which is causal for the majority of anaplastic large cell lymphomas (ALCLs). Therefore, an active principle of the extract, the furanoheliangolide sesquiterpene lactone lobatin B, was isolated and tested regarding the inhibition of ALCL expansion and tumour cell intravasation through the lymphendothelium. ALCL cell lines, HL-60 cells and PBMCs were treated with plant compounds and the ALK inhibitor TAE-684 to measure mitochondrial activity, proliferation and cell cycle progression and to correlate the results with protein- and mRNA-expression of selected gene products. Several endpoints indicative for cell death were analysed after lobatin B treatment. Tumour cell intravasation through lymphendothelial monolayers was measured and potential causal mechanisms were investigated analysing NF-κB- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-Rβ, and attenuated proliferation of ALCL cells by arresting them in late M phase. Mitochondrial activity remained largely unaffected upon lobatin B treatment. Nevertheless, caspase 3 became activated in ALCL cells. Also HL-60 cell proliferation was attenuated whereas PBMCs of healthy donors were not affected by lobatin B. Additionally, tumour cell intravasation, which partly depends on NF-κB, was significantly suppressed by lobatin B most likely due to its NF-κB-inhibitory property. Lobatin B, which was isolated from a plant used in ethnomedicine, targets malignant cells by at least two properties: I) inhibition of NPM/ALK, thereby providing high specificity in combating this most prevalent fusion protein occurring in ALCL; II) inhibition of NF-κB, thereby not affecting normal cells with low constitutive NF-κB activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this

  20. Is Latin America Ready to Identify Anaplastic Large Cell Lymphoma in Breast Implants Patients? Regional Encounter During the National Plastic Surgery Meeting in Cancun, Mexico.

    Science.gov (United States)

    Ramos-Gallardo, Guillermo; Cuenca-Pardo, Jesus; Cardenas-Camarena, Lazaro; Duran-Vega, Hector; Rodríguez-Olivares, Eugenio; Bayter-Marin, Jorge Enrique; Levelier De Doig Alvear, Gerardo; Vazquez, Guillermo; Fontbona-Torres, Montserrat; Galán-Suárez, Ricardo; Guzman-Stein, Gabriela; Guzmán-Padilla, Sergio; Echeverría-Roldán, Guillermo; Silva-Gavarrete, Jose Fernando; Vallarta-Rodríguez, Alfonso; Contreras-Bulnes, Livia; Oaxaca-Escobar, Carlos Guillemro; Caravantes-Cortes, Isabel; Flores, María Eugenia; Cowes-McGowen, Jorge; Maciel-Sosa, María Liz; Delgado-Binasco, Ricardo; Rincón-Rubio, Linda

    2018-05-16

    Anaplastic large cell lymphoma associated with breast implants is receiving increased attention. Most cases have been reported in Europe, North America (USA and Canada), Australia and New Zealand. Fewer cases have been reported in Latin America (including Mexico), Africa and Asia. This report was delivered during our national plastic surgery meeting in Cancun in May 2017. Before the meeting, two participants reviewed the literature. The review was performed using the following information sources: PubMed, Embase, Cochrane, Fisterra, Google Scholar and LILACS, with entries from 1980 to August 2015 in several languages (English, Spanish, French and Portuguese). The results were revealed during the meeting to the other participants. The consensus was divided into two parts. The first part included an open-ended question regarding the incidence and prevalence of the problem. The second part included clinical scenarios with different items that were rated by the participants. After this activity, accordance among the responses was evaluated. Seven cases were reported during the meeting (3 from Mexico, 3 from Chile and 1 from Argentina). Fifty percent of the participants reported consulting with guidelines and clinical centers to help with potential cases. Most agreed that further studies must be done in cases of chronic seroma where the capsule plays an important role. A current debate exists about the incidence of this problem in Latin America because we did not report the same number of cases as Europe, Australia or North America. More studies are required to determine the differences among reports in Latin America. Most representatives agreed that further studies must be done. Concern is increasing, and the problem is known. Other factors involved may be considered, and the problem must not be ignored. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the

  1. Silicone-induced granuloma of breast implant capsule (SIGBIC: similarities and differences with anaplastic large cell lymphoma (ALCL and their differential diagnosis

    Directory of Open Access Journals (Sweden)

    Fleury EF

    2017-03-01

    Full Text Available Eduardo de Faria Castro Fleury,1 Milena Morais Rêgo,1 Luciana Costa Ramalho,1 Veronica Jorge Ayres,1 Rodrigo Oliveira Seleti,2 Carlos Alberto Pecci Ferreira,2 Decio Roveda Jr 2 1Radiology Department, IBCC – Instituto Brasileiro de Controle do Câncer, 2Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil Abstract: Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease. Keywords: lymphoma, granuloma, breast cancer, implant

  2. Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation

    Directory of Open Access Journals (Sweden)

    Sur Monalisa

    2009-04-01

    Full Text Available Abstract Background Primary non-Hodgkin lymphoma (NHL of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML, the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude

  3. The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein

    International Nuclear Information System (INIS)

    Pearson, Joel D; Mohammed, Zubair; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J

    2012-01-01

    Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK) with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90) plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40), is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines. NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP) 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined. We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to be due to a decrease in NPM-ALK levels or the

  4. Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

    Science.gov (United States)

    Salama, S

    2005-06-01

    Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

  5. Classical and anaplastic seminoma: Difference in survival

    International Nuclear Information System (INIS)

    Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

    1987-01-01

    The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

  6. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

  7. Leptomeningeal metastases from anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Solomon, B.; Rischin, D.; Lyons, B.; Peters, L.J.

    2000-01-01

    Anaplastic thyroid carcinoma is an extremely aggressive neoplasm that accounts for 1-3% of all thyroid cancers. ' Most patients have metastatic disease at presentation and die in a short period of time, often with uncontrolled local disease. We report a case of anaplastic thyroid cancer characterised by good response to initial treatment both locally and in distant metastases, and the subsequent development of refractory metastatic disease in an unusual site, the leptomeninges

  8. Postoperative radiotherapy of supratentorial anaplastic gliomas

    International Nuclear Information System (INIS)

    Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

    1986-01-01

    Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

  9. Pleomorphic xanthoastrocytoma with anaplastic features

    Directory of Open Access Journals (Sweden)

    Cheng ZHI

    2015-08-01

    Full Text Available Objective  To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA with anaplastic features.  Methods  HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP, vimentin (Vim, CD34, epithelial membrane antigen (EMA, progestrone receptor (PR, neurofilment protein (NF, neuronal nuclei (NeuN, synaptophysin (Syn, Nestin (Nes, S-100 protein (S-100, P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR amplification.  Results  A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and "map"-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found.  Conclusions  Classified as grade Ⅱ in the World Health Organization (WHO classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF and/or areas of

  10. Cerebral oligodendroglioma: MR features indicating anaplastic changes

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    Choi, Choong Gon; Chang, Kee Hyun; Han, Moon Hee; Chi, Je Geun [Seoul National Univ., Seoul (Korea, Republic of); Yoon, Hyun Ki [Ulsan Univ., Seoul (Korea, Republic of)

    1995-10-15

    The purpose of this study is to find helpful MR findings for predicting anaplastic oligodendrogliomas. Retrospective analysis of 46 MR images and 37 CT scans was performed for 46 patients with pathologically-proven cerebral oligodendrogliomas. A neuropathologist graded the tumors as one of low-grade (n = 16), intermediate-grade (n = 12), or anaplastic oligodendroglioma (n 18). MR imaging features were retrospectively analysed with respect to histologic grading of the tumors. Contrast enhancement was observed always in anaplastic group (17/17), in a portion of intermediate-grade group (4/10) but not in low-grade group (0/4). Peritumoral edema was observed infrequently in anaplastic group (4/18) or intermediate-grade group (1/12). Cystic changes (25/46) or calcifications on CT Scans (14/37) were not related with histologic grading. Grossly identifiable hemorrhage was rare in this series (2/46). Among the various imaging features, only tumor enhancement and peritumoral edema were statistically significant for trend test ({rho} < 0.05). When considering the diagnosis of oligodendrogliomas, the presence of contrast enhancement or peritumoral edema is a helpful features suggesting anaplastic oligodendrogliomas.

  11. Anaplastic meningioma: The dark side of meningiomas

    Directory of Open Access Journals (Sweden)

    Andreea Cioca

    2017-06-01

    Full Text Available Anaplastic meningioma is a rare malignant tumor of the meninges, with a very aggressive behavior and a grim prognosis. Here we report a case of a 64-year old man which presented to the neurosurgery department with motor deficit in the right hemi–body, loss of speech and disorientation. Magnetic resonance imaging detected a mass located in the left frontal lobe that measured 7/8/7 cm, leading to the conclusion that surgery is necessary. Microscopic examination of the tumor showed great number of hypercellular areas with a high mitotic index, and focal necrosis with psammoma bodies. Using a panel of antibodies such as EMA, vimentin, CD34 GFAP, pancytokeratin and Ki67, we concluded that he final diagnosis was anaplastic meningioma, WHO grade III. Due to its morphological similarity with other tumors, the diagnosis of anaplastic meningioma may be challenging.

  12. Anaplastic Carcinoma and Toxic Multinodular Goiter: An Unusual Presentation

    Science.gov (United States)

    Marcelino, Mafalda; Marques, Pedro; Lopes, Luis; Leite, Valeriano; de Castro, João Jácome

    2014-01-01

    A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far. PMID:25759806

  13. CT imaging features of anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Shi Zhenshan; You Ruixiong; Cao Dairong; Li Yueming; Zhuang Qian

    2013-01-01

    Objective: To investigate the CT characteristics of anaplastic thyroid carcinoma and evaluate the diagnostic value of CT in this disease. Methods: The CT findings of 10 patients with pathologically proved anaplastic thyroid carcinoma were retrospectively reviewed. The patients included 7 females and 3 males. Their age ranged from 25.0 to 78 years with median of 61 years. Multi-slices plain and post contrast CT scans were performed in all patients. Results: Unilateral thyroid was involved in 6 patients. Unilateral thyroid and thyroid isthmus were both involved in 2 patients due to big size. Bilateral thyroid were involved in 2 patients. The maximum diameter of anaplastic thyroid carcinoma ranged from 2.9-12.8 cm with mean of (4.5 ± 1.4) cm. All lesions demonstrated unclear margins and envelope invasion. The densities of all lesions were heterogeneous and obvious necrosis areas were noted on precontrast images. Seven lesions showed varied calcifications, and coarse granular calcifications were found in 5 lesions among them. All lesions showed remarkable heterogenous enhancement on post-contrast CT. The CT value of solid portion of the tumor increased 40 HU after contrast media administration. The ratios of CT value which comparing of the tumor with contralateral sternocleidomastoid muscle were 0.69-0.82 (0.76 ± 0.18) and 1.25-1.41 (1.33 ± 0.28) on pre and post CT, respectively. Enlarged cervical lymph nodes were found in 6 cases (60.0%). It showed obvious homogeneous enhancement or irregular ring-like enhancement on post-contrast images and dot calcifications were seen in 1 case. Conclusions: Relative larger single thyroid masses with coarse granular calcifications, necrosis,envelope invasion, remarkable heterogeneous enhancing and enlarged lymph nodes on CT are suggestive of anaplastic thyroid carcinoma. (authors)

  14. The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

    Science.gov (United States)

    Gravanis, Iordanis; Tzogani, Kyriaki; van Hennik, Paula; de Graeff, Pieter; Schmitt, Petra; Mueller-Berghaus, Jan; Salmonson, Tomas; Gisselbrecht, Christian; Laane, Edward; Bergmann, Lothar; Pignatti, Francesco

    2016-01-01

    On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option. Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody (recombinant chimeric IgG1) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE). Binding of the ADC to CD30 on the cell surface initiates internalization of the MMAE-CD30 complex, followed by proteolytic cleavage that releases MMAE. The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Brentuximab vedotin as a single agent was evaluated in two single-arm studies. Study SG035-003 included 102 patients with relapsed or refractory HL. An objective response was observed in 76 patients (75%), with complete remission in 34 (33%). Study SG035-004 included 58 patients with relapsed or refractory sALCL. An objective response was observed in 50 patients (86%), with complete remission in 34 (59%). The most frequently observed toxicities were peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, vomiting, pyrexia, and upper respiratory tract infection. The present report summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of the product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu). Brentuximab vedotin was approved in the European Union for the treatment of adult

  15. Suprasellar Anaplastic Meningioma Masquerading As Craniopharyngioma: A Case Report

    Directory of Open Access Journals (Sweden)

    Eman Abdelzaher

    2014-06-01

    Full Text Available Anaplastic meningiomas are uncommon. We report the clinical, radiological and pathological features of an anaplastic meningioma in a young male Egyptian patient presenting as a suprasellar solid/cystic enhancing mass resembling a craniopharyngioma. [J Interdiscipl Histopathol 2014; 2(3.000: 154-157

  16. Anaplastic myxopapillary ependymoma in an infant: Case report and literature review.

    Science.gov (United States)

    Trivedi, Darshan; Xiong, Zhenggang

    2017-05-01

    A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyperplasia. These findings were consistent with an anaplastic myxopapillary ependymoma. Subtotal resection was performed via a T3-T10 laminoplasty. A ventricular shunt was placed, and the patient subsequently received chemoradiation therapy. To date, this is the second case of a myxopapillary ependymoma with high-grade anaplastic features and the first case in an infant reported in the literature.

  17. Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma.

    Science.gov (United States)

    Wiestler, Benedikt; Capper, David; Sill, Martin; Jones, David T W; Hovestadt, Volker; Sturm, Dominik; Koelsche, Christian; Bertoni, Anna; Schweizer, Leonille; Korshunov, Andrey; Weiß, Elisa K; Schliesser, Maximilian G; Radbruch, Alexander; Herold-Mende, Christel; Roth, Patrick; Unterberg, Andreas; Hartmann, Christian; Pietsch, Torsten; Reifenberger, Guido; Lichter, Peter; Radlwimmer, Bernhard; Platten, Michael; Pfister, Stefan M; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang

    2014-10-01

    The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.

  18. Remarkable Presentation: Anaplastic Thyroid Carcinoma Arising from Chronic Hyperthyroidism

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    Habib G. Zalzal

    2018-01-01

    Full Text Available Background. Undifferentiated anaplastic carcinoma rarely develops from chronic hyperthyroidism. Although acute hyperthyroidism can develop prior to anaplastic transformation, chronic hyperthyroidism was thought to be a protective measure against thyroid malignancy. Methods. A 79-year-old female presented acutely to the hospital with dyspnea. She had been taking methimazole for chronic hyperthyroidism due to toxic thyroid nodules, previously biopsied as benign. Upon admission, imaging showed tracheal compression, requiring a total thyroidectomy with tracheostomy for airway management. Results. Pathology demonstrated undifferentiated anaplastic thyroid carcinoma. The patient passed away shortly after hospital discharge. Despite treatment with methimazole for many years, abrupt enlargement of her toxic multinodular goiter was consistent with malignant transformation. Chronic hyperthyroidism and toxic nodules are rarely associated with thyroid malignancy, with only one previous report documenting association with anaplastic thyroid carcinoma. Conclusion. Progressive thyroid enlargement and acute worsening of previously controlled hyperthyroidism should promote concern for disease regardless of baseline thyroid function.

  19. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma.

    Science.gov (United States)

    Coco, Simona; De Mariano, Marilena; Valdora, Francesca; Servidei, Tiziana; Ridola, Vita; Andolfo, Immacolata; Oberthuer, André; Tonini, Gian Paolo; Longo, Luca

    2012-10-01

    The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.

  20. Meningioma anaplásico Anaplastic meningioma

    Directory of Open Access Journals (Sweden)

    Arlines Alina Piña Tornés

    2013-03-01

    Full Text Available Se presenta el caso clínico de un paciente que comenzó a presentar cefalea, vértigos, trastornos visuales y pérdida del equilibrio. Mediante la resonancia magnética se visualizó una imagen tumoral parietal izquierda de 3 cm diámetro, de localización extraaxial y contornos lobulados bien definidos, con gran captación no homogénea de contraste, rodeada de extenso edema perilesional. Se realizó angiotomografía, previa a la cirugía, en busca de irrigación y daño vascular. Se logró la resección de 95% de la lesión (grado II de Simpson, que incluyó duramadre adyacente infiltrada y respetó el seno longitudinal superior. Los resultados anatomopatológicos confirmaron que se trataba de un meningioma anaplásico de grado III, con criterio de tratamiento coadyuvante.The case report of a patient who began presenting headache, vertigos, visual disorders and loss of balance is presented. By means of the magnetic resonance a left tumoral parietal image of 3 cm diameter was visualized, of extra-axial localization and well defined lobulated contours, with great non-homogeneous zones of contrast, surrounded by extensive perilesional edema. An angiotomography was carried out, previous to the surgery, looking for irrigation and vascular compromise. The resection of 95% of the lesion was achieved (grade II of Simpson which included adjacent infiltrated dura madre and preserving the superior longitudinal sinus. Pathological results confirmed that it was an anaplastic meningioma grade III, with criterium for adyuvant treatment.

  1. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

  2. Anaplastic thyroid carcinoma in Denmark 1996-2012

    DEFF Research Database (Denmark)

    Hvilsom, Gitte Bjørn; Londero, Stefano Christian; Hahn, Christoffer Holst

    2018-01-01

    BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC...

  3. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    International Nuclear Information System (INIS)

    Sabet, Amir; Ahmadzadehfar, Hojjat; Herrlinger, Ulrich; Wilinek, Winfried; Biersack, Hans-Jürgen; Ezziddin, Samer

    2011-01-01

    A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition

  4. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    Directory of Open Access Journals (Sweden)

    Biersack Hans-Jürgen

    2011-08-01

    Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

  5. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

    Science.gov (United States)

    Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

    2015-01-01

    Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

  6. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara

    2007-01-01

    Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades......, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine...... phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542...

  7. The effect of low level laser on anaplastic thyroid cancer

    Science.gov (United States)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  8. Radiotherapy in anaplastic thyroid carcinoma: An Australian experience

    International Nuclear Information System (INIS)

    So, Kevin; Smith, Robin E.; Davis, Sidney R.

    2017-01-01

    Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period. A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013. Thirty patients (17 females and 13 males) were identified with a median age at presentation of 72 years. At presentation, six (20%), 14 (47%) and 10 (33%) patients had stage IVA, IVB and IVC disease respectively. Thirteen patients underwent radical surgical resection with five having microscopic residual (R1) and eight having macroscopic residual (R2) disease. Twenty-eight patients were offered radiotherapy with 27 proceeding with treatment. Of those who received radiotherapy, three, six and 18 were treated with adjuvant, definitive and palliative intent respectively. Six patients had concomitant chemotherapy of which three received trimodality therapy. Only one patient experienced a grade 3 toxicity (oesophagitis). Median survival was 5.3 months and at last follow-up or time of death, 19 of 27 (70.4%) maintained loco-regional control. All patients who had R1 surgical resections and radiotherapy had loco-regional control. Seven of nine (77.8%) and 12 of 18 (66.7%) achieved loco-regional control after receiving definitive or palliative radiotherapy, respectively. Our study suggests that radiotherapy with or without surgery or chemotherapy is well-tolerated and results in durable loco-regional control in a high proportion of patients with anaplastic thyroid carcinoma.

  9. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  10. Metronomic chemotherapy in anaplastic thyroid carcinoma: a potentially feasible alternative to therapeutic nihilism.

    Science.gov (United States)

    Revannasiddaiah, Swaroop; Madabhavi, Irappa; Bodh, Anita; Thakur, Priyanka; Sharma, Mukesh

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT), and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  11. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

    Science.gov (United States)

    Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

    2014-12-01

    The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

  12. Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion. Case report.

    Science.gov (United States)

    Takei, Hidehiro; Dauser, Robert; Su, Jack; Chintagumpala, Murali; Bhattacharjee, Meenakshi B; Jones, Jeremy; Adesina, Adekunle M

    2007-08-01

    The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

  13. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    International Nuclear Information System (INIS)

    Junor, E.J.; Paul, J.; Reed, N.S.

    1992-01-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author)

  14. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Junor, E.J.; Paul, J.; Reed, N.S. (Beatson Oncology Centre, Glasgow (United Kingdom))

    1992-04-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author).

  15. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.

    Science.gov (United States)

    Huang, Wei-Sheng; Liu, Shuangying; Zou, Dong; Thomas, Mathew; Wang, Yihan; Zhou, Tianjun; Romero, Jan; Kohlmann, Anna; Li, Feng; Qi, Jiwei; Cai, Lisi; Dwight, Timothy A; Xu, Yongjin; Xu, Rongsong; Dodd, Rory; Toms, Angela; Parillon, Lois; Lu, Xiaohui; Anjum, Rana; Zhang, Sen; Wang, Frank; Keats, Jeffrey; Wardwell, Scott D; Ning, Yaoyu; Xu, Qihong; Moran, Lauren E; Mohemmad, Qurish K; Jang, Hyun Gyung; Clackson, Tim; Narasimhan, Narayana I; Rivera, Victor M; Zhu, Xiaotian; Dalgarno, David; Shakespeare, William C

    2016-05-26

    In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

  16. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-07-01

    Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

  17. Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    He, Xiayun; Li, Duanshu; Hu, Chaosu; Wang, Zhuoying; Ying, Hongmei; Wu, Yi

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC. 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy. The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress. The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases

  18. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    International Nuclear Information System (INIS)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro

    1992-01-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. 18 F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author)

  19. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-04-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

  20. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    International Nuclear Information System (INIS)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

  1. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    Directory of Open Access Journals (Sweden)

    Shah Keerti V

    2005-02-01

    Full Text Available Abstract Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT, and 8 supratentorial primitive neuroectodermal tumors (sPNET using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3 was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.

  2. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    Science.gov (United States)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein. PMID:15717928

  3. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

    2017-07-01

    Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

  4. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  5. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

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    Zeliha Esin Celik

    2016-01-01

    Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

  6. Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics

    Directory of Open Access Journals (Sweden)

    Martina Tavarelli

    2017-10-01

    Full Text Available BackgroundAnaplastic thyroid cancer (ATC is a rare but extremely aggressive cancer of the thyroid, contributing up to 30–40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA.MethodsUsing the Sicilian Register of Thyroid Cancer (SRTC database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA.ResultsForty-three ATCs were identified in Sicily in the period 2002–2009. In our series only age <70 years at diagnosis (p = 0.01, coexistence with DTC (p = 0.027 and tumor size ≤6 cm (p = 0.012 were significant factors for increased survival at univariate analysis (only age at multivariate analysis. No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller.ConclusionThe similar ATC data observed in Sicily and USA (having different genetic background and lifestyle and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than

  7. THE MANAGEMENT OF AN ORAL ANAPLASTIC SARCOMA IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) USING INTRALESIONAL CHEMOTHERAPY.

    Science.gov (United States)

    Franklinos, Lydia H V; Masters, Nicholas; Feltrer, Yedra; Pocknell, Ann; Bolt, David M; Dakin, Stephanie; Berry, Karla; Molenaar, Fieke M

    2017-03-01

    An adult female captive pygmy hippopotamus (Choeropsis liberiensis) was diagnosed with an oral anaplastic sarcoma. The tumor was surgically debulked and intralesional chemotherapy with mitomycin C (0.4 mg/cm 3 of tumor) and cisplatin (1 mg/cm 3 of tumor) was administered. Chemotherapeutic treatment proved difficult due to the risks of repeated anesthetics and unknown drug efficacies. Marked proliferation of the mass was observed during estrus, and chemotherapy was repeated as an experimental treatment to slow tumor progression in order for the animal to remain in the species breeding program. Tumor proliferation was detected during the first trimester of pregnancy; however, in the lactation period, the mass became quiescent. No adverse reactions to chemotherapeutic drugs were observed and the animal continues to be monitored for tumor progression. This is the first report of an anaplastic sarcoma and of chemotherapy use in a pygmy hippopotamus and it highlights logistical considerations for treating neoplasia in this species.

  8. MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie

    2013-01-01

    distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, mi...

  9. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  10. Unusual presentation of anaplastic thyroid carcinoma with diffuse neck and thoracic nodules and hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Yun-Hsuan Lin

    2017-06-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is a highly aggressive endocrine tumor that can be expected to have a poor clinical outcome. Cutaneous metastases from ATC are rare and in the context of disseminated metastases. Owing to the rarity of the disease, no standard treatment has been documented, and few treatment modalities are effective. This case reports neck and thoracic cutaneous metastasis from ATC, with concurrent hyperthyroidism.

  11. Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

    Directory of Open Access Journals (Sweden)

    Khalid Riaz

    2013-01-01

    Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

  12. Juvenile Granulosa Cell Tumour: Anaplastic Variant with Omental Deposits

    Science.gov (United States)

    Rao, Anuradha C.K.; Monappa, Vidya

    2016-01-01

    Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all primary ovarian malignancies. It is a subtype of granulosa cell tumour that is almost always found during the first three decades of life. Histologically, it differs from the typical adult type of granulosa cell tumour. It accounts for 5-15% of all granulosa cell tumours, majority being unilateral. Herein, we describe an unusual histopathological variant of JGCT with numerous large cystic spaces, anaplasia and focal syncytiotrophoblast like giant cells. PMID:27042471

  13. Initiative For Thyroid Cancer Diagnosis: Decision Support System For Anaplast Thyroid Cancer

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    Jamil Ahmed Chandio

    2017-12-01

    Full Text Available Due to the high level exposure of biomedical image analysis, Medical image mining has become one of the well-established research area(s of machine learning. AI (Artificial Intelligence techniques have been vastly used to solve the complex classification problems of thyroid cancer. Since the persistence of copycat chromatin properties and unavailability of nuclei measurement techniques, it is really problem for doctors to determine the initial phases of nuclei enlargement and to assess the early changes of chromatin distribution. For example involvement of multiple transparent overlapping of nuclei may become the cause of confusion to infer the growth pattern of nuclei variations. Un-decidable nuclei eccentric properties may become one of the leading causes for misdiagnosis in Anaplast cancers. In-order to mitigate all above stated problems this paper proposes a novel methodology so called “Decision Support System for Anaplast Thyroid Cancer” and it proposes a medical data preparation algorithm AD (Analpast_Cancers which helps to select the appropriate features of Anaplast cancers such as (1 enlargement of nuclei, (2 persistence of irregularity in nuclei and existence of hyper chromatin. Proposed methodology comprises over four major layers, first layer deals with the noise reduction, detection of nuclei edges and object clusters. Second layer selects the features of object of interest such as nuclei enlargement, irregularity and hyper chromatin. Third layer constructs the decision model to extract the hidden patterns of disease associated variables and final layer evaluates the performance evaluation by using confusion matrix, precision and recall measures. The overall classification accuracy is measured about 97.2% with 10-k fold cross validation.

  14. Investigation of the results of therapy of anaplastic thyroid gland carcinomas

    International Nuclear Information System (INIS)

    Ooijen, M. van.

    1979-01-01

    The results of the treatment of 28 patients with an anaplastic thyroid gland carcinoma are investigated, to see whether an optimal therapy is indicated. The execution of an operation before radiotherapy does not appear to improve the prognosis (statistically this conclusion is not wholly justified). The presence of metastases at the beginning of the therapy gave rise to a worse prognosis than the absence of metastases. The combination treatment of chemotherapy and either surgery or radiotherapy was only applied to two patients so no conclusions can be made about its benefit. (C.F.)

  15. Emergency total thyroidectomy for bleeding anaplastic thyroid carcinoma: A viable option for palliation

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is a rare and highly aggressive thyroid neoplasm. Bleeding from tumor is an uncommon, but potentially life-threatening complication requiring sophisticated intervention facilities which are not usually available at odd hours in emergency. We report the case of a 45-year-old woman who presented with exsanguinating hemorrhage from ATC and was treated by emergency total thyroidectomy. The patient is well three months postoperatively. Emergency total thyroidectomy is a viable option for palliation in ATC presenting with bleeding.

  16. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

    Science.gov (United States)

    Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

    2014-01-01

    The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

  17. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  18. Recent advances and emerging therapies in anaplastic thyroid carcinoma [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Maria E. Cabanillas

    2018-01-01

    Full Text Available Anaplastic thyroid cancer is a rare and aggressive thyroid cancer with an overall survival measured in months. Because of this poor prognosis and often advanced age at presentation, these patients have traditionally been treated palliatively and referred for hospice. However, recent progress using novel therapies has energized the field, and several promising clinical trials are now available for these patients. This review will highlight this progress and the potential treatments that could pave the way to improved outcomes and quality of life for patients with this disease.

  19. Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

    Science.gov (United States)

    Lu, Xian; Zhang, Cunxian; Liu, Fang; Sung, C James; Steinhoff, Margaret M; Lawrence, W Dwayne

    2008-01-01

    Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.

  20. De novo anaplastic Kaposi sarcoma in a HIV-negative man: A case report and review of the literature

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    Slim Charfi

    2017-07-01

    Full Text Available Anaplastic Kaposi sarcoma is a rare variant of Kaposi’s and is typically associated with an agressive clinical course. We report a case of a 67-year-old HIV negative man, presented with multiple, pink nodules on the left ankle and a keratotic lesion of the right heel. Initial histopathological exam concluded to an undifferentiated sarcoma. A second biopsy was performed and concluded to an anaplastic Kaposi sarcoma. Immunohistochemical study was positive for HHV8. Treatment consisted on a tumor excision of all lesions. Our case and the review of the literature highlight the benefit of the non conservative surgical treatment for this aggressive form of Kaposi sarcoma.

  1. Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

    Science.gov (United States)

    Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

    2013-07-01

    Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

  2. Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

    Science.gov (United States)

    Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

    2018-01-30

    BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

  3. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan

    2002-01-01

    Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector mol...

  4. Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis

    DEFF Research Database (Denmark)

    Vindeløv, L L; Hansen, H H; Christensen, I J

    1980-01-01

    Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination and a ...

  5. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer

    NARCIS (Netherlands)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit.

  6. The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.

    Science.gov (United States)

    Pierie, Jean-Pierre E N; Muzikansky, Alona; Gaz, Randall D; Faquin, William C; Ott, Mark J

    2002-01-01

    Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P 45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age 45 Gy improves outcome.

  7. Small Cell Anaplastic Carcinoma of Primary Lung Tumor in a Miniature Schnauzer Dog

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    J. M. Kim, H. J. Han, B. Ku, G. Kim, K. M. Shim1, S. S. Kang2 and S. H. Choi*

    2011-04-01

    Full Text Available A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully resected although adhered part of CVC could not be completely resected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma.

  8. An extraneural primary anaplastic ependymoma at the subcutaneous inguinal region: Report of a rare case

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    Hamide Sayar

    2015-01-01

    Full Text Available Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm × 6.5 mm × 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot-like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region.

  9. An extraneural primary anaplastic ependymoma at the subcutaneous inguinal region: Report of a rare case.

    Science.gov (United States)

    Sayar, Hamide; Ersen, Ayca; Kurtul, Neslihan; Yazar, Mehmet Fatih; Balakan, Ozan

    2015-01-01

    Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm × 6.5 mm × 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot-like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region.

  10. A case of paraventricular anaplastic astrocytoma following radiation therapy for craniopharyngioma

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    Shimizu, Hiroaki; Fujiwara, Kazunori; Kobayashi, Shin-ichi; Kitahara, Masakazu (Ishinomaki Red Cross Hospital, Miyagi (Japan))

    1994-04-01

    A 20-year-old man received 60 Gy of radiation therapy after partial removal of craniopharyngioma. The patient had been well and follow-up CT scans did not show any aggravation for 16 years. Since his activity gradually diminished, he underwent an MRI at the age of 36 which revealed and abnormal mass on the corpus callosum. The mass lesion progressively enlarged thereafter, and was diagnosed as anaplastic astrocytoma by a stereotactic biopsy. He was treated with interferon, however, died at the age of 37. Review of the literature disclosed 19 other cases of glioma following radiation therapy for sellar/parasellar tumors. Characteristic features of these cases included (1) lowness of age compared to common glioma cases, (2) tendency to be malignant, (3) tendency to occur in areas where significant doses of radiation had been received previously. (author).

  11. Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

    Science.gov (United States)

    Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

    2015-09-01

    Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes.

  12. Endometrioid Adenocarcinoma Metastatic to the Thyroid, Presenting Like Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2011-01-01

    Full Text Available Metastasis of uterine cancer to the head and neck is extremely rare. We report what we believe to be the first documented case of endometrioid adenocarcinoma metastasizing to the thyroid gland. An 80-year-old woman was referred to the otolaryngology service with a rapidly growing neck mass. The mass appeared to originate from the thyroid gland. Her clinical presentation was consistent with anaplastic thyroid carcinoma. A tracheostomy was performed. An open biopsy established the diagnosis of moderately differentiated adenocarcinoma, consistent with a gynecologic primary. The patient had undergone a hysterectomy 5 years prior for endometrioid adenocarcinoma. The thyroid tumor histology and immunophenotype corresponded well with her prior endometrial carcinoma, indicating that the thyroid mass was a metastasis from the endometrial primary. Radiotherapy appears to offer good local disease control in this rare case of endometrioid adenocarcinoma metastatic to the thyroid.

  13. Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

    International Nuclear Information System (INIS)

    Kim, J.M.; Han, H.J.; Ku, B.; Kim, G.; Shim, K.M.; Kang, S.S.; Choi, S.H.

    2011-01-01

    A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

  14. Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

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    Gulati Michel

    2010-03-01

    Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

  15. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report.

    Science.gov (United States)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-06-13

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.

  16. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

    International Nuclear Information System (INIS)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-01-01

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child’s kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15–20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance

  17. Thirty-nine cases of intracranial hemangiopericytoma and anaplastic hemangiopericytoma: A retrospective review of MRI features and pathological findings

    International Nuclear Information System (INIS)

    Zhou, Jun-lin; Liu, Jian-li; Zhang, Jing; Zhang, Ming

    2012-01-01

    Objective: To retrospectively review the imaging features of surgically and pathologically confirmed intracranial hemangiopericytoma and anaplastic hemangiopericytoma. Methods: Thirty-nine cases of surgically and pathologically confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed retrospectively. The MRI features were compared with pathological findings in all cases. Results: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal (n = 20) or iso-signal (n = 1) on plain T1WI, and mixed high-low signal (n = 20) or iso-signal (n = 1) on plain T2WI. After contrast injection, marked heterogeneous enhancement was seen in 19 cases. Significant necrosis and cystic changes were seen in 16 cases, and the “dural tail sign” was found in two cases. Ten cases had bony destruction, and 16 showed significant peritumoral edema. In 18 cases of hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions showed mixed iso-low signal (n = 10) or iso-signal (n = 8) on plain T1WI, and mixed iso-high signal (n = 10) or iso-signal (n = 8) on plain T2WI. After contrast injection, significant uniform enhancement was seen in 10 cases. Significant necrosis and cystic changes were seen in seven cases, and “dural tail sign” was seen in six cases. Two cases had bony destruction. No case showed significant peritumoral edema. Pathological immunohistochemical Ki67 staining showed a concentration of ∼18.4% positive cells in anaplastic hemangiopericytoma, whereas in hemangiopericytoma it was 7.12%. Conclusion: Imaging findings of intracranial anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth tendency, more and easier bleeding, more necrosis, more cystic changes giving

  18. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

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    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  19. Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

    Science.gov (United States)

    Bonhomme, Benjamin; Godbert, Yann; Perot, Gaelle; Al Ghuzlan, Abir; Bardet, Stéphane; Belleannée, Geneviève; Crinière, Lise; Do Cao, Christine; Fouilloux, Geneviève; Guyetant, Serge; Kelly, Antony; Leboulleux, Sophie; Buffet, Camille; Leteurtre, Emmanuelle; Michels, Jean-Jacques; Tissier, Frédérique; Toubert, Marie-Elisabeth; Wassef, Michel; Pinard, Clémence; Hostein, Isabelle; Soubeyran, Isabelle

    2017-05-01

    Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic

  20. Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo.

    Science.gov (United States)

    Stenner, Frank; Liewen, Heike; Zweifel, Martin; Weber, Achim; Tchinda, Joelle; Bode, Beata; Samaras, Panagiotis; Bauer, Stefan; Knuth, Alexander; Renner, Christoph

    2008-09-01

    Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies, being responsible for the majority of thyroid cancer-related deaths. Despite multimodal therapy including surgery, chemotherapy, and radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived from tumor tissue of a 57-year-old man with thyroid cancer and pronounced neutrophilia, was established from surgically excised tumor tissue. The karyotype of the cell line shows many chromosomal abnormalities. Preclinical investigations have shown antitumor activity and effectiveness of the BRAF kinase inhibitor Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1 cell line these agents were applied in vitro and, showing activity in a cell culture model, were also used for in vivo treatment. Sorafenib had some clinical effect, namely normalization of leucocytosis, but had no sustained impact on subsequent tumor growth and development of distant metastasis. Molecular diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15 concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical benefit was seen with subsequent bortezomib therapy inducing a temporary halt to lymph node growth and a progression-free interval of 7 weeks. Our observations together with previous data from preclinical models could serve as a rationale for selecting those patients suffering from ATC most likely to benefit from targeted therapy. A prospective controlled randomized trial integrating kinase and proteasome inhibitors into a therapeutic regime for ATC is warranted.

  1. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    Science.gov (United States)

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  2. Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

    International Nuclear Information System (INIS)

    Ishikawa, Hitoshi; Mitsuhashi, Norio; Niibe, Hideo

    2002-01-01

    Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p<0.01). Calcification detected in AC was usually multiple and/or gross (mean size: φ8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC. (author)

  3. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Zhang, L.; Wang, H.; Liang, S.; Ma, C.

    2015-01-01

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  4. Anaplastic carcinoma of the pancreas: Is there a role for palliative surgical procedure?

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan

    2014-01-01

    Full Text Available Anaplastic carcinoma (AC or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF. Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  5. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dandekar, Prasad [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harmer, Clive; Barbachano, Yolanda [Department of Clinical Research and Development, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher [Head and Neck-Thyroid Unit, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom); Newbold, Kate [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom)

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  6. Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

    Directory of Open Access Journals (Sweden)

    Arai Hajime

    2007-08-01

    Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

  7. A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

    Science.gov (United States)

    Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David

    2012-07-01

    Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

  8. Pleomorphic xanthoastrocytoma with anaplastic features: one case report and review of literature

    Directory of Open Access Journals (Sweden)

    Cui-yun SUN

    2014-12-01

    Full Text Available Objective To investigate the clinicopathological features of pleomorphic xanthoastrocytoma with anaplastic features (PXA-A.  Methods The clinical manifestations, imaging, histopathological features, and immunophenotype were analyzed in one case of PXA-A, and relevant literatures were reviewed. Results The patient was a 58-year-old woman. MRI examination revealed a parenchyma mass with irregularly long T1 and long T2 signal in right temporal lobe and basal ganglia region. The border was clear and peritumoral edema was inconspicuous. The mesocephalon and right ventricle were compressed, and the midline was shifted to left. Enhanced MRI showed multiple flaky and nodular enhancement. Histologically, tumor cells showed remarkable cellular pleomorphism, and they were composed of mononuclear cells, multinuclear giant tumor cells, frothy tumor cells and spindle cells. Eosinophilic granular bodies and intranuclear inclusions were seen. Tumor cells in partial regions were intensively arranged, with obvious atypia. Immunohistochemical analysis showed immunoreactivity of the cells to glial fibrillary acidic protein (GFAP, Vimentin (Vim, S-100 protein (S-100, neuronal nuclei (NeuN and P53. The cells showed a negative reaction for synaptophysin (Syn, chromogranin A (CgA, neurofilament protein (NF, CD34 and isocitrate dehydrogenase 1 (IDH1. The Ki-67 label index was 8.20% .  Conclusions PXA-A is a rare tumor. The imaging features can offer a few diagnostic cues. However, a definite diagnosis depends on the histological and immunohistochemical features. doi: 10.3969/j.issn.1672-6731.2014.12.013

  9. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

    Directory of Open Access Journals (Sweden)

    Ahmed Idbaih

    Full Text Available Anaplastic oligodendrogliomas (AOD are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19(q10;p10, IDH1, IDH2, CIC and FUBP1 mutations.To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA," has been supported by the Institut National du Cancer (InCA. Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

  10. A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection.

    Science.gov (United States)

    Abe, Tomoyuki; Amano, Hironobu; Hanada, Keiji; Okazaki, Akihisa; Yonehara, Shuji; Kuranishi, Fumito; Nakahara, Masahiro; Kuroda, Yoshinori; Noriyuki, Toshio

    2016-08-01

    Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18 F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed.

  11. Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

    Science.gov (United States)

    Gómez Sáez, José Manuel; Jiménez-Fonseca, Paula; Santamaría Sandi, Javier; Capdevila Castillón, Jaume; Navarro González, Elena; Zafón Llopis, Carles; Ramón Y Cajal Asensio, Teresa; Riesco Eizaguirre, Garcilaso; Grande Pulido, Enrique; Galofré Ferrater, Juan Carlos

    2015-03-01

    Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean

  12. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

  13. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J.; Wainberg, Zev A.; Cho, Jae Yong; Schellens, Jan H.M.; Soria, Jean Charles; Wen, Patrick Y.; Zielinski, Christoph; Cabanillas, Maria E.; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E–mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E–mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease. PMID:29072975

  14. Dosimetric comparison between helical tomotherapy and volumetric modulated arc-therapy for non-anaplastic thyroid cancer treatment.

    Science.gov (United States)

    Khalifa, Jonathan; Vieillevigne, Laure; Boyrie, Sabrina; Ouali, Monia; Filleron, Thomas; Rives, Michel; Laprie, Anne

    2014-11-26

    To evaluate and compare dosimetric parameters of volumetric modulated arctherapy (VMAT) and helical tomotherapy (HT) for non-anaplastic thyroid cancer adjuvant radiotherapy. Twelve patients with non-anaplastic thyroid cancer at high risk of local relapse received adjuvant external beam radiotherapy with curative intent in our institution, using a two-dose level prescription with a simultaneous integrated boost approach. Each patient was re-planned by the same physicist twice using both VMAT and HT. Several dosimetric quality indexes were used: target coverage index (proportion of the target volume covered by the reference isodose), healthy tissue conformity index (proportion of the reference isodose volume including the target volume), conformation number (combining both previous indexes), Dice Similarity Coefficient (DSC), and homogeneity index ((D2%-D98%)/prescribed dose). Dose-volume histogram statistics were also compared. HT provided statistically better target coverage index and homogeneity index for low risk PTV in comparison with VMAT (respectively 0.99 vs. 0.97 (p=0.008) and 0.22 vs. 0.25 (p=0.016)). However, HT provided poorer results for healthy tissue conformity index, conformation number and DSC with low risk and high risk PTV. As regards organs at risk sparing, by comparison with VMAT, HT statistically decreased the D2% to medullary canal (25.3 Gy vs. 32.6 Gy (p=0.003)). Besides, HT allowed a slight sparing dose for the controlateral parotid (Dmean: 4.3 Gy vs. 6.6 Gy (p=0.032)) and for the controlateral sub-maxillary gland (Dmean: 29.1 Gy vs. 33.1 Gy (p=0.041)). Both VMAT and HT techniques for adjuvant treatment of non-anaplastic thyroid cancer provide globally attractive treatment plans with slight dosimetric differences. However, helical tomotherapy clearly provides a benefit in term of medullary canal sparing.

  15. The effect of 17-AAG on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer

    International Nuclear Information System (INIS)

    Wang Renfei; Tan Jian; Li Wei; Meng Zhaowei; Zheng Wei

    2012-01-01

    Objective: To investigate the effect of 17-allylamino-17-demethoxy geldanamycin (17-AAG) on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer (ATC) cells. Methods: Lipofection was used to transfect the recombinant plasmid, namely pcDNA3.1-NIS, into FRO cells (ATC cell line). A stable cell line NIS-FRO was obtained by G418 resistance selection. 125 I was added into the medium, and influx and efflux experiments were performed. Different time-radioactivity curves were drawn, and further analysis was performed between the non-transfected cells (the control group) and NIS-FRO cells treated with 1 μmol/L 17-AAG for 24 h. Student's t-test was used to analyze the data. Results: The iodine uptake ability of the NIS-FRO cells was significantly higher than that of the FRO cells (about 10.68 times, t=45.329, P<0.001). However, 125 I out-flowed rapidly when removed from the medium, and the retention rate of 125 I in the NIS-FRO cells was only 10.5% of the initial amount after 30 rin. After treatment with 1 μmol/L 17-AAG for 24 h, the 125 I uptake ability of NIS-FRO cells further increased. During the 20-60 min incubation with 125 I, the iodine uptake ability of 17-AAG treated NIS-FRO cells increased significantly with radioactive counts of 31771.8- 54815.5 per minute,which was much higher than that of the control group (24020.3-41293.8 per minute; t=3.096, 4.275, 3.055, 4.292 and 5.496, respectively, all P<0.05). The iodine uptake ability increased about 24.8%-35.5%. Furthermore, 5-30 min after removing the medium, the retention rates of 125 I in the 17-AAG treated NIS-FRO cells were significantly increased compared with those of the control group (32.7%-85.2% vs 10.5%-56.8%; t=22.801, 13.096, 19.631, 38.205, 43.519, 29.322, respectively, all P<0.01), and 125 I efflux was reduced. After 30 min, 125 I retention rate of the treatment group was 32.7%, which was 3.1 times higher than that of the control group. Conclusion: The iodine uptake ability can be

  16. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    Science.gov (United States)

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  17. Estimation of radiotherapy and MCNU versus radiotherapy and MCNU plus interferon-[beta] for the treatment of anaplastic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru; Ogasawara, Hidenori; Sugiyama, Kazuhiko; Maeda, Hitoshi; Harada, Kunyu (Hiroshima Univ. (Japan). School of Medicine)

    1993-02-01

    The efficacy of radiotherapy and MCNU (MR) was estimated in comparison with radiotherapy and MCNU plus interferon-[beta] (IMR) in 25 patients with anaplastic astrocytoma. The MR group received irradiation with 50[approx]60 Gy and intravenous administration of 2 mg/kg of MCNU on the initial day of irradiation and following every 6[approx]8 weeks interval. The IMR group also received the same regimen in addition to intravenous infusion of 2 x 10[sup 6] IU/m[sup 2] of interferon-[beta] for 5 serial days every eight weeks and following once every two weeks. There were no significant differences between the two groups in terms of background. The response rates of MR and IMR group were 38.5% and 66.7%, respectively. The times to tumor progression (TTP) in the two groups were 11.9[+-]5.8 months and 13.6[+-]7.7 months, respectively. Thus, IMR therapy seems to be more efficacious for patients with anaplastic astrocytoma than MR therapy, but further trials are necessary. (author).

  18. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma.

    NARCIS (Netherlands)

    Paepe, P. de; Baens, M; Krieken, J.H.J.M. van; Verhasselt, B.; Stul, M.; Simons, A.; Poppe, B.; Laureys, G.; Brons, P.P.T.; Vandenberghe, P.; Speleman, F.; Praet, M.; Wolf-Peeters, C. de; Marynen, P.; Wlodarska, I.

    2003-01-01

    We present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20-/CD138+

  19. An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

    Science.gov (United States)

    Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

    2015-07-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

  20. MGMT-STP27 Methylation Status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A Report from EORTC Study 26951

    NARCIS (Netherlands)

    van den Bent, Martin J.; Erdem-Eraslan, Lale; Idbaih, Ahmed; de Rooi, Johan; Eilers, Paul H. C.; Spliet, Wim G. M.; den Dunnen, Wilfred F. A.; Tijssen, Cees; Wesseling, Pieter; Smitt, Peter A. E. Sillevis; Kros, Johan M.; Gorlia, Thierry; French, Pim J.

    2013-01-01

    Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV

  1. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic oligodendrogliomas and oligoastrocytomas. A report from EORTC study 26951

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); L. Erdem-Eraslan (Lale); A. Idbaih (Ahmed); J.J. de Rooi (Johan); P.H.C. Eilers (Paul); W.G.M. Spliet (Wim); W.F.A. den Dunnen (Wilfred); C.C. Tijssen (Cees); P. Wesseling (Pieter); P.A.E. Sillevis Smitt (Peter); J.M. Kros (Johan); T.S. Gorlia (Thierry); P.J. French (Pim)

    2013-01-01

    textabstractPurpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/ oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more

  2. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951

    NARCIS (Netherlands)

    Bent, M.J. van den; Erdem-Eraslan, L.; Idbaih, A.; Rooi, J. de; Eilers, P.H.; Spliet, W.G.; Dunnen, W.F. den; Tijssen, C.; Wesseling, P.; Smitt, P.A.; Kros, J.M.; Gorlia, T.; French, P.J.

    2013-01-01

    PURPOSE: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV

  3. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    Science.gov (United States)

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This

  4. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

    Science.gov (United States)

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-09-04

    Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

  5. Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Aghajan, Yasmin; Yoon, Janet M; Crawford, John Ross

    2017-04-24

    Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. 131I therapy for hyperthyroidism and consequent appearing of anaplastic carcinoma of the thyroid: simple case-report or real pathophysiologic link?

    Directory of Open Access Journals (Sweden)

    G. Scanelli

    2013-05-01

    Full Text Available BACKGROUND 131I is usually employed for the therapy of hyperfunctioning thyroid diseases. This β-emitting radioisotope acts releasing its radiations in small tissue volumes, but it is mandatory to consider, also for the small doses, the carcinogenic risk, well documented with the high 131I dosages used to cure differentiated thyroid cancers. METHODS We describe a case of anaplastic thyroid carcinoma appeared 4 years after therapy with 131I for Graves’ disease. The patient was treated both surgically and with thyonamides for Graves’ disease 20 years before; thereafter she underwent simple nephrectomy owing to Grawitz disease. After some years of well being, she was treated with 131I for a relapse of Graves’ disease. Four years later, she was treated with interleukin-2 and TNF-α, owing to distant metastases (pancreas, liver and lung of Grawitz cancer. Some months later, because of a rapid enlargement of the thyroid gland, she was thyroidectomized and anaplastic thyroid cancer was histologically documented. DISCUSSION AND CONCLUSIONS It is very difficult to investigate the possible transformation of a benign thyroid lesion to a malignant one, and data from the literature are conflicting. Fractioned doses of 131I are known to induce less cancers than high doses: they allow DNA to repair. Nevertheless, in patients with altered or non valid genetic repair’s mechanisms (i.e. patients with p53 mutations and, for this reason, prone to develop cancers, even low doses of 131I can induce carcinogenetic effects. In a patient with a history of cancer, who subsequently develops hyperthyroidism, even low doses of 131I can induce anaplastic thyroid cancer; in these subjects, therefore, other treatments than 131I could be preferred for the therapy of Graves’ disease. In our peculiar case, moreover, some studies have noteworthy demonstrated that certain cytokines (IL-1, TGF-β1 e TNF-α can, rather than inhibit, induce anaplastic thyroid cancer cells

  7. Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC).

    Science.gov (United States)

    Liu, Yuexin; Yan, Jinyin; Han, Xiaochen; Hu, Wanning

    2015-01-01

    Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic have anticancer activity. In this study, the apoptotic effects of Garlic-derived compound S-allylmercaptocysteine (SAMC) were investigated in 8305C human anaplastic thyroid carcinoma cells. The cell line 8305C (HPACC) were treated with SAMC and the MTT assay, flow cytometry (FCM), electron microscope method were used to test cell cycle, inhibitory rate and morphologic changes respectively. HPACC-8305C cells were suppressed after exposure to SAMC of 0.02 mg/ml, 0.06 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P< 0.05). SAMC could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P< 0.05). After exposure to SAMC at 0.02 mg/ml for 24 hours, HPACC-8305C cells showed typical morphologic change. SAMC inhibits the growth of HPACC-8305C cells by induction of apoptotic cell death and inhibit telomerase activity, which appears to account for its anti-cancer activity.

  8. [Anaplastic carcinoma of the thyroid at the Instituto Nacional de la Nutrición Salvador Zubirán].

    Science.gov (United States)

    Sierra, M; Gamboa-Domínguez, A; Herrera, M F; Barredo-Prieto, B; Alvarado de la Barrera, C; Llorente, L; Pérez-Enriquez, B; Rivera, R; González, O; Rull, J A

    1997-01-01

    Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a median survival rate of 6 months. To analyze presentation, treatment, morphology, immunohistochemistry, and nuclear DNA analysis of a cohort of patients with ATC. Twelve patients with ATC (11 female) with a mean age of 65 years were seen at our hospital from 1970-1995. The data were obtained from the clinical records and the morphology, immunohistochemic studies and DNA pattern were performed in slides obtained from archival specimens. Previous or coexisting thyroide disease was documented in 10 patients (9 multinodular goiters and one Grave's). The most frequent presentation was a rapidly growing tumor associated with dysphagia, cervical pain, hoarseness and dyspnea. A cold thyroid nodule was detected by thyroid scan in 10 patients. The most frequent subtype was the spindle cell variety. Papillary thyroid carcinoma coexisted in eight cases, two of them corresponded to the tall cell variant. Reactivity for S-100 protein and vimentin was studied in six patients: all were positive for S-100 protein and vimentin, 5/6 for epithelial membrane antigen, half for carcinoembriogenic antigen, 2/6 for thyroglobulin and calcitonin, and one for neuronal specific enolase. These six tumors showed a diploid DNA pattern. Tumor resection was achieved in 2/11 and none survived six years after diagnosis. ATC is a highly aggressive tumor coexisting with thyroid pathologies. Spindle cell variant is the most frequent with positive reactivity for S-100 protein, vimentin and epithelial membrane antigen. Most tumors have a diploid DNA content.

  9. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju

    2017-01-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib......-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review...... (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated...

  10. CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Li-Chi Huang

    2018-01-01

    Full Text Available Anaplastic carcinoma of the thyroid (ATC, also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P=0.017 in CCLE and P=0.001 in TCGA. Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.

  11. BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

    Science.gov (United States)

    Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

    2012-01-01

    Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

  12. Melanoma maligno anaplásico em um eqüino Anaplastic malignant melanoma in a horse

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    Daniel Ricardo Rissi

    2008-10-01

    Full Text Available Descreve-se um caso de melanoma maligno anaplásico em uma égua Crioula, tordilha, com 10 anos de idade, com histórico clínico de apatia, perda de peso progressiva, febre, anorexia e dispnéia. Múltiplas massas pigmentadas e não-pigmentadas, bem delimitadas ou infiltrativas, foram observadas no tecido subcutâneo e em vários órgãos. Histologicamente o neoplasma era composto de populações de células fusiformes, redondas ou poliédricas e, menos freqüentemente, de células multinucleadas e "células em anel de sinete". O diagnóstico foi realizado com base nos achados clinicopatológicos e confirmado pela microscopia eletrônica de transmissão.A case of anaplastic malignant melanoma in a 10-year-old gray mare is described. Clinical signs included depression, progressive weight loss, fever, anorexia, and dyspnea. Multiple circumscribed or infiltrative, pigmented, and non-pigmented tumors were observed in subcutaneous tissue and in several organs. Histological examination revealed a marked variation in neoplastic cell population, which was composed by spindle, round, polyhedrical, and less frequently, multinucleated or signet ring cells. The diagnostic was based up on clinical and pathological findings, and confirmed by transmission electronic microscopy.

  13. Anaplastic myxopapillary ependymoma in an infant: Case report and literature review

    OpenAIRE

    Trivedi, Darshan; Xiong, Zhenggang

    2017-01-01

    A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyp...

  14. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

    International Nuclear Information System (INIS)

    Shao, Mingchen; Geng, Yiwei; Lu, Peng; Xi, Ying; Wei, Sidong; Wang, Liuxing; Fan, Qingxia; Ma, Wang

    2015-01-01

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells

  15. Multimodal 18F-Fluciclovine PET/MRI and Ultrasound-Guided Neurosurgery of an Anaplastic Oligodendroglioma.

    Science.gov (United States)

    Karlberg, Anna; Berntsen, Erik Magnus; Johansen, Håkon; Myrthue, Mariane; Skjulsvik, Anne Jarstein; Reinertsen, Ingerid; Esmaeili, Morteza; Dai, Hong Yan; Xiao, Yiming; Rivaz, Hassan; Borghammer, Per; Solheim, Ole; Eikenes, Live

    2017-12-01

    Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracer 18 F-fluciclovine ( 18 F-FACBC) for intraoperative image-guided surgery. A previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II. 18 F-Fluciclovine uptake was found in parts of the tumor where regional WHO grade, cell proliferation, and cell densities were highest. This finding suggests that PET/MRI with this tracer could be used to improve accuracy in histopathologic tissue sampling and grading, and possibly for guiding treatments targeting the most malignant part of extensive and eloquent gliomas. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

    Science.gov (United States)

    McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

  17. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

    Directory of Open Access Journals (Sweden)

    Barbara Klink

    Full Text Available Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

  18. Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study

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    Stuart L. Cramer

    2018-01-01

    Full Text Available Therapy for rhabdomyosarcoma (RMS has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types. However, malignancies common in children, thus far, have been less amenable to such targeted therapies. This report describes the clinical course of an 8-year-old female with embryonal RMS having anaplastic features. This patient experienced multiple relapses after receiving various established and experimental therapies. Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2 genes, each of which contributes to epigenetic regulation and interacts with or modifies the activity of histone deacetylases (HDAC. Based on these findings, the patient was treated with the HDAC inhibitor vorinostat as a single agent. The tumor responded transiently followed by subsequent disease progression. We also examined the efficacy of vorinostat in a patient-derived xenograft (PDX model developed using tumor tissue obtained from the patient’s most recent tumor resection. The antitumor activity of vorinostat observed with the PDX model reflected clinical observations in that obvious areas of tumor necrosis were evident following exposure to vorinostat. Histologic sections of tumors harvested from PDX tumor-bearing mice treated with vorinostat demonstrated induction of necrosis by this agent. We propose that the evaluation of clinical efficacy in this type of preclinical model merits further evaluation to determine if PDX models predict tumor sensitivity to specific agents and/or combination therapies.

  19. Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3β/ANG Signaling Pathway in Anaplastic Thyroid Cancer

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    Zhijian Jin

    2017-12-01

    Full Text Available Background/Aims: Anaplastic thyroid carcinoma (ATC is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI, has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. Methods: In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3β inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. Results: Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3β. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3β attenuated the anti-angiogenic ability of Apatinib. Conclusion: Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3β/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC.

  20. Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell

    Directory of Open Access Journals (Sweden)

    Regina A. Mangieri

    2017-08-01

    Full Text Available Anaplastic lymphoma kinase (ALK is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD. Ethanol induces adaptations in glutamatergic synapses onto nucleus accumbens shell (NAcSh medium spiny neurons (MSNs, and putative targets for treating AUD may be validated for further development by assessing how their manipulation modulates accumbal glutamatergic synaptic transmission and plasticity. Here, we report that Alk knockout (AlkKO mice consumed greater doses of ethanol, relative to wild-type (AlkWT mice, in an operant self-administration model. Using ex vivo electrophysiology to examine excitatory synaptic transmission and plasticity at NAcSh MSNs that express dopamine D1 receptors (D1MSNs, we found that the amplitude of spontaneous excitatory post-synaptic currents (EPSCs in NAcSh D1MSNs was elevated in AlkKO mice and in the presence of an ALK inhibitor, TAE684. Furthermore, when ALK was absent or inhibited, glutamatergic synaptic plasticity – long-term depression of evoked EPSCs – in D1MSNs was attenuated. Thus, loss of ALK activity in mice is associated with elevated ethanol consumption and enhanced excitatory transmission in NAcSh D1MSNs. These findings add to the mounting evidence of a relationship between excitatory synaptic transmission onto NAcSh D1MSNs and ethanol consumption, point toward ALK as one important molecular mediator of this interaction, and further validate ALK as a target for therapeutic intervention in the treatment of AUD.

  1. Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

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    Jerzy Sowinski

    2009-01-01

    Full Text Available We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1 and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5% in the comparison with the follicular areas (2 +/- 1%. The evaluation of the thyroid transcription factor 1 (TTF-1 expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.

  2. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  3. Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Jun Osugi

    2016-01-01

    Full Text Available Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.

  4. Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

    Science.gov (United States)

    Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

    2018-04-06

    Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and

  5. Impact of 9p deletion and p16, Cyclin D1, and Myc hyperexpression on the outcome of anaplastic oligodendrogliomas.

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    Karine Michaud

    Full Text Available To study the presence of 9p deletion and p16, cyclin D1 and Myc expression and their respective diagnostic and prognostic interest in oligodendrogliomas.We analyzed a retrospective series of 40 consecutive anaplastic oligodendrogliomas (OIII from a single institution and compared them to a control series of 10 low grade oligodendrogliomas (OII. Automated FISH analysis of chromosome 9p status and immunohistochemistry for p16, cyclin D1 and Myc was performed for all cases and correlated with clinical and histological data, event free survival (EFS and overall survival (OS.Chromosome 9p deletion was observed in 55% of OIII (22/40 but not in OII. Deletion was highly correlated to EFS (median = 29 versus 53 months, p<0.0001 and OS (median = 48 versus 83 months, p<0.0001 in both the total cohort and the OIII population. In 9p non-deleted oligodendrogliomas, p16 hyperexpression correlated with a shorter OS (p = 0.02 in OII and p = 0.0001 in OIII whereas lack of p16 expression was correlated to a shorter EFS and OS in 9p deleted OIII (p = 0.001 and p = 0.0002 respectively. Expression of Cyclin D1 was significantly higher in OIII (median expression 45% versus 14% for OII, p = 0.0006 and was correlated with MIB-1 expression (p<0.0001, vascular proliferation (p = 0.002, tumor necrosis (p = 0.04 and a shorter EFS in the total cohort (p = 0.05. Hyperexpression of Myc was correlated to grade (median expression 27% in OII versus 35% in OIII, p = 0.03, and to a shorter EFS in 9p non-deleted OIII (p = 0.01.Chromosome 9p deletion identifies a subset of OIII with significantly worse prognosis. The combination of 9p status and p16 expression level identifies two distinct OIII populations with divergent prognosis. Hyperexpression of Bcl1 and Myc appears highly linked to anaplasia but the prognostic value is unclear and should be investigated further.

  6. In vitro identification and characterization of CD133(pos cancer stem-like cells in anaplastic thyroid carcinoma cell lines.

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    Giovanni Zito

    Full Text Available Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs. Anaplastic Thyroid Carcinoma (ATC is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown.ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively. These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg. Furthermore, ARO/CD133(pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos in comparison to ARO/CD133(neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos when compared with ARO/CD133(neg cells.We describe CD133(pos cells in ATC cell lines. ARO/CD133(pos cells exhibit stem cell-like features--such as high proliferation, self-renewal ability, expression of OCT-4--and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in

  7. Controversies on Hodgkin's disease and anaplastic large cell lymphoma. Hematopathology Study Group of the Società Italiana di Anatomia Patologica.

    Science.gov (United States)

    Pileri, S

    1994-01-01

    Just one year ago the Italian Society of Pathology (S.I.A.P.) created a Study Group which included members of the most active Italian hematopathology teams. Prof. Pasquale Calapso was asked to chair the Group and Prof. Stefano Pileri to take care of secretarial duties. The aim of the Group is to spread hematopathologic knowledge among young pathologists and to promote activities that can contribute to updating Italian pathologists on topics of both speculative and diagnostic interest. The first Workshop of the S.I.A.P. Hematopathology Group was held at the Palazzo dei Congressi in Bologna, November 20, 1993. About 150 pathologists from all over Italy took part in the meeting, which consisted of two sections devoted to: a) discussion of the boundaries between Hodgkin's disease and non-Hodgkin's lymphomas, and b) a case seminar illustrating the impact of immunohistochemistry in the diagnosis of bone-marrow biopsy. The first section included 5 presentations and a Round Table chaired by Prof. Luciano Fiore-Donati. Below, the contributors to this section summarize the content of their presentations, which were aimed at answering specific questions the Organizers had put to them.

  8. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C.; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-01-01

    Background Optimal treatment and precise classification for anaplastic glioma are needed. Methods The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Results Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6–10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4–5.1] y vs 4.4 [3.3–5.3) y), PFS (2.5 [1.3–3.5] y vs 2.7 [1.9–3.2] y), and OS (8 [5.5–10.3] y vs 6.5 [5.4–8.3] y). Oligodendroglial versus astrocytic histology—but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status—revealed a strong prognostic value of CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17–0.92], P = .031). In CIMPneg. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. Conclusions There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. Trial Registration: clinicaltrials.gov Identifier: NCT00717210. PMID:27370396

  9. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-11-01

    Optimal treatment and precise classification for anaplastic glioma are needed. The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMP pos with (CIMP codel ) versus without 1p/19 co-deletion (CIMP non-codel ) versus CIMP neg . but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMP codel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMP neg . tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. clinicaltrials.gov Identifier: NCT00717210. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung

    International Nuclear Information System (INIS)

    Enig, B.; Winther, E.; Hessov, I.; Aarhus Univ.

    1986-01-01

    The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p>0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight).There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment. (orig.)

  11. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

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    Antonietta R. Farina

    2013-01-01

    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

  12. Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials hit 88/89 and hit 91

    International Nuclear Information System (INIS)

    Timmermann, Beate; Kortmann, Rolf-Dieter; Kuehl, Joachim; Meisner, Christoph; Slavc, Irene; Pietsch, Thorsten; Bamberg, Michael

    2000-01-01

    Purpose: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. Methods and Materials: Fifty-five children (n = 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before (n = 40) or after irradiation (n = 15). The irradiation volume encompassed either the neuraxis followed by a boost to the primary tumor site (n = 40) or the tumor region only (n = 13). No radiotherapy was administered in two patients. Results: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. Conclusions: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study

  13. Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): Results of North Central Cancer Treatment Group trial 98-72-51

    International Nuclear Information System (INIS)

    Rao, Ravi D.; Krishnan, Sunil; Fitch, Tom R.; Schomberg, Paula J.; Dinapoli, Robert P.; Nordstrom, Kathleen; Scheithauer, Bernd; O'Fallon, Judith R.; Maurer, Matthew J. M.S.; Buckner, Jan C.

    2005-01-01

    Purpose: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Methods and materials: Therapy consisted of carmustine (40 mg/m 2 /d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m 2 /d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. Results: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Conclusion: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma

  14. Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

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    DiBonaventura MD

    2017-12-01

    Full Text Available Marco D DiBonaventura,1 William Wong,2 Bijal Shah-Manek,3,4 Mathias Schulz2 1Ipsos Healthcare, Global Evidence, Value & Access, New York, NY, 2Genentech, US Medical Affairs, San Francisco, CA, 3Ipsos Healthcare, Global Evidence, Value & Access, San Francisco, CA, 4College of Pharmacy, Touro University California, CA, USA Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95 in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor, collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results: A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male. The patients in our sample were older (median age of 60 vs 53 years, were more likely to be current smokers (12% vs 1%, had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0, and were less likely to have an adenocarcinoma histology (83% vs 96% relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively as was the disease control rate (89.9% vs 78.8%, respectively, though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0% and dose reductions (3.4% due to adverse events were uncommon in alectinib.Conclusion: Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically

  15. Comparing outcomes in poorly-differentiated versus anaplastic thyroid cancers treated with radiation: A surveillance, epidemiology, and end results analysis

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    Shruthi Arora

    2014-01-01

    Conclusion: This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative were associated with improved CSS in both histologies.

  16. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

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    Chien-Chih Ke

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  17. Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Shimada M

    2017-06-01

    Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

  18. Anaplastic Thyroid Cancer: The Addition of Systemic Chemotherapy to Radiotherapy Led to an Observed Improvement in Survival—A Single Centre Experience and Review of the Literature

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    Natalie M. Lowe

    2014-01-01

    Full Text Available Introduction. Anaplastic thyroid carcinoma (ATC is rare yet accounts for up to 50% of all thyroid cancer deaths. This study reviews outcomes of patients with confirmed ATC referred to a tertiary oncology centre plus reviews the literature to explore how poor outcomes may be improved. Materials and Methods. The management and outcomes of 20 patients with ATC were reviewed. Results. Median age at diagnosis was 69.5 years. 19 patients died due to ATC, 40% of whom died from asphyxiation. Median survival for all cases was 59 days. Patients who had previous surgery prior to other treatment modalities had a longer median survival overall compared to those who had not had previous surgery (142 days compared to 59 days and produced the one long-term survivor. Chemotherapy followed by radiotherapy (without previous surgery was associated with longer median survival (220 days. Palliative radiotherapy alone did not decrease the rate of death by asphyxiation when compared to other single modality treatments. Conclusion. Multimodality treatment including surgery when feasible remains the best strategy to improve survival and prevent death from asphyxiation in the management of ATC. The addition of chemotherapy to our institutional protocol led to improved survival but prognosis remains very poor.

  19. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

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    Maria Graziella Catalano

    2016-01-01

    Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

  20. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis

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    Walter Arancio

    2015-01-01

    Full Text Available It has been suggested that cancer stem cells (CSC may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2, in the control cell cycle (TP53, CCND1, and in mitochondrial activity (COX8A. The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated.

  1. Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

    Science.gov (United States)

    Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

    2016-09-01

    Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2

    International Nuclear Information System (INIS)

    Miura, Kotaro; Kimura, Kenjiro; Amano, Ryosuke; Yamazoe, Sadaaki; Ohira, Go; Murata, Akihiro; Nishio, Kohei; Hasegawa, Tsuyoshi; Yashiro, Masakazu; Nakata, Bunzo; Ohira, Masaichi; Hirakawa, Kosei

    2016-01-01

    Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer

  3. O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

    Science.gov (United States)

    Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

    2014-01-01

    Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448

  4. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Jürgen; Deimling, Andreas von; Hartmann, Christian

    2011-01-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  5. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    International Nuclear Information System (INIS)

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y.; Hayashi, Y.

    2012-01-01

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  6. Cognition and Quality of Life After Chemotherapy Plus Radiotherapy (RT) vs. RT for Pure and Mixed Anaplastic Oligodendrogliomas: Radiation Therapy Oncology Group Trial 9402

    International Nuclear Information System (INIS)

    Wang Meihua; Cairncross, Gregory; Shaw, Edward

    2010-01-01

    Purpose: Radiation Therapy Oncology Group 9402 compared procarbazine, lomustine, and vincristine (PCV) chemotherapy plus radiation therapy (PCV + RT) vs. RT alone for anaplastic oligodendroglioma. Here we report longitudinal changes in cognition and quality of life, effects of patient factors and treatments on cognition, quality of life and survival, and prognostic implications of cognition and quality of life. Methods and Materials: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL). Scores were analyzed for survivors and within 5 years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those who died, MMSE scores remained stable initially, whereas B-QOL slowly declined; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (p = 0.0413 for MMSE; p = 0.0016 for B-QOL) and were superior with age <50 years (p < 0.001 for MMSE; p = 0.0554 for B-QOL) and Karnofsky Performance Score (KPS) 80-100 (p < 0.001). Younger age and higher KPS were associated with longer survival. After adjusting for patient factors and drop-out, survival was longer after PCV + RT (HR = 0.66, 95% CI = 0.49-0.9, p = 0.0084; HR = 0.74, 95% CI = 0.54-1.01, p = 0.0592) in models with MMSE and B-QOL. In addition, there were no differences in MMSE and B-QOL scores between arms (p = 0.4752 and p = 0.2767, respectively); higher scores predicted longer survival. Conclusion: MMSE and B-QOL scores held steady in the upper range in both arms for survivors. Younger, fitter patients had better MMSE and B-QOL and longer survival.

  7. Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

    Science.gov (United States)

    DiBonaventura, Marco D; Wong, William; Shah-Manek, Bijal; Schulz, Mathias

    2018-01-01

    Background Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor), collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male). The patients in our sample were older (median age of 60 vs 53 years), were more likely to be current smokers (12% vs 1%), had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0), and were less likely to have an adenocarcinoma histology (83% vs 96%) relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0%) and dose reductions (3.4%) due to adverse events were uncommon in alectinib. Conclusion Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically diverse than patients in published trials. Real-world response rates were high and similar to those reported in clinical studies, though there is some variation by patient characteristics. Alectinib was well tolerated in clinical practice as reflected by the rates of discontinuation, dose reductions, and dose interruptions. PMID

  8. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E., E-mail: Stephanie.Combs@med.uni-heidelberg.de [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Schulz-Ertner, Daniela [Radiologisches Institut, Markuskrankenhaus Frankfurt, Frankfurt am Main (Germany); Debus, Juergen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Deimling, Andreas von; Hartmann, Christian [Department of Neuropathology, Institute for Pathology, University Hospital of Heidelberg, Heidelberg (Germany); Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg (Germany)

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  9. Large deviations

    CERN Document Server

    Varadhan, S R S

    2016-01-01

    The theory of large deviations deals with rates at which probabilities of certain events decay as a natural parameter in the problem varies. This book, which is based on a graduate course on large deviations at the Courant Institute, focuses on three concrete sets of examples: (i) diffusions with small noise and the exit problem, (ii) large time behavior of Markov processes and their connection to the Feynman-Kac formula and the related large deviation behavior of the number of distinct sites visited by a random walk, and (iii) interacting particle systems, their scaling limits, and large deviations from their expected limits. For the most part the examples are worked out in detail, and in the process the subject of large deviations is developed. The book will give the reader a flavor of how large deviation theory can help in problems that are not posed directly in terms of large deviations. The reader is assumed to have some familiarity with probability, Markov processes, and interacting particle systems.

  10. Novel covalent modification of human anaplastic lymphoma kinase (ALK and potentiation of crizotinib-mediated inhibition of ALK activity by BNP7787

    Directory of Open Access Journals (Sweden)

    Parker AR

    2015-02-01

    Full Text Available Aulma R Parker,1 Pavankumar N Petluru,1 Vicki L Nienaber,2 Min Zhao,1 Philippe Y Ayala,1 John Badger,2 Barbara Chie-Leon,2 Vandana Sridhar,2 Cheyenne Logan,2 Harry Kochat,1 Frederick H Hausheer1 1BioNumerik Pharmaceuticals, Inc., San Antonio, TX, USA; 2Zenobia Therapeutics, Inc., La Jolla, CA, USA Abstract: BNP7787 (Tavocept, disodium 2,2’-dithio-bis-ethanesulfonate is a novel, investigational, water-soluble disulfide that is well-tolerated and nontoxic. In separate randomized multicenter Phase II and Phase III clinical trials in non-small-cell lung cancer (NSCLC patients, treatment with BNP7787 in combination with standard chemotherapy resulted in substantial increases in the overall survival of patients with advanced adenocarcinoma of the lung in the first-line treatment setting. We hypothesized that BNP7787 might interact with and modify human anaplastic lymphoma kinase (ALK. At least seven different variants of ALK fusions with the gene encoding the echinoderm microtubule-associated protein-like 4 (EML4 are known to occur in NSCLC. EML4–ALK fusions are thought to account for approximately 3% of NSCLC cases. Herein, we report the covalent modification of the kinase domain of human ALK by a BNP7787-derived mesna moiety and the functional consequences of this modification in ALK assays evaluating kinase activity. The kinase domain of the ALK protein crystallizes as a monomer, and BNP7787-derived mesna-cysteine adducts were observed at Cys 1235 and Cys 1156. The BNP7787-derived mesna adduct at Cys 1156 is located in close proximity to the active site and results in substantial disorder of the P-loop and activation loop (A-loop. Comparison with the P-loop of apo-ALK suggests that the BNP7787-derived mesna adduct at Cys 1156 interferes with the positioning of Phe 1127 into a small pocket now occupied by mesna, resulting in a destabilization of the loop's binding orientation. Additionally, in vitro kinase activity assays indicate that BNP7787

  11. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

    Science.gov (United States)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju; Reckamp, Karen L; Hansen, Karin Holmskov; Kim, Sang-We; Huber, Rudolf M; West, Howard L; Groen, Harry J M; Hochmair, Maximilian J; Leighl, Natasha B; Gettinger, Scott N; Langer, Corey J; Paz-Ares Rodríguez, Luis G; Smit, Egbert F; Kim, Edward S; Reichmann, William; Haluska, Frank G; Kerstein, David; Camidge, D Ross

    2017-08-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed

  12. Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation

    Directory of Open Access Journals (Sweden)

    Wang H

    2018-05-01

    Full Text Available Han Wang,1–3 Yao Wang,1–3 Wentao Guo,4 Bin Du,1–3 Xiaobing Huang,1–3 Riping Wu,1–3 Baoyu Yang,1–3 Xiaoyan Lin,1–3,5 Yilan Wu6 1Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Stem Cell Research Institute, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, People’s Republic of China; 4School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Graduate School of Education, Fujian Medical University, Fuzhou, People’s Republic of China; 6School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Background: Mutated anaplastic lymphoma kinase (ALK drives the development of advanced non-small cell lung cancer (NSCLC. Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02, which demonstrated potent effects against the G1202R mutation. Methods: Molecular docking, conventional molecular dynamics (MD simulations, free energy calculations, and umbrella sampling (US simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R mutation. Results: JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib

  13. A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain

    International Nuclear Information System (INIS)

    Halperin, Edward C.; Herndon, James; Schold, S. Clifford; Brown, Mark; Vick, Nicholas; Cairncross, J. Gregory; Macdonald, David R.; Gaspar, Laurie; Fischer, Barbara; Dropcho, Edward; Rosenfeld, Steven; Morowitz, Richard; Piepmeier, Joseph; Hait, William; Byrne, Thomas; Salter, Merle; Imperato, Joseph; Khandekar, Janardan; Paleologos, Nina; Burger, Peter; Bentel, Gunilla C.; Friedman, Allan

    1996-01-01

    Purpose: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were ≥ 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) ≥ 60%. Methods and Materials: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m 2 ) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m 2 ) given at 6-week intervals or 6-mercaptopurine (6-MP, 750 mg/m 2 IV daily for 3 days every 6 weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average age 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS ≥ 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age ≥ 45 years (b) KPS < 90%; (c) GBM/Gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). Conclusions: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a

  14. Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.

    Science.gov (United States)

    Hurry, Manjusha; Zhou, Zheng-Yi; Zhang, Jie; Zhang, Chenxue; Fan, Liangyi; Rebeira, Mayvis; Xie, Jipan

    2016-10-01

    To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective. A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings. Based on the willingness-to-pay threshold for

  15. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

    Science.gov (United States)

    Chang, Susan; Zhang, Peixin; Cairncross, J Gregory; Gilbert, Mark R; Bahary, Jean-Paul; Dolinskas, Carol A; Chakravarti, Arnab; Aldape, Kenneth D; Bell, Erica H; Schiff, David; Jaeckle, Kurt; Brown, Paul D; Barger, Geoffrey R; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh

    2017-02-01

    The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

    Science.gov (United States)

    Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

    2014-11-01

    Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

  17. Large deviations

    CERN Document Server

    Deuschel, Jean-Dominique; Deuschel, Jean-Dominique

    2001-01-01

    This is the second printing of the book first published in 1988. The first four chapters of the volume are based on lectures given by Stroock at MIT in 1987. They form an introduction to the basic ideas of the theory of large deviations and make a suitable package on which to base a semester-length course for advanced graduate students with a strong background in analysis and some probability theory. A large selection of exercises presents important material and many applications. The last two chapters present various non-uniform results (Chapter 5) and outline the analytic approach that allow

  18. Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

    2017-09-01

    As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

  19. Large ethics.

    Science.gov (United States)

    Chambers, David W

    2008-01-01

    This essay presents an alternative to the traditional view that ethics means judging individual behavior against standards of right and wrong. Instead, ethics is understood as creating ethical communities through the promises we make to each other. The "aim" of ethics is to demonstrate in our own behavior a credible willingness to work to create a mutually better world. The "game" of ethics then becomes searching for strategies that overlap with others' strategies so that we are all better for intending to act on a basis of reciprocal trust. This is a difficult process because we have partial, simultaneous, shifting, and inconsistent views of the world. But despite the reality that we each "frame" ethics in personal terms, it is still possible to create sufficient common understanding to prosper together. Large ethics does not make it a prerequisite for moral behavior that everyone adheres to a universally agreed set of ethical principles; all that is necessary is sufficient overlap in commitment to searching for better alternatives.

  20. Radiotherapy quality assurance for the RTOG 0834/EORTC 26053-22054/NCIC CTG CEC.1/CATNON intergroup trial "concurrent and adjuvant temozolomide chemotherapy in newly diagnosed non-1p/19q deleted anaplastic glioma": Individual case review analysis.

    Science.gov (United States)

    Abrunhosa-Branquinho, André N; Bar-Deroma, Raquel; Collette, Sandra; Clementel, Enrico; Liu, Yan; Hurkmans, Coen W; Feuvret, Loïc; Van Beek, Karen; van den Bent, Martin; Baumert, Brigitta G; Weber, Damien C

    2018-03-29

    The EORTC phase III 26053-22054/ RTOG 0834/NCIC CTG CEC.1/CATNON intergroup trial was designed to evaluate the impact on concurrent and adjuvant temozolomide chemotherapy in newly diagnosed non-1p/19q deleted anaplastic gliomas. The primary endpoint was overall survival. We report the results of retrospective individual case reviews (ICRs) for the first patient randomized per institution to detect the compliance with the study protocol. Sixty-nine institutions were required to submit the radiotherapy plan of their first randomized patient. Full digital datasets uploaded to the EORTC server were assessed by three independent and blinded reviewers through the EORTC radiotherapy quality assurance platform. Sixty-two (90%) of sixty-nine ICRs were received and assessable. Of the 62 cases, 22 were evaluated as per protocol (35.5%), 11 as acceptable variation (17.7%) and 29 were classified as unacceptable variations (46.8%). Most common unacceptable variations were related to the PTV dose (n = 19, 31%) and delineation (n = 17, 27%) processes. The ICR analysis showed a significant number of unacceptable variations with potential impact on tumor control and/or toxicity profile. Prospective ICRs are encouraged for future studies to prevent and correct protocol violations before start of treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Instantons and Large N

    Science.gov (United States)

    Mariño, Marcos

    2015-09-01

    Preface; Part I. Instantons: 1. Instantons in quantum mechanics; 2. Unstable vacua in quantum field theory; 3. Large order behavior and Borel summability; 4. Non-perturbative aspects of Yang-Mills theories; 5. Instantons and fermions; Part II. Large N: 6. Sigma models at large N; 7. The 1=N expansion in QCD; 8. Matrix models and matrix quantum mechanics at large N; 9. Large N QCD in two dimensions; 10. Instantons at large N; Appendix A. Harmonic analysis on S3; Appendix B. Heat kernel and zeta functions; Appendix C. Effective action for large N sigma models; References; Author index; Subject index.

  2. Large Neighborhood Search

    DEFF Research Database (Denmark)

    Pisinger, David; Røpke, Stefan

    2010-01-01

    Heuristics based on large neighborhood search have recently shown outstanding results in solving various transportation and scheduling problems. Large neighborhood search methods explore a complex neighborhood by use of heuristics. Using large neighborhoods makes it possible to find better...... candidate solutions in each iteration and hence traverse a more promising search path. Starting from the large neighborhood search method,we give an overview of very large scale neighborhood search methods and discuss recent variants and extensions like variable depth search and adaptive large neighborhood...

  3. Large scale electrolysers

    International Nuclear Information System (INIS)

    B Bello; M Junker

    2006-01-01

    Hydrogen production by water electrolysis represents nearly 4 % of the world hydrogen production. Future development of hydrogen vehicles will require large quantities of hydrogen. Installation of large scale hydrogen production plants will be needed. In this context, development of low cost large scale electrolysers that could use 'clean power' seems necessary. ALPHEA HYDROGEN, an European network and center of expertise on hydrogen and fuel cells, has performed for its members a study in 2005 to evaluate the potential of large scale electrolysers to produce hydrogen in the future. The different electrolysis technologies were compared. Then, a state of art of the electrolysis modules currently available was made. A review of the large scale electrolysis plants that have been installed in the world was also realized. The main projects related to large scale electrolysis were also listed. Economy of large scale electrolysers has been discussed. The influence of energy prices on the hydrogen production cost by large scale electrolysis was evaluated. (authors)

  4. Large Pelagics Intercept Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Intercept Survey (LPIS) is a dockside survey of private and charterboat captains who have just completed fishing trips directed at large pelagic...

  5. Large electrostatic accelerators

    International Nuclear Information System (INIS)

    Jones, C.M.

    1984-01-01

    The paper is divided into four parts: a discussion of the motivation for the construction of large electrostatic accelerators, a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year

  6. Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

    Science.gov (United States)

    Schöffski, Patrick; Sufliarsky, Jozef; Gelderblom, Hans; Blay, Jean-Yves; Strauss, Sandra J; Stacchiotti, Silvia; Rutkowski, Piotr; Lindner, Lars H; Leahy, Michael G; Italiano, Antoine; Isambert, Nicolas; Debiec-Rychter, Maria; Sciot, Raf; Van Cann, Thomas; Marréaud, Sandrine; Nzokirantevye, Axelle; Collette, Sandra; Wozniak, Agnieszka

    2018-06-01

    An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK-positive and ALK-negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK-positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK-positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved

  7. Large mass storage facility

    International Nuclear Information System (INIS)

    Peskin, A.M.

    1978-01-01

    The report of a committee to study the questions surrounding possible acquisition of a large mass-storage device is presented. The current computing environment at BNL and justification for an online large mass storage device are briefly discussed. Possible devices to meet the requirements of large mass storage are surveyed, including future devices. The future computing needs of BNL are prognosticated. 2 figures, 4 tables

  8. Large N Scalars

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2016-01-01

    We construct effective Lagrangians, and corresponding counting schemes, valid to describe the dynamics of the lowest lying large N stable massive composite state emerging in strongly coupled theories. The large N counting rules can now be employed when computing quantum corrections via an effective...

  9. Large bowel resection

    Science.gov (United States)

    ... blockage in the intestine due to scar tissue Colon cancer Diverticular disease (disease of the large bowel) Other reasons for bowel resection are: Familial polyposis (polyps are growths on the lining of the colon or rectum) Injuries that damage the large bowel ...

  10. Adaptive Large Neighbourhood Search

    DEFF Research Database (Denmark)

    Røpke, Stefan

    Large neighborhood search is a metaheuristic that has gained popularity in recent years. The heuristic repeatedly moves from solution to solution by first partially destroying the solution and then repairing it. The best solution observed during this search is presented as the final solution....... This tutorial introduces the large neighborhood search metaheuristic and the variant adaptive large neighborhood search that dynamically tunes parameters of the heuristic while it is running. Both heuristics belong to a broader class of heuristics that are searching a solution space using very large...... neighborhoods. The tutorial also present applications of the adaptive large neighborhood search, mostly related to vehicle routing problems for which the heuristic has been extremely successful. We discuss how the heuristic can be parallelized and thereby take advantage of modern desktop computers...

  11. ERP inside Large Organizations

    Directory of Open Access Journals (Sweden)

    Constantin Daniel AVRAM

    2010-01-01

    Full Text Available Many large companies in Romania are still functioning without an ERP system. Instead they are using traditional application systems built around the strong boundaries of specific functions: finance, selling, HR, production. An ERP will offer lots of advantages among which the integration of functionalities and support for top management decisions. Although the total cost of ownership is not small and there are some risks when implementing an ERP inside large and very large organizations, having such a system is mandatory. Choosing the right product and vendor and using a correct risk management strategy, will ensure a successful implementation.

  12. Large Pelagics Telephone Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Telephone Survey (LPTS) collects fishing effort information directly from captains holding Highly Migratory Species (HMS) permits (required by...

  13. Large Customers (DR Sellers)

    Energy Technology Data Exchange (ETDEWEB)

    Kiliccot, Sila [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-10-25

    State of the large customers for demand response integration of solar and wind into electric grid; openADR; CAISO; DR as a pseudo generation; commercial and industrial DR strategies; California regulations

  14. Large Pelagics Biological Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Biological Survey (LPBS) collects additional length and weight information and body parts such as otoliths, caudal vertebrae, dorsal spines, and...

  15. Large Rotor Test Apparatus

    Data.gov (United States)

    Federal Laboratory Consortium — This test apparatus, when combined with the National Full-Scale Aerodynamics Complex, produces a thorough, full-scale test capability. The Large Rotor Test Apparatus...

  16. Large transverse momentum phenomena

    International Nuclear Information System (INIS)

    Brodsky, S.J.

    1977-09-01

    It is pointed out that it is particularly significant that the quantum numbers of the leading particles are strongly correlated with the quantum numbers of the incident hadrons indicating that the valence quarks themselves are transferred to large p/sub t/. The crucial question is how they get there. Various hadron reactions are discussed covering the structure of exclusive reactions, inclusive reactions, normalization of inclusive cross sections, charge correlations, and jet production at large transverse momentum. 46 references

  17. Large Retailers’ Financial Services

    OpenAIRE

    Risso, Mario

    2010-01-01

    Over the last few years, large retailers offering financial services have considerably grown in the financial services sector. Retailers are increasing the wideness and complexity of their offer of financial services. Large retail companies provide financial services to their customers following different strategic ways. The provision of financial services in the retailers offer is implemented in several different ways related to the strategies, the structures and the degree of financial know...

  18. Large momentum transfer phenomena

    International Nuclear Information System (INIS)

    Imachi, Masahiro; Otsuki, Shoichiro; Matsuoka, Takeo; Sawada, Shoji.

    1978-01-01

    The large momentum transfer phenomena in hadron reaction drastically differ from small momentum transfer phenomena, and are described in this paper. Brief review on the features of the large transverse momentum transfer reactions is described in relation with two-body reactions, single particle productions, particle ratios, two jet structure, two particle correlations, jet production cross section, and the component of momentum perpendicular to the plane defined by the incident protons and the triggered pions and transverse momentum relative to jet axis. In case of two-body process, the exponent N of the power law of the differential cross section is a value between 10 to 11.5 in the large momentum transfer region. The breaks of the exponential behaviors into the power ones are observed at the large momentum transfer region. The break would enable to estimate the order of a critical length. The large momentum transfer phenomena strongly suggest an important role of constituents of hadrons in the hard region. Hard rearrangement of constituents from different initial hadrons induces large momentum transfer reactions. Several rules to count constituents in the hard region have been proposed so far to explain the power behavior. Scale invariant quark interaction and hard reactions are explained, and a summary of the possible types of hard subprocess is presented. (Kato, T.)

  19. Large electrostatic accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  20. Large electrostatic accelerators

    International Nuclear Information System (INIS)

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators

  1. Large field radiotherapy

    International Nuclear Information System (INIS)

    Vanasek, J.; Chvojka, Z.; Zouhar, M.

    1984-01-01

    Calculations may prove that irradiation procedures, commonly used in radiotherapy and represented by large-capacity irradiation techniques, do not exceed certain limits of integral doses with favourable radiobiological action on the organism. On the other hand integral doses in supralethal whole-body irradiation, used in the therapy of acute leukemia, represent radiobiological values which without extreme and exceptional further interventions and teamwork are not compatible with life, and the radiotherapeutist cannot use such high doses without the backing of a large team. (author)

  2. Developing Large Web Applications

    CERN Document Server

    Loudon, Kyle

    2010-01-01

    How do you create a mission-critical site that provides exceptional performance while remaining flexible, adaptable, and reliable 24/7? Written by the manager of a UI group at Yahoo!, Developing Large Web Applications offers practical steps for building rock-solid applications that remain effective even as you add features, functions, and users. You'll learn how to develop large web applications with the extreme precision required for other types of software. Avoid common coding and maintenance headaches as small websites add more pages, more code, and more programmersGet comprehensive soluti

  3. Choice of large projects

    Energy Technology Data Exchange (ETDEWEB)

    Harris, R

    1978-08-01

    Conventional cost/benefit or project analysis has generally not taken into account circumstances in which the project under consideration is large enough that its introduction to the economy would have significant general equilibrium effects. In this paper, rules are examined that would indicate whether such large projects should be accepted or rejected. The rules utilize information yielded by before-project and after-project equilibrium prices and production data. Rules are developed for the undistorted ''first-best'' case, the case in which the fixed costs of the project are covered by distortionary taxation, and for the case of projects producing public goods. 34 references.

  4. LARGE SCALE GLAZED

    DEFF Research Database (Denmark)

    Bache, Anja Margrethe

    2010-01-01

    OF SELECTED EXISTING BUILDINGS IN AND AROUND COPENHAGEN COVERED WITH MOSAIC TILES, UNGLAZED OR GLAZED CLAY TILES. ITS BUILDINGS WHICH HAVE QUALITIES THAT I WOULD LIKE APPLIED, PERHAPS TRANSFORMED OR MOST PREFERABLY, INTERPRETED ANEW, FOR THE LARGE GLAZED CONCRETE PANELS I AM DEVELOPING. KEYWORDS: COLOR, LIGHT...

  5. Large hydropower generating units

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-01

    This document presents the Brazilian experience with the design, fabrication, construction, commissioning and operation of large scale and generation capacity unities. The experience had been acquired with the implementation of Itumbiara, Paulo Afonso IV, Tucurui, Itaipu and Xingo power plants, which are among the largest world unities.

  6. Large Data Set Mining

    NARCIS (Netherlands)

    Leemans, I.B.; Broomhall, Susan

    2017-01-01

    Digital emotion research has yet to make history. Until now large data set mining has not been a very active field of research in early modern emotion studies. This is indeed surprising since first, the early modern field has such rich, copyright-free, digitized data sets and second, emotion studies

  7. Representing Large Virtual Worlds

    NARCIS (Netherlands)

    Kol, T.R.

    2018-01-01

    The ubiquity of large virtual worlds and their growing complexity in computer graphics require efficient representations. This means that we need smart solutions for the underlying storage of these complex environments, but also for their visualization. How the virtual world is best stored and how

  8. The large hadron computer

    CERN Multimedia

    Hirstius, Andreas

    2008-01-01

    Plans for dealing with the torrent of data from the Large Hadron Collider's detectors have made the CERN particle-phycis lab, yet again, a pioneer in computing as well as physics. The author describes the challenges of processing and storing data in the age of petabyt science. (4 pages)

  9. LARGE BUILDING HVAC SIMULATION

    Science.gov (United States)

    The report discusses the monitoring and collection of data relating to indoor pressures and radon concentrations under several test conditions in a large school building in Bartow, Florida. The Florida Solar Energy Center (FSEC) used an integrated computational software, FSEC 3.0...

  10. Large Hadron Collider

    CERN Multimedia

    2007-01-01

    "In the spring 2008, the Large Hadron Collider (LHC) machine at CERN (the European Particle Physics laboratory) will be switched on for the first time. The huge machine is housed in a circular tunnel, 27 km long, excavated deep under the French-Swiss border near Geneva." (1,5 page)

  11. Large reservoirs: Chapter 17

    Science.gov (United States)

    Miranda, Leandro E.; Bettoli, Phillip William

    2010-01-01

    Large impoundments, defined as those with surface area of 200 ha or greater, are relatively new aquatic ecosystems in the global landscape. They represent important economic and environmental resources that provide benefits such as flood control, hydropower generation, navigation, water supply, commercial and recreational fisheries, and various other recreational and esthetic values. Construction of large impoundments was initially driven by economic needs, and ecological consequences received little consideration. However, in recent decades environmental issues have come to the forefront. In the closing decades of the 20th century societal values began to shift, especially in the developed world. Society is no longer willing to accept environmental damage as an inevitable consequence of human development, and it is now recognized that continued environmental degradation is unsustainable. Consequently, construction of large reservoirs has virtually stopped in North America. Nevertheless, in other parts of the world construction of large reservoirs continues. The emergence of systematic reservoir management in the early 20th century was guided by concepts developed for natural lakes (Miranda 1996). However, we now recognize that reservoirs are different and that reservoirs are not independent aquatic systems inasmuch as they are connected to upstream rivers and streams, the downstream river, other reservoirs in the basin, and the watershed. Reservoir systems exhibit longitudinal patterns both within and among reservoirs. Reservoirs are typically arranged sequentially as elements of an interacting network, filter water collected throughout their watersheds, and form a mosaic of predictable patterns. Traditional approaches to fisheries management such as stocking, regulating harvest, and in-lake habitat management do not always produce desired effects in reservoirs. As a result, managers may expend resources with little benefit to either fish or fishing. Some locally

  12. Large Hadron Collider manual

    CERN Document Server

    Lavender, Gemma

    2018-01-01

    What is the universe made of? How did it start? This Manual tells the story of how physicists are seeking answers to these questions using the world’s largest particle smasher – the Large Hadron Collider – at the CERN laboratory on the Franco-Swiss border. Beginning with the first tentative steps taken to build the machine, the digestible text, supported by color photographs of the hardware involved, along with annotated schematic diagrams of the physics experiments, covers the particle accelerator’s greatest discoveries – from both the perspective of the writer and the scientists who work there. The Large Hadron Collider Manual is a full, comprehensive guide to the most famous, record-breaking physics experiment in the world, which continues to capture the public imagination as it provides new insight into the fundamental laws of nature.

  13. [Large benign prostatic hiperplasia].

    Science.gov (United States)

    Soria-Fernández, Guillermo René; Jungfermann-Guzman, José René; Lomelín-Ramos, José Pedro; Jaspersen-Gastelum, Jorge; Rosas-Nava, Jesús Emmanuel

    2012-01-01

    the term prostatic hyperplasia is most frequently used to describe the benign prostatic growth, this being a widely prevalent disorder associated with age that affects most men as they age. The association between prostate growth and urinary obstruction in older adults is well documented. large benign prostatic hyperplasia is rare and few cases have been published and should be taken into account during the study of tumors of the pelvic cavity. we report the case of an 81-year-old who had significant symptoms relating to storage and bladder emptying, with no significant elevation of prostate specific antigen. this is a rare condition but it is still important to diagnose and treat as it may be related to severe obstructive uropathy and chronic renal failure. In our institution, cases of large prostatic hyperplasia that are solved by suprapubic adenomectomy are less than 3%.

  14. [Large vessel vasculitides].

    Science.gov (United States)

    Morović-Vergles, Jadranka; Puksić, Silva; Gracanin, Ana Gudelj

    2013-01-01

    Large vessel vasculitis includes Giant cell arteritis and Takayasu arteritis. Giant cell arteritis is the most common form of vasculitis affect patients aged 50 years or over. The diagnosis should be considered in older patients who present with new onset of headache, visual disturbance, polymyalgia rheumatica and/or fever unknown cause. Glucocorticoides remain the cornerstone of therapy. Takayasu arteritis is a chronic panarteritis of the aorta ant its major branches presenting commonly in young ages. Although all large arteries can be affected, the aorta, subclavian and carotid arteries are most commonly involved. The most common symptoms included upper extremity claudication, hypertension, pain over the carotid arteries (carotidynia), dizziness and visual disturbances. Early diagnosis and treatment has improved the outcome in patients with TA.

  15. Large tandem accelerators

    International Nuclear Information System (INIS)

    Jones, C.M.

    1976-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of tandem accelerators designed to operate at maximum terminal potentials in the range 14 to 30 MV. In addition, a number of older tandem accelerators are now being significantly upgraded to improve their heavy ion performance. Both of these developments have reemphasized the importance of negative heavy ion sources. The new large tandem accelerators are described, and the requirements placed on negative heavy ion source technology by these and other tandem accelerators used for the acceleration of heavy ions are discussed. First, a brief description is given of the large tandem accelerators which have been completed recently, are under construction, or are funded for construction, second, the motivation for construction of these accelerators is discussed, and last, criteria for negative ion sources for use with these accelerators are presented

  16. Large scale reflood test

    International Nuclear Information System (INIS)

    Hirano, Kemmei; Murao, Yoshio

    1980-01-01

    The large-scale reflood test with a view to ensuring the safety of light water reactors was started in fiscal 1976 based on the special account act for power source development promotion measures by the entrustment from the Science and Technology Agency. Thereafter, to establish the safety of PWRs in loss-of-coolant accidents by joint international efforts, the Japan-West Germany-U.S. research cooperation program was started in April, 1980. Thereupon, the large-scale reflood test is now included in this program. It consists of two tests using a cylindrical core testing apparatus for examining the overall system effect and a plate core testing apparatus for testing individual effects. Each apparatus is composed of the mock-ups of pressure vessel, primary loop, containment vessel and ECCS. The testing method, the test results and the research cooperation program are described. (J.P.N.)

  17. Large scale model testing

    International Nuclear Information System (INIS)

    Brumovsky, M.; Filip, R.; Polachova, H.; Stepanek, S.

    1989-01-01

    Fracture mechanics and fatigue calculations for WWER reactor pressure vessels were checked by large scale model testing performed using large testing machine ZZ 8000 (with a maximum load of 80 MN) at the SKODA WORKS. The results are described from testing the material resistance to fracture (non-ductile). The testing included the base materials and welded joints. The rated specimen thickness was 150 mm with defects of a depth between 15 and 100 mm. The results are also presented of nozzles of 850 mm inner diameter in a scale of 1:3; static, cyclic, and dynamic tests were performed without and with surface defects (15, 30 and 45 mm deep). During cyclic tests the crack growth rate in the elastic-plastic region was also determined. (author). 6 figs., 2 tabs., 5 refs

  18. Large mass storage facility

    Energy Technology Data Exchange (ETDEWEB)

    Peskin, Arnold M.

    1978-08-01

    This is the final report of a study group organized to investigate questions surrounding the acquisition of a large mass storage facility. The programatic justification for such a system at Brookhaven is reviewed. Several candidate commercial products are identified and discussed. A draft of a procurement specification is developed. Some thoughts on possible new directions for computing at Brookhaven are also offered, although this topic was addressed outside of the context of the group's deliberations. 2 figures, 3 tables.

  19. The Large Hadron Collider

    CERN Document Server

    Juettner Fernandes, Bonnie

    2014-01-01

    What really happened during the Big Bang? Why did matter form? Why do particles have mass? To answer these questions, scientists and engineers have worked together to build the largest and most powerful particle accelerator in the world: the Large Hadron Collider. Includes glossary, websites, and bibliography for further reading. Perfect for STEM connections. Aligns to the Common Core State Standards for Language Arts. Teachers' Notes available online.

  20. Large Right Pleural Effusion

    Directory of Open Access Journals (Sweden)

    Robert Rowe

    2016-09-01

    Full Text Available History of present illness: An 83-year-old male with a distant history of tuberculosis status post treatment and resection approximately fifty years prior presented with two days of worsening shortness of breath. He denied any chest pain, and reported his shortness of breath was worse with exertion and lying flat. Significant findings: Chest x-ray and bedside ultrasound revealed a large right pleural effusion, estimated to be greater than two and a half liters in size. Discussion: The incidence of pleural effusion is estimated to be at least 1.5 million cases annually in the United States.1 Erect posteroanterior and lateral chest radiography remains the mainstay for diagnosis of a pleural effusion; on upright chest radiography small effusions (>400cc will blunt the costophrenic angles, and as the size of an effusion grows it will begin to obscure the hemidiphragm.1 Large effusions will cause mediastinal shift away from the affected side (seen in effusions >1000cc.1 Lateral decubitus chest radiography can detect effusions greater than 50cc.1 Ultrasonography can help differentiate large pulmonary masses from effusions and can be instrumental in guiding thoracentesis.1 The patient above was comfortable at rest and was admitted for a non-emergent thoracentesis. The pulmonology team removed 2500cc of fluid, and unfortunately the patient subsequently developed re-expansion pulmonary edema and pneumothorax ex-vacuo. It is generally recommended that no more than 1500cc be removed to minimize the risk of re-expansion pulmonary edema.2

  1. Large litter sizes

    DEFF Research Database (Denmark)

    Sandøe, Peter; Rutherford, K.M.D.; Berg, Peer

    2012-01-01

    This paper presents some key results and conclusions from a review (Rutherford et al. 2011) undertaken regarding the ethical and welfare implications of breeding for large litter size in the domestic pig and about different ways of dealing with these implications. Focus is primarily on the direct...... possible to achieve a drop in relative piglet mortality and the related welfare problems. However, there will be a growing problem with the need to use foster or nurse sows which may have negative effects on both sows and piglets. This gives rise to new challenges for management....

  2. Large lithium loop experience

    International Nuclear Information System (INIS)

    Kolowith, R.; Owen, T.J.; Berg, J.D.; Atwood, J.M.

    1981-10-01

    An engineering design and operating experience of a large, isothermal, lithium-coolant test loop are presented. This liquid metal coolant loop is called the Experimental Lithium System (ELS) and has operated safely and reliably for over 6500 hours through September 1981. The loop is used for full-scale testing of components for the Fusion Materials Irradiation Test (FMIT) Facility. Main system parameters include coolant temperatures to 430 0 C and flow to 0.038 m 3 /s (600 gal/min). Performance of the main pump, vacuum system, and control system is discussed. Unique test capabilities of the ELS are also discussed

  3. Large coil test facility

    International Nuclear Information System (INIS)

    Nelms, L.W.; Thompson, P.B.

    1980-01-01

    Final design of the facility is nearing completion, and 20% of the construction has been accomplished. A large vacuum chamber, houses the test assembly which is coupled to appropriate cryogenic, electrical, instrumentation, diagnostc systems. Adequate assembly/disassembly areas, shop space, test control center, offices, and test support laboratories are located in the same building. Assembly and installation operations are accomplished with an overhead crane. The major subsystems are the vacuum system, the test stand assembly, the cryogenic system, the experimental electric power system, the instrumentation and control system, and the data aquisition system

  4. Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH.

    Science.gov (United States)

    Rianthavorn, Pornpimol; Cain, Joan P; Turman, Martin A

    2008-08-01

    The available treatment options for hyponatremia secondary to SIADH are limited and not completely effective. Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients. However, data on efficacy and safety of conivaptan in pediatrics are limited. We report a case of a 13-year-old boy with extensively metastasized anaplastic large-cell lymphoma. He also developed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) prior to chemotherapy initiation. SIADH management in this case was complicated when fluid restriction was not safely attainable. Conivaptan played a significant role in this situation by allowing provision of a large amount of intravenous fluid prior to and during induction chemotherapy. It proved to be an important component in preventing uric acid nephropathy/tumor lysis syndrome. Conivaptan induced free-water clearance as indicated by increased urine output and decreased urine osmolality. The patient responded to conivaptan without any adverse effects.

  5. Large orbit neoclassical transport

    International Nuclear Information System (INIS)

    Lin, Z.; Tang, W.M.; Lee, W.W.

    1997-01-01

    Neoclassical transport in the presence of large ion orbits is investigated. The study is motivated by the recent experimental results that ion thermal transport levels in enhanced confinement tokamak plasmas fall below the open-quotes irreducible minimum levelclose quotes predicted by standard neoclassical theory. This apparent contradiction is resolved in the present analysis by relaxing the basic neoclassical assumption that the ions orbital excursions are much smaller than the local toroidal minor radius and the equilibrium scale lengths of the system. Analytical and simulation results are in agreement with trends from experiments. The development of a general formalism for neoclassical transport theory with finite orbit width is also discussed. copyright 1997 American Institute of Physics

  6. Large Superconducting Magnet Systems

    CERN Document Server

    Védrine, P.

    2014-07-17

    The increase of energy in accelerators over the past decades has led to the design of superconducting magnets for both accelerators and the associated detectors. The use of Nb−Ti superconducting materials allows an increase in the dipole field by up to 10 T compared with the maximum field of 2 T in a conventional magnet. The field bending of the particles in the detectors and generated by the magnets can also be increased. New materials, such as Nb$_{3}$Sn and high temperature superconductor (HTS) conductors, can open the way to higher fields, in the range 13–20 T. The latest generations of fusion machines producing hot plasma also use large superconducting magnet systems.

  7. Large Scale Solar Heating

    DEFF Research Database (Denmark)

    Heller, Alfred

    2001-01-01

    The main objective of the research was to evaluate large-scale solar heating connected to district heating (CSDHP), to build up a simulation tool and to demonstrate the application of the simulation tool for design studies and on a local energy planning case. The evaluation was mainly carried out...... model is designed and validated on the Marstal case. Applying the Danish Reference Year, a design tool is presented. The simulation tool is used for proposals for application of alternative designs, including high-performance solar collector types (trough solar collectors, vaccum pipe collectors......). Simulation programs are proposed as control supporting tool for daily operation and performance prediction of central solar heating plants. Finaly the CSHP technolgy is put into persepctive with respect to alternatives and a short discussion on the barries and breakthrough of the technology are given....

  8. Large Superconducting Magnet Systems

    Energy Technology Data Exchange (ETDEWEB)

    Védrine, P [Saclay (France)

    2014-07-01

    The increase of energy in accelerators over the past decades has led to the design of superconducting magnets for both accelerators and the associated detectors. The use of Nb−Ti superconducting materials allows an increase in the dipole field by up to 10 T compared with the maximum field of 2 T in a conventional magnet. The field bending of the particles in the detectors and generated by the magnets can also be increased. New materials, such as Nb3Sn and high temperature superconductor (HTS) conductors, can open the way to higher fields, in the range 13–20 T. The latest generations of fusion machines producing hot plasma also use large superconducting magnet systems.

  9. Large forging manufacturing process

    Science.gov (United States)

    Thamboo, Samuel V.; Yang, Ling

    2002-01-01

    A process for forging large components of Alloy 718 material so that the components do not exhibit abnormal grain growth includes the steps of: a) providing a billet with an average grain size between ASTM 0 and ASTM 3; b) heating the billet to a temperature of between 1750.degree. F. and 1800.degree. F.; c) upsetting the billet to obtain a component part with a minimum strain of 0.125 in at least selected areas of the part; d) reheating the component part to a temperature between 1750.degree. F. and 1800.degree. F.; e) upsetting the component part to a final configuration such that said selected areas receive no strains between 0.01 and 0.125; f) solution treating the component part at a temperature of between 1725.degree. F. and 1750.degree. F.; and g) aging the component part over predetermined times at different temperatures. A modified process achieves abnormal grain growth in selected areas of a component where desirable.

  10. Large scale tracking algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Ross L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Love, Joshua Alan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Melgaard, David Kennett [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Karelitz, David B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pitts, Todd Alan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Zollweg, Joshua David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Anderson, Dylan Z. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nandy, Prabal [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Whitlow, Gary L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bender, Daniel A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Byrne, Raymond Harry [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    Low signal-to-noise data processing algorithms for improved detection, tracking, discrimination and situational threat assessment are a key research challenge. As sensor technologies progress, the number of pixels will increase signi cantly. This will result in increased resolution, which could improve object discrimination, but unfortunately, will also result in a significant increase in the number of potential targets to track. Many tracking techniques, like multi-hypothesis trackers, suffer from a combinatorial explosion as the number of potential targets increase. As the resolution increases, the phenomenology applied towards detection algorithms also changes. For low resolution sensors, "blob" tracking is the norm. For higher resolution data, additional information may be employed in the detection and classfication steps. The most challenging scenarios are those where the targets cannot be fully resolved, yet must be tracked and distinguished for neighboring closely spaced objects. Tracking vehicles in an urban environment is an example of such a challenging scenario. This report evaluates several potential tracking algorithms for large-scale tracking in an urban environment.

  11. The large binocular telescope.

    Science.gov (United States)

    Hill, John M

    2010-06-01

    The Large Binocular Telescope (LBT) Observatory is a collaboration among institutions in Arizona, Germany, Italy, Indiana, Minnesota, Ohio, and Virginia. The telescope on Mount Graham in Southeastern Arizona uses two 8.4 m diameter primary mirrors mounted side by side. A unique feature of the LBT is that the light from the two Gregorian telescope sides can be combined to produce phased-array imaging of an extended field. This cophased imaging along with adaptive optics gives the telescope the diffraction-limited resolution of a 22.65 m aperture and a collecting area equivalent to an 11.8 m circular aperture. This paper describes the design, construction, and commissioning of this unique telescope. We report some sample astronomical results with the prime focus cameras. We comment on some of the technical challenges and solutions. The telescope uses two F/15 adaptive secondaries to correct atmospheric turbulence. The first of these adaptive mirrors has completed final system testing in Firenze, Italy, and is planned to be at the telescope by Spring 2010.

  12. Large Format Radiographic Imaging

    International Nuclear Information System (INIS)

    Rohrer, J. S.; Stewart, Lacey; Wilke, M. D.; King, N. S.; Baker A, S.; Lewis, Wilfred

    1999-01-01

    Radiographic imaging continues to be a key diagnostic in many areas at Los Alamos National Laboratory (LANL). Radiographic recording systems have taken on many form, from high repetition-rate, gated systems to film recording and storage phosphors. Some systems are designed for synchronization to an accelerator while others may be single shot or may record a frame sequence in a dynamic radiography experiment. While film recording remains a reliable standby in the radiographic community, there is growing interest in investigating electronic recording for many applications. The advantages of real time access to remote data acquisition are highly attractive. Cooled CCD camera systems are capable of providing greater sensitivity with improved signal-to-noise ratio. This paper begins with a review of performance characteristics of the Bechtel Nevada large format imaging system, a gated system capable of viewing scintillators up to 300 mm in diameter. We then examine configuration alternatives in lens coupled and fiber optically coupled electro-optical recording systems. Areas of investigation include tradeoffs between fiber optic and lens coupling, methods of image magnification, and spectral matching from scintillator to CCD camera. Key performance features discussed include field of view, resolution, sensitivity, dynamic range, and system noise characteristics

  13. Large Ventral Hernia

    Directory of Open Access Journals (Sweden)

    Meryl Abrams, MD

    2018-04-01

    Full Text Available History of present illness: A 46-year-old female presented to the emergency department (ED with diffuse abdominal pain and three days of poor oral intake associated with non-bilious, non-bloody vomiting. Initial vital signs consisted of a mild resting tachycardia of 111 with a temperature of 38.0 degrees Celsius (°C. On examination, the patient had a large pannus extending to the knees, which contained a hernia. She was tender in this region on examination. Laboratory values included normal serum chemistries and mild leukocytosis of 12.2. The patient reports that her abdomen had been enlarging over the previous 8 years but had not been painful until 3 days prior to presentation. The patient had no associated fever, chills, diarrhea, constipation, chest pain or shortness of breath. Significant findings: Computed tomography (CT scan with intravenous (IV contrast of the abdomen and pelvis demonstrated a large pannus containing a ventral hernia with abdominal contents extending below the knees (white circle, elongation of mesenteric vessels to accommodate abdominal contents outside of the abdomen (white arrow and air fluid levels (white arrow indicating a small bowel obstruction. Discussion: Hernias are a common chief complaint seen in the emergency department. The estimated lifetime risk of a spontaneous abdominal hernia is 5%.1 The most common type of hernia is inguinal while the next most common type of hernia is femoral, which are more common in women.1 Ventral hernias can be epigastric, incisional, or primary abdominal. An asymptomatic, reducible hernia can be followed up as outpatient with a general surgeon for elective repair.2 Hernias become problematic when they are either incarcerated or strangulated. A hernia is incarcerated when the hernia is irreducible and strangulated when its blood supply is compromised. A complicated hernia, especially strangulated, can have a mortality of greater than 50%.1 It is key to perform a thorough history

  14. Unification, small and large

    Energy Technology Data Exchange (ETDEWEB)

    Fritzsch, Harald

    1993-04-15

    Full text: Fruitful exchanges between particle physics, astrophysics and cosmology have become a common feature in the last decade. In January, Coral Gables near Miami was the stage for a 'Unified Symmetry in the Small and the Large' meeting. Coral Gables is a famous physics venue. In January 1964, the year that the quark model of hadrons emerged, Behram Kursunoglu initiated a series of particle physics meetings that continued for 20 years and formed a regular focus for this development. The final such meeting was in 1983, coinciding with both the 80th birthday of field theory pioneer Paul Dirac, who worked in Florida towards the end of his career, and the discovery of the W bosons at CERN. The resurrected Coral Gables meeting began with historical accounts of the emergence of Big Bang cosmology, by Robert Ralph and Herman Alpher, while Andrei Linde proposed our expanding universe as a small part of a stationary system, infinite both in space and in time. The observational status of Big Bang cosmology was reviewed by Bruce Partridge, John Mather and Martin Harwit, emphasizing the cosmic background radiation, where temperature is now measured by the COBE satellite detectors to 2.726 ± 0.01 OK. The tiny fluctuations observed by COBE pose problems for standard cold dark matter models. Edward ('Rocky') Kolb reported on new studies on the electroweak phase transition, based on an analogy with the physics of liquid crystals. Richard Holman discussed the fate of global symmetries at energies near the Planck (grand unification) energy, and Paul Steinhardt talked about tensorial and scalar metric fluctuations in the light of the COBE results. Anthony Tyson gave an impressive description of dark matter studies using gravitational lensing, now emerging as a unique tool for indirectly observing intervening dark matter. A neutrino mass of 10 electronvolts could account for observed dark matter distributions, but fails to provide the necessary seeds for galaxy formation. A

  15. Unification, small and large

    International Nuclear Information System (INIS)

    Fritzsch, Harald

    1993-01-01

    Full text: Fruitful exchanges between particle physics, astrophysics and cosmology have become a common feature in the last decade. In January, Coral Gables near Miami was the stage for a 'Unified Symmetry in the Small and the Large' meeting. Coral Gables is a famous physics venue. In January 1964, the year that the quark model of hadrons emerged, Behram Kursunoglu initiated a series of particle physics meetings that continued for 20 years and formed a regular focus for this development. The final such meeting was in 1983, coinciding with both the 80th birthday of field theory pioneer Paul Dirac, who worked in Florida towards the end of his career, and the discovery of the W bosons at CERN. The resurrected Coral Gables meeting began with historical accounts of the emergence of Big Bang cosmology, by Robert Ralph and Herman Alpher, while Andrei Linde proposed our expanding universe as a small part of a stationary system, infinite both in space and in time. The observational status of Big Bang cosmology was reviewed by Bruce Partridge, John Mather and Martin Harwit, emphasizing the cosmic background radiation, where temperature is now measured by the COBE satellite detectors to 2.726 ± 0.01 OK. The tiny fluctuations observed by COBE pose problems for standard cold dark matter models. Edward ('Rocky') Kolb reported on new studies on the electroweak phase transition, based on an analogy with the physics of liquid crystals. Richard Holman discussed the fate of global symmetries at energies near the Planck (grand unification) energy, and Paul Steinhardt talked about tensorial and scalar metric fluctuations in the light of the COBE results. Anthony Tyson gave an impressive description of dark matter studies using gravitational lensing, now emerging as a unique tool for indirectly observing intervening dark matter. A neutrino mass of 10 electronvolts could account for observed dark matter distributions, but fails to provide the necessary seeds for

  16. Laboratory for Large Data Research

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: The Laboratory for Large Data Research (LDR) addresses a critical need to rapidly prototype shared, unified access to large amounts of data across both the...

  17. Large-D gravity and low-D strings.

    Science.gov (United States)

    Emparan, Roberto; Grumiller, Daniel; Tanabe, Kentaro

    2013-06-21

    We show that in the limit of a large number of dimensions a wide class of nonextremal neutral black holes has a universal near-horizon limit. The limiting geometry is the two-dimensional black hole of string theory with a two-dimensional target space. Its conformal symmetry explains the properties of massless scalars found recently in the large-D limit. For black branes with string charges, the near-horizon geometry is that of the three-dimensional black strings of Horne and Horowitz. The analogies between the α' expansion in string theory and the large-D expansion in gravity suggest a possible effective string description of the large-D limit of black holes. We comment on applications to several subjects, in particular to the problem of critical collapse.

  18. Quenches in large superconducting magnets

    International Nuclear Information System (INIS)

    Eberhard, P.H.; Alston-Garnjost, M.; Green, M.A.; Lecomte, P.; Smits, R.G.; Taylor, J.D.; Vuillemin, V.

    1977-08-01

    The development of large high current density superconducting magnets requires an understanding of the quench process by which the magnet goes normal. A theory which describes the quench process in large superconducting magnets is presented and compared with experimental measurements. The use of a quench theory to improve the design of large high current density superconducting magnets is discussed

  19. Health impacts of large dams

    International Nuclear Information System (INIS)

    Lerer, L.B.

    1999-01-01

    Large dams have been criticized because of their negative environmental and social impacts. Public health interest largely has focused on vector-borne diseases, such as schistosomiasis, associated with reservoirs and irrigation projects. Large dams also influence health through changes in water and food security, increases in communicable diseases, and the social disruption caused by construction and involuntary resettlement. Communities living in close proximity to large dams often do not benefit from water transfer and electricity generation revenues. A comprehensive health component is required in environmental and social impact assessments for large dam projects

  20. Large deviations and idempotent probability

    CERN Document Server

    Puhalskii, Anatolii

    2001-01-01

    In the view of many probabilists, author Anatolii Puhalskii''s research results stand among the most significant achievements in the modern theory of large deviations. In fact, his work marked a turning point in the depth of our understanding of the connections between the large deviation principle (LDP) and well-known methods for establishing weak convergence results.Large Deviations and Idempotent Probability expounds upon the recent methodology of building large deviation theory along the lines of weak convergence theory. The author develops an idempotent (or maxitive) probability theory, introduces idempotent analogues of martingales (maxingales), Wiener and Poisson processes, and Ito differential equations, and studies their properties. The large deviation principle for stochastic processes is formulated as a certain type of convergence of stochastic processes to idempotent processes. The author calls this large deviation convergence.The approach to establishing large deviation convergence uses novel com...

  1. Large-scale grid management

    International Nuclear Information System (INIS)

    Langdal, Bjoern Inge; Eggen, Arnt Ove

    2003-01-01

    The network companies in the Norwegian electricity industry now have to establish a large-scale network management, a concept essentially characterized by (1) broader focus (Broad Band, Multi Utility,...) and (2) bigger units with large networks and more customers. Research done by SINTEF Energy Research shows so far that the approaches within large-scale network management may be structured according to three main challenges: centralization, decentralization and out sourcing. The article is part of a planned series

  2. Large-scale solar purchasing

    International Nuclear Information System (INIS)

    1999-01-01

    The principal objective of the project was to participate in the definition of a new IEA task concerning solar procurement (''the Task'') and to assess whether involvement in the task would be in the interest of the UK active solar heating industry. The project also aimed to assess the importance of large scale solar purchasing to UK active solar heating market development and to evaluate the level of interest in large scale solar purchasing amongst potential large scale purchasers (in particular housing associations and housing developers). A further aim of the project was to consider means of stimulating large scale active solar heating purchasing activity within the UK. (author)

  3. Physics with large extra dimensions

    Indian Academy of Sciences (India)

    can then be accounted by the existence of large internal dimensions, in the sub- ... strongly coupled heterotic theory with one large dimension is described by a weakly ..... one additional U(1) factor corresponding to an extra 'U(1)' D-brane is ...

  4. MPQS with three large primes

    NARCIS (Netherlands)

    Leyland, P.; Lenstra, A.K.; Dodson, B.; Muffett, A.; Wagstaff, S.; Fieker, C.; Kohel, D.R.

    2002-01-01

    We report the factorization of a 135-digit integer by the triple-large-prime variation of the multiple polynomial quadratic sieve. Previous workers [6][10] had suggested that using more than two large primes would be counterproductive, because of the greatly increased number of false reports from

  5. Querying Large Biological Network Datasets

    Science.gov (United States)

    Gulsoy, Gunhan

    2013-01-01

    New experimental methods has resulted in increasing amount of genetic interaction data to be generated every day. Biological networks are used to store genetic interaction data gathered. Increasing amount of data available requires fast large scale analysis methods. Therefore, we address the problem of querying large biological network datasets.…

  6. Large-scale data analytics

    CERN Document Server

    Gkoulalas-Divanis, Aris

    2014-01-01

    Provides cutting-edge research in large-scale data analytics from diverse scientific areas Surveys varied subject areas and reports on individual results of research in the field Shares many tips and insights into large-scale data analytics from authors and editors with long-term experience and specialization in the field

  7. Mobility and powering of large detectors. Moving large detectors

    International Nuclear Information System (INIS)

    Thompson, J.

    1977-01-01

    The possibility is considered of moving large lepton detectors at ISABELLE for readying new experiments, detector modifications, and detector repair. A large annex (approximately 25 m x 25 m) would be built adjacent to the Lepton Hall separated from the Lepton Hall by a wall of concrete 11 m high x 12 m wide (for clearance of the detector) and approximately 3 m thick (for radiation shielding). A large pad would support the detector, the door, the cryogenic support system and the counting house. In removing the detector from the beam hall, one would push the pad into the annex, add a dummy beam pipe, bake out the beam pipe, and restack and position the wall on a small pad at the door. The beam could then operate again while experimenters could work on the large detector in the annex. A consideration and rough price estimate of various questions and proposed solutions are given

  8. Measuring happiness in large population

    Science.gov (United States)

    Wenas, Annabelle; Sjahputri, Smita; Takwin, Bagus; Primaldhi, Alfindra; Muhamad, Roby

    2016-01-01

    The ability to know emotional states for large number of people is important, for example, to ensure the effectiveness of public policies. In this study, we propose a measure of happiness that can be used in large scale population that is based on the analysis of Indonesian language lexicons. Here, we incorporate human assessment of Indonesian words, then quantify happiness on large-scale of texts gathered from twitter conversations. We used two psychological constructs to measure happiness: valence and arousal. We found that Indonesian words have tendency towards positive emotions. We also identified several happiness patterns during days of the week, hours of the day, and selected conversation topics.

  9. Large Hadron Collider nears completion

    CERN Multimedia

    2008-01-01

    Installation of the final component of the Large Hadron Collider particle accelerator is under way along the Franco-Swiss border near Geneva, Switzerland. When completed this summer, the LHC will be the world's largest and most complex scientific instrument.

  10. Phenomenology of large Nc QCD

    International Nuclear Information System (INIS)

    Lebed, R.F.

    1999-01-01

    These lectures are designed to introduce the methods and results of large N c QCD in a presentation intended for nuclear and particle physicists alike. Beginning with definitions and motivations of the approach, we demonstrate that all quark and gluon Feynman diagrams are organized into classes based on powers of 1/N c . We then show that this result can be translated into definite statements about mesons and baryons containing arbitrary numbers of constituents. In the mesons, numerous well-known phenomenological properties follow as immediate consequences of simply counting powers of N c , while for the baryons, quantitative large N c analyses of masses and other properties are seen to agree with experiment, even when 'large' N c is set equal to its observed value of 3. Large N c reasoning is also used to explain some simple features of nuclear interactions. (author)

  11. Phenomenology of large Nc QCD

    International Nuclear Information System (INIS)

    Richard Lebed

    1998-01-01

    These lectures are designed to introduce the methods and results of large N c QCD in a presentation intended for nuclear and particle physicists alike. Beginning with definitions and motivations of the approach, they demonstrate that all quark and gluon Feynman diagrams are organized into classes based on powers of 1/N c . They then show that this result can be translated into definite statements about mesons and baryons containing arbitrary numbers of constituents. In the mesons, numerous well-known phenomenological properties follow as immediate consequences of simply counting powers of N c , while for the baryons, quantitative large N c analyses of masses and other properties are seen to agree with experiment, even when ''large'' N c is set equal to its observed value of 3. Large N c reasoning is also used to explain some simple features of nuclear interactions

  12. Community Detection for Large Graphs

    KAUST Repository

    Peng, Chengbin; Kolda, Tamara G.; Pinar, Ali; Zhang, Zhihua; Keyes, David E.

    2014-01-01

    Many real world networks have inherent community structures, including social networks, transportation networks, biological networks, etc. For large scale networks with millions or billions of nodes in real-world applications, accelerating current

  13. Physics with large extra dimensions

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 62; Issue 2 ... The recent understanding of string theory opens the possibility that the string scale can be as ... by the existence of large internal dimensions, in the sub-millimeter region.

  14. Utility unbundling : large consumer's perspective

    International Nuclear Information System (INIS)

    Block, C.

    1997-01-01

    The perspectives of Sunoco as a large user of electric power on utility unbundling were presented. Sunoco's Sarnia refinery runs up an energy bill of over $60 million per year for electricity, natural gas (used both as a feedstock as well as a fuel), natural gas liquids and steam. As a large customer Sunoco advocates unbundling of all services, leaving only the 'pipes and wires' as true monopolies. In their view, regulation distorts the market place and prevents the lower prices that would result from competition as has been seen in the airline and telephone industries. Sunoco's expectation is that in the post-deregulated environment large and small consumers will have a choice of energy supplier, and large consumers will increasingly turn to co-generation as the most desirable way of meeting their power needs

  15. LSD: Large Survey Database framework

    Science.gov (United States)

    Juric, Mario

    2012-09-01

    The Large Survey Database (LSD) is a Python framework and DBMS for distributed storage, cross-matching and querying of large survey catalogs (>10^9 rows, >1 TB). The primary driver behind its development is the analysis of Pan-STARRS PS1 data. It is specifically optimized for fast queries and parallel sweeps of positionally and temporally indexed datasets. It transparently scales to more than >10^2 nodes, and can be made to function in "shared nothing" architectures.

  16. Large-scale solar heat

    Energy Technology Data Exchange (ETDEWEB)

    Tolonen, J.; Konttinen, P.; Lund, P. [Helsinki Univ. of Technology, Otaniemi (Finland). Dept. of Engineering Physics and Mathematics

    1998-12-31

    In this project a large domestic solar heating system was built and a solar district heating system was modelled and simulated. Objectives were to improve the performance and reduce costs of a large-scale solar heating system. As a result of the project the benefit/cost ratio can be increased by 40 % through dimensioning and optimising the system at the designing stage. (orig.)

  17. Optimization theory for large systems

    CERN Document Server

    Lasdon, Leon S

    2002-01-01

    Important text examines most significant algorithms for optimizing large systems and clarifying relations between optimization procedures. Much data appear as charts and graphs and will be highly valuable to readers in selecting a method and estimating computer time and cost in problem-solving. Initial chapter on linear and nonlinear programming presents all necessary background for subjects covered in rest of book. Second chapter illustrates how large-scale mathematical programs arise from real-world problems. Appendixes. List of Symbols.

  18. Hidden supersymmetry and large N

    International Nuclear Information System (INIS)

    Alfaro, J.

    1988-01-01

    In this paper we present a new method to deal with the leading order in the large-N expansion of a quantum field theory. The method uses explicitly the hidden supersymmetry that is present in the path-integral formulation of a stochastic process. In addition to this we derive a new relation that is valid in the leading order of the large-N expansion of the hermitian-matrix model for any spacetime dimension. (orig.)

  19. Large transverse momentum hadronic processes

    International Nuclear Information System (INIS)

    Darriulat, P.

    1977-01-01

    The possible relations between deep inelastic leptoproduction and large transverse momentum (psub(t)) processes in hadronic collisions are usually considered in the framework of the quark-parton picture. Experiments observing the structure of the final state in proton-proton collisions producing at least one large transverse momentum particle have led to the following conclusions: a large fraction of produced particles are uneffected by the large psub(t) process. The other products are correlated to the large psub(t) particle. Depending upon the sign of scalar product they can be separated into two groups of ''towards-movers'' and ''away-movers''. The experimental evidence are reviewed favouring such a picture and the properties are discussed of each of three groups (underlying normal event, towards-movers and away-movers). Some phenomenological interpretations are presented. The exact nature of away- and towards-movers must be further investigated. Their apparent jet structure has to be confirmed. Angular correlations between leading away and towards movers are very informative. Quantum number flow, both within the set of away and towards-movers, and between it and the underlying normal event, are predicted to behave very differently in different models

  20. The large-s field-reversed configuration experiment

    International Nuclear Information System (INIS)

    Hoffman, A.L.; Carey, L.N.; Crawford, E.A.; Harding, D.G.; DeHart, T.E.; McDonald, K.F.; McNeil, J.L.; Milroy, R.D.; Slough, J.T.; Maqueda, R.; Wurden, G.A.

    1993-01-01

    The Large-s Experiment (LSX) was built to study the formation and equilibrium properties of field-reversed configurations (FRCs) as the scale size increases. The dynamic, field-reversed theta-pinch method of FRC creation produces axial and azimuthal deformations and makes formation difficult, especially in large devices with large s (number of internal gyroradii) where it is difficult to achieve initial plasma uniformity. However, with the proper technique, these formation distortions can be minimized and are then observed to decay with time. This suggests that the basic stability and robustness of FRCs formed, and in some cases translated, in smaller devices may also characterize larger FRCs. Elaborate formation controls were included on LSX to provide the initial uniformity and symmetry necessary to minimize formation disturbances, and stable FRCs could be formed up to the design goal of s = 8. For x ≤ 4, the formation distortions decayed away completely, resulting in symmetric equilibrium FRCs with record confinement times up to 0.5 ms, agreeing with previous empirical scaling laws (τ∝sR). Above s = 4, reasonably long-lived (up to 0.3 ms) configurations could still be formed, but the initial formation distortions were so large that they never completely decayed away, and the equilibrium confinement was degraded from the empirical expectations. The LSX was only operational for 1 yr, and it is not known whether s = 4 represents a fundamental limit for good confinement in simple (no ion beam stabilization) FRCs or whether it simply reflects a limit of present formation technology. Ideally, s could be increased through flux buildup from neutral beams. Since the addition of kinetic or beam ions will probably be desirable for heating, sustainment, and further stabilization of magnetohydrodynamic modes at reactor-level s values, neutral beam injection is the next logical step in FRC development. 24 refs., 21 figs., 2 tabs

  1. Large aperture optical switching devices

    International Nuclear Information System (INIS)

    Goldhar, J.; Henesian, M.A.

    1983-01-01

    We have developed a new approach to constructing large aperture optical switches for next generation inertial confinement fusion lasers. A transparent plasma electrode formed in low pressure ionized gas acts as a conductive coating to allow the uniform charging of the optical faces of an electro-optic material. In this manner large electric fields can be applied longitudinally to large aperture, high aspect ratio Pockels cells. We propose a four-electrode geometry to create the necessary high conductivity plasma sheets, and have demonstrated fast (less than 10 nsec) switching in a 5x5 cm aperture KD*P Pockels cell with such a design. Detaid modelling of Pockels cell performance with plasma electrodes has been carried out for 15 and 30 cm aperture designs

  2. Assembling large, complex environmental metagenomes

    Energy Technology Data Exchange (ETDEWEB)

    Howe, A. C. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Plant Soil and Microbial Sciences; Jansson, J. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Earth Sciences Division; Malfatti, S. A. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Tringe, S. G. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Tiedje, J. M. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Plant Soil and Microbial Sciences; Brown, C. T. [Michigan State Univ., East Lansing, MI (United States). Microbiology and Molecular Genetics, Computer Science and Engineering

    2012-12-28

    The large volumes of sequencing data required to sample complex environments deeply pose new challenges to sequence analysis approaches. De novo metagenomic assembly effectively reduces the total amount of data to be analyzed but requires significant computational resources. We apply two pre-assembly filtering approaches, digital normalization and partitioning, to make large metagenome assemblies more computationaly tractable. Using a human gut mock community dataset, we demonstrate that these methods result in assemblies nearly identical to assemblies from unprocessed data. We then assemble two large soil metagenomes from matched Iowa corn and native prairie soils. The predicted functional content and phylogenetic origin of the assembled contigs indicate significant taxonomic differences despite similar function. The assembly strategies presented are generic and can be extended to any metagenome; full source code is freely available under a BSD license.

  3. Large scale structure and baryogenesis

    International Nuclear Information System (INIS)

    Kirilova, D.P.; Chizhov, M.V.

    2001-08-01

    We discuss a possible connection between the large scale structure formation and the baryogenesis in the universe. An update review of the observational indications for the presence of a very large scale 120h -1 Mpc in the distribution of the visible matter of the universe is provided. The possibility to generate a periodic distribution with the characteristic scale 120h -1 Mpc through a mechanism producing quasi-periodic baryon density perturbations during inflationary stage, is discussed. The evolution of the baryon charge density distribution is explored in the framework of a low temperature boson condensate baryogenesis scenario. Both the observed very large scale of a the visible matter distribution in the universe and the observed baryon asymmetry value could naturally appear as a result of the evolution of a complex scalar field condensate, formed at the inflationary stage. Moreover, for some model's parameters a natural separation of matter superclusters from antimatter ones can be achieved. (author)

  4. Large ceramics for fusion applications

    International Nuclear Information System (INIS)

    Hauth, W.E.; Stoddard, S.D.

    1979-01-01

    Prominent ceramic raw materials and products manufacturers were surveyed to determine the state of the art for alumina ceramic fabrication. This survey emphasized current capabilities and limitations for fabrication of large, high-density, high-purity, complex shapes. Some directions are suggested for future needs and development. Ceramic-to-ceramic sealing has applications for several technologies that require large and/or complex vacuum-tight ceramic shapes. Information is provided concerning the assembly of complex monolithic ceramic shapes by bonding of subassemblies at temperatures ranging from 450 to 1500 0 C. Future applications and fabrication techniques for various materials are presented

  5. Dijets at large rapidity intervals

    CERN Document Server

    Pope, B G

    2001-01-01

    Inclusive diet production at large pseudorapidity intervals ( Delta eta ) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large Delta eta in pp collisions at square root s = 1800 and 630 GeV using the DOE detector. The partonic cross section increases strongly with the size of Delta eta . The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of alpha /sub BFKL/(20 GeV) = 1.65 +or- 0.07.

  6. Anaplastic ependymoma of the fourth ventricle causing obstrictive ...

    African Journals Online (AJOL)

    An initial insertion of a ventriculo-peritoneal shunt (V-P) to deal with the acute intracranial hypertension was done. Subsequently, sub-occipital craniectomy and sub-total resection of the tumour were performed successfully. Post-operative radiotherapy was also undertaken on the patient. The pertinent literature is reviewed.

  7. Large Eddy Simulation of turbulence

    International Nuclear Information System (INIS)

    Poullet, P.; Sancandi, M.

    1994-12-01

    Results of Large Eddy Simulation of 3D isotropic homogeneous turbulent flows are presented. A computer code developed on Connexion Machine (CM5) has allowed to compare two turbulent viscosity models (Smagorinsky and structure function). The numerical scheme influence on the energy density spectrum is also studied [fr

  8. The Large Vector Multiplet Action

    OpenAIRE

    Ryb, Itai

    2007-01-01

    We discuss possible actions for the d=2, N=(2,2) large vector multiplet that gauges isometries of generalized Kahler geometries. We explore two scenarios that allow us to write kinetic and superpotential terms for the scalar field-strengths, and write kinetic terms for the spinor invariants that can introduce topological terms for the connections.

  9. Qatar - large capital investment planned

    International Nuclear Information System (INIS)

    Roberts, J.

    1996-01-01

    Large capital investments are planned throughout Qatar's energy industry over the next five years totalling $25 billion. This article describes the successful commissioning of Qatar's first liquefied natural gas (LNG) project on time and within budget. The second LNG plant is well underway and plans for a third are under negotiation. (UK)

  10. Large deviations and portfolio optimization

    Science.gov (United States)

    Sornette, Didier

    Risk control and optimal diversification constitute a major focus in the finance and insurance industries as well as, more or less consciously, in our everyday life. We present a discussion of the characterization of risks and of the optimization of portfolios that starts from a simple illustrative model and ends by a general functional integral formulation. A major item is that risk, usually thought of as one-dimensional in the conventional mean-variance approach, has to be addressed by the full distribution of losses. Furthermore, the time-horizon of the investment is shown to play a major role. We show the importance of accounting for large fluctuations and use the theory of Cramér for large deviations in this context. We first treat a simple model with a single risky asset that exemplifies the distinction between the average return and the typical return and the role of large deviations in multiplicative processes, and the different optimal strategies for the investors depending on their size. We then analyze the case of assets whose price variations are distributed according to exponential laws, a situation that is found to describe daily price variations reasonably well. Several portfolio optimization strategies are presented that aim at controlling large risks. We end by extending the standard mean-variance portfolio optimization theory, first within the quasi-Gaussian approximation and then using a general formulation for non-Gaussian correlated assets in terms of the formalism of functional integrals developed in the field theory of critical phenomena.

  11. Inconsistency in large pharmacogenomic studies

    DEFF Research Database (Denmark)

    Haibe-Kains, Benjamin; El-Hachem, Nehme; Birkbak, Nicolai Juul

    2013-01-01

    Two large-scale pharmacogenomic studies were published recently in this journal. Genomic data are well correlated between studies; however, the measured drug response data are highly discordant. Although the source of inconsistencies remains uncertain, it has potential implications for using...

  12. Strategic Management of Large Projects

    Institute of Scientific and Technical Information of China (English)

    WangYingluo; LiuYi; LiYuan

    2004-01-01

    The strategic management of large projects is both theoretically and practically important. Some scholars have advanced flexible strategy theory in China. The difference of strategic flexibility and flexible strategy is pointed out. The supporting system and characteristics of flexible strategy are analyzed. The changes of flexible strategy and integration of strategic management are discussed.

  13. Mass spectrometry of large molecules

    International Nuclear Information System (INIS)

    Facchetti, S.

    1985-01-01

    The lectures in this volume were given at a course on mass spectrometry of large molecules, organized within the framework of the Training and Education programme of the Joint Research Centre of the European Communities. Although first presented in 1983, most of the lectures have since been updated by their authors. (orig.)

  14. Large for Gestational Age (LGA)

    Science.gov (United States)

    ... mother Other risk factors for having large-for-gestational-age newborns include Maternal obesity Having had previous LGA babies Genetic abnormalities or syndromes (for example, Beckwith-Wiedemann syndrome or Sotos syndrome) Excessive weight gain during pregnancy (the fetus gets more calories as ...

  15. Large-scale pool fires

    Directory of Open Access Journals (Sweden)

    Steinhaus Thomas

    2007-01-01

    Full Text Available A review of research into the burning behavior of large pool fires and fuel spill fires is presented. The features which distinguish such fires from smaller pool fires are mainly associated with the fire dynamics at low source Froude numbers and the radiative interaction with the fire source. In hydrocarbon fires, higher soot levels at increased diameters result in radiation blockage effects around the perimeter of large fire plumes; this yields lower emissive powers and a drastic reduction in the radiative loss fraction; whilst there are simplifying factors with these phenomena, arising from the fact that soot yield can saturate, there are other complications deriving from the intermittency of the behavior, with luminous regions of efficient combustion appearing randomly in the outer surface of the fire according the turbulent fluctuations in the fire plume. Knowledge of the fluid flow instabilities, which lead to the formation of large eddies, is also key to understanding the behavior of large-scale fires. Here modeling tools can be effectively exploited in order to investigate the fluid flow phenomena, including RANS- and LES-based computational fluid dynamics codes. The latter are well-suited to representation of the turbulent motions, but a number of challenges remain with their practical application. Massively-parallel computational resources are likely to be necessary in order to be able to adequately address the complex coupled phenomena to the level of detail that is necessary.

  16. Active Learning in Large Classes

    DEFF Research Database (Denmark)

    Gørtz, Inge Li

    2011-01-01

    teaching large classes (more than 50 students), and describe how we successfully have in a second semester course in the Bachelor of Engineering (BEng) and Bachelor of Science Engineering (BSc Eng) program at the Technical University of Denmark (DTU). Approximately 200 students is attending...

  17. Adding large EM stack support

    KAUST Repository

    Holst, Glendon

    2016-12-01

    Serial section electron microscopy (SSEM) image stacks generated using high throughput microscopy techniques are an integral tool for investigating brain connectivity and cell morphology. FIB or 3View scanning electron microscopes easily generate gigabytes of data. In order to produce analyzable 3D dataset from the imaged volumes, efficient and reliable image segmentation is crucial. Classical manual approaches to segmentation are time consuming and labour intensive. Semiautomatic seeded watershed segmentation algorithms, such as those implemented by ilastik image processing software, are a very powerful alternative, substantially speeding up segmentation times. We have used ilastik effectively for small EM stacks – on a laptop, no less; however, ilastik was unable to carve the large EM stacks we needed to segment because its memory requirements grew too large – even for the biggest workstations we had available. For this reason, we refactored the carving module of ilastik to scale it up to large EM stacks on large workstations, and tested its efficiency. We modified the carving module, building on existing blockwise processing functionality to process data in manageable chunks that can fit within RAM (main memory). We review this refactoring work, highlighting the software architecture, design choices, modifications, and issues encountered.

  18. Protection of large capacitor banks

    International Nuclear Information System (INIS)

    Sprott, J.C.; Lovell, T.W.

    1982-06-01

    Large capacitor banks, as used in many pulsed plasma experiments, are subject to catastrophic failure in the event of a short in the output or in an individual capacitor. Methods are described for protecting such banks to minimize the damage and down-time caused by such a failure

  19. CERN's Large Hadron Collider project

    Science.gov (United States)

    Fearnley, Tom A.

    1997-03-01

    The paper gives a brief overview of CERN's Large Hadron Collider (LHC) project. After an outline of the physics motivation, we describe the LHC machine, interaction rates, experimental challenges, and some important physics channels to be studied. Finally we discuss the four experiments planned at the LHC: ATLAS, CMS, ALICE and LHC-B.

  20. CERN's Large Hadron Collider project

    International Nuclear Information System (INIS)

    Fearnley, Tom A.

    1997-01-01

    The paper gives a brief overview of CERN's Large Hadron Collider (LHC) project. After an outline of the physics motivation, we describe the LHC machine, interaction rates, experimental challenges, and some important physics channels to be studied. Finally we discuss the four experiments planned at the LHC: ATLAS, CMS, ALICE and LHC-B

  1. Large area CMOS image sensors

    International Nuclear Information System (INIS)

    Turchetta, R; Guerrini, N; Sedgwick, I

    2011-01-01

    CMOS image sensors, also known as CMOS Active Pixel Sensors (APS) or Monolithic Active Pixel Sensors (MAPS), are today the dominant imaging devices. They are omnipresent in our daily life, as image sensors in cellular phones, web cams, digital cameras, ... In these applications, the pixels can be very small, in the micron range, and the sensors themselves tend to be limited in size. However, many scientific applications, like particle or X-ray detection, require large format, often with large pixels, as well as other specific performance, like low noise, radiation hardness or very fast readout. The sensors are also required to be sensitive to a broad spectrum of radiation: photons from the silicon cut-off in the IR down to UV and X- and gamma-rays through the visible spectrum as well as charged particles. This requirement calls for modifications to the substrate to be introduced to provide optimized sensitivity. This paper will review existing CMOS image sensors, whose size can be as large as a single CMOS wafer, and analyse the technical requirements and specific challenges of large format CMOS image sensors.

  2. The large hadron collider project

    International Nuclear Information System (INIS)

    Maiani, L.

    1999-01-01

    Knowledge of the fundamental constituents of matter has greatly advanced, over the last decades. The standard theory of fundamental interactions presents us with a theoretically sound picture, which describes with great accuracy known physical phenomena on most diverse energy and distance scales. These range from 10 -16 cm, inside the nucleons, up to large-scale astrophysical bodies, including the early Universe at some nanosecond after the Big-Bang and temperatures of the order of 10 2 GeV. The picture is not yet completed, however, as we lack the observation of the Higgs boson, predicted in the 100-500 GeV range - a particle associated with the generation of particle masses and with the quantum fluctuations in the primordial Universe. In addition, the standard theory is expected to undergo a change of regime in the 10 3 GeV region, with the appearance of new families of particles, most likely associated with the onset of a new symmetry (supersymmetry). In 1994, the CERN Council approved the construction of the large hadron collider (LHC), a proton-proton collider of a new design to be installed in the existing LEP tunnel, with an energy of 7 TeV per beam and extremely large luminosity, of ∝10 34 cm -2 s -1 . Construction was started in 1996, with the additional support of the US, Japan, Russia, Canada and other European countries, making the LHC a really global project, the first one in particle physics. After a short review of the physics scenario, I report on the present status of the LHC construction. Special attention is given to technological problems such as the realization of the super-conducting dipoles, following an extensive R and D program with European industries. The construction of the large LHC detectors has required a vast R and D program by a large international community, to overcome the problems posed by the complexity of the collisions and by the large luminosity of the machine. (orig.)

  3. Degassing a large LHe cryopump

    International Nuclear Information System (INIS)

    Denhoy, B.S.; Batzer, T.H.; Call, W.R.

    1977-01-01

    A method has been developed and successfully tested to degas a large LHe cryopump. Use of this method inhibits the normally excessive pressure rise during the degassing cycle when the degassing rate exceeds the external pumping capabilities of the system. A small appendage pump, installed close to the main cryopump, absorbs all the gas, as it is desorbed from the main cryopump, with no rise in the system pressure. The appendage pump can then be isolated from the main vacuum system and degassed at high pressure. We pumped 15 to 20 x 10 3 Torr . 1 of H 2 on a 1.25 m 2 panel. During the degassing cycle the system pressure never rose above 1 x 10 -4 Torr. In large vacuum systems for future fusion machines that contain cryopump panels as well as cryogenic magnets, this method is a unique and very useful tool. It will allow the degassing of cryopumps without affecting the temperature equilibrium of cryogenic magnets

  4. Large-capacity current leads

    International Nuclear Information System (INIS)

    Ballarino, A.

    2008-01-01

    Feeding superconducting magnets with reliable low-loss devices is a key issue for any cryo-electrical system. Conventional or HTS current leads can be used, and cooling methods, materials, and geometries can be chosen to optimize the thermo-electrical performance of the system. The LHC magnets are powered via more than 3000 current leads transporting altogether about 3 MA of current. With thousands of leads, the LHC lead project represents today the largest project of its kind ever undertaken. Following a review of the LHC lead project, an overview of the choices that can be made for the optimization of large capacity current leads is presented. Examples are given of other leads for large scale magnet systems for which the use of HTS is being envisaged

  5. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Wiseman, G.W.

    1980-06-01

    The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

  6. Parametric instabilities in large plasmas

    International Nuclear Information System (INIS)

    Brambilla, Marco; Liberman, Bernardo.

    1979-01-01

    Parametric decay processes in large plasmas are considered as the linear stage of a three wave interaction (pump, sideband and beat wave) in which the amplitude of the externally excited pump is sufficiently large to neglect pump depletion to first order, yet sufficiently small to allow a linearized treatment of the pump propagation to zeroth order. The coupling coefficients are then obtained from an iterative solution of Vlasov equation, and a compact expression is derived, in which the multiple series over Bessel functions is explicitly summed. Even in the limit of a very long wavelength pump, the dispersion relation obtained in this way does not coincide with the one obtained using the well-known ''dipole'' approximation, unless both the sideband and beat wave are resonant modes of the plasma. An analysis of the origin of this discrepancy allows us to conclude that ''quasimodes'' (evanescent waves driven absolutely unstable by the pump) are more correctly described by the iterative approach

  7. Plasma diagnostics on large tokamaks

    International Nuclear Information System (INIS)

    Orlinskij, D.V.; Magyar, G.

    1988-01-01

    The main tasks of the large tokamaks which are under construction (T-15 and Tore Supra) and of those which have already been built (TFTR, JET, JT-60 and DIII-D) together with their design features which are relevant to plasma diagnostics are briefly discussed. The structural features and principal characteristics of the diagnostic systems being developed or already being used on these devices are also examined. The different diagnostic methods are described according to the physical quantities to be measured: electric and magnetic diagnostics, measurements of electron density, electron temperature, the ion components of the plasma, radiation loss measurements, spectroscopy of impurities, edge diagnostics and study of plasma stability. The main parameters of the various diagnostic systems used on the six large tokamaks are summarized in tables. (author). 351 refs, 44 figs, 22 tabs

  8. Foam rheology at large deformation

    Science.gov (United States)

    Géminard, J.-C.; Pastenes, J. C.; Melo, F.

    2018-04-01

    Large deformations are prone to cause irreversible changes in materials structure, generally leading to either material hardening or softening. Aqueous foam is a metastable disordered structure of densely packed gas bubbles. We report on the mechanical response of a foam layer subjected to quasistatic periodic shear at large amplitude. We observe that, upon increasing shear, the shear stress follows a universal curve that is nearly exponential and tends to an asymptotic stress value interpreted as the critical yield stress at which the foam structure is completely remodeled. Relevant trends of the foam mechanical response to cycling are mathematically reproduced through a simple law accounting for the amount of plastic deformation upon increasing stress. This view provides a natural interpretation to stress hardening in foams, demonstrating that plastic effects are present in this material even for minute deformation.

  9. Physics with large extra dimensions

    CERN Document Server

    Antoniadis, Ignatios

    2004-01-01

    The recent understanding of string theory opens the possibility that the string scale can be as low as a few TeV. The apparent weakness of gravitational interactions can then be accounted by the existence of large internal dimensions, in the submillimeter region. Furthermore, our world must be confined to live on a brane transverse to these large dimensions, with which it interacts only gravitationally. In my lecture, I describe briefly this scenario which gives a new theoretical framework for solving the gauge hierarchy problem and the unification of all interactions. I also discuss its main properties and implications for observations at both future particle colliders, and in non-accelerator gravity experiments. Such effects are for instance the production of Kaluza-Klein resonances, graviton emission in the bulk of extra dimensions, and a radical change of gravitational forces in the submillimeter range.

  10. Chunking of Large Multidimensional Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rotem, Doron; Otoo, Ekow J.; Seshadri, Sridhar

    2007-02-28

    Data intensive scientific computations as well on-lineanalytical processing applications as are done on very large datasetsthat are modeled as k-dimensional arrays. The storage organization ofsuch arrays on disks is done by partitioning the large global array intofixed size hyper-rectangular sub-arrays called chunks or tiles that formthe units of data transfer between disk and memory. Typical queriesinvolve the retrieval of sub-arrays in a manner that accesses all chunksthat overlap the query results. An important metric of the storageefficiency is the expected number of chunks retrieved over all suchqueries. The question that immediately arises is "what shapes of arraychunks give the minimum expected number of chunks over a query workload?"In this paper we develop two probabilistic mathematical models of theproblem and provide exact solutions using steepest descent and geometricprogramming methods. Experimental results, using synthetic workloads onreal life data sets, show that our chunking is much more efficient thanthe existing approximate solutions.

  11. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    These antimicrobial peptides are implicated in the resistance of epithelial surfaces to microbial colonisation and have been shown to be upregulated...be equivalent to standard autograft repair in rodent models. Outcomes have now been validated in a large animal (swine) model with 5 cm ulnar nerve...Goals of the Project Task 1– Determine mechanical properties, seal strength and resistance to biodegradation of candidate photochemical nerve wrap

  12. Community Detection for Large Graphs

    KAUST Repository

    Peng, Chengbin

    2014-05-04

    Many real world networks have inherent community structures, including social networks, transportation networks, biological networks, etc. For large scale networks with millions or billions of nodes in real-world applications, accelerating current community detection algorithms is in demand, and we present two approaches to tackle this issue -A K-core based framework that can accelerate existing community detection algorithms significantly; -A parallel inference algorithm via stochastic block models that can distribute the workload.

  13. Large floating structures technological advances

    CERN Document Server

    Wang, BT

    2015-01-01

    This book surveys key projects that have seen the construction of large floating structures or have attained detailed conceptual designs. This compilation of key floating structures in a single volume captures the innovative features that mark the technological advances made in this field of engineering, and will provide a useful reference for ideas, analysis, design, and construction of these unique and emerging urban projects to offshore and marine engineers, urban planners, architects and students.

  14. Visualising large hierarchies with Flextree

    Science.gov (United States)

    Song, Hongzhi; Curran, Edwin P.; Sterritt, Roy

    2003-05-01

    One of the main tasks in Information Visualisation research is creating visual tools to facilitate human understanding of large and complex information spaces. Hierarchies, being a good mechanism in organising such information, are ubiquitous. Although much research effort has been spent on finding useful representations for hierarchies, visualising large hierarchies is still a difficult topic. One of the difficulties is how to show both tructure and node content information in one view. Another is how to achieve multiple foci in a focus+context visualisation. This paper describes a novel hierarchy visualisation technique called FlexTree to address these problems. It contains some important features that have not been exploited so far. In this visualisation, a profile or contour unique to the hierarchy being visualised can be gained in a histogram-like layout. A normalised view of a common attribute of all nodes can be acquired, and selection of this attribute is controllable by the user. Multiple foci are consistently accessible within a global context through interaction. Furthermore it can handle a large hierarchy that contains several thousand nodes in a PC environment. In addition results from an informal evaluation are also presented.

  15. The large sample size fallacy.

    Science.gov (United States)

    Lantz, Björn

    2013-06-01

    Significance in the statistical sense has little to do with significance in the common practical sense. Statistical significance is a necessary but not a sufficient condition for practical significance. Hence, results that are extremely statistically significant may be highly nonsignificant in practice. The degree of practical significance is generally determined by the size of the observed effect, not the p-value. The results of studies based on large samples are often characterized by extreme statistical significance despite small or even trivial effect sizes. Interpreting such results as significant in practice without further analysis is referred to as the large sample size fallacy in this article. The aim of this article is to explore the relevance of the large sample size fallacy in contemporary nursing research. Relatively few nursing articles display explicit measures of observed effect sizes or include a qualitative discussion of observed effect sizes. Statistical significance is often treated as an end in itself. Effect sizes should generally be calculated and presented along with p-values for statistically significant results, and observed effect sizes should be discussed qualitatively through direct and explicit comparisons with the effects in related literature. © 2012 Nordic College of Caring Science.

  16. Large nuclear steam turbine plants

    International Nuclear Information System (INIS)

    Urushidani, Haruo; Moriya, Shin-ichi; Tsuji, Kunio; Fujita, Isao; Ebata, Sakae; Nagai, Yoji.

    1986-01-01

    The technical development of the large capacity steam turbines for ABWR plants was partially completed, and that in progress is expected to be completed soon. In this report, the outline of those new technologies is described. As the technologies for increasing the capacity and heightening the efficiency, 52 in long blades and moisture separating heaters are explained. Besides, in the large bore butterfly valves developed for making the layout compact, the effect of thermal efficiency rise due to the reduction of pressure loss can be expected. As the new technology on the system side, the simplification of the turbine system and the effect of heightening the thermal efficiency by high pressure and low pressure drain pumping-up method based on the recent improvement of feed water quality are discussed. As for nuclear steam turbines, the actual records of performance of 1100 MW class, the largest output at present, have been obtained, and as a next large capacity machine, the development of a steam turbine of 1300 MWe class for an ABWR plant is in progress. It can be expected that by the introduction of those new technologies, the plants having high economical efficiency are realized. (Kako, I.)

  17. Perturbation theory in large order

    International Nuclear Information System (INIS)

    Bender, C.M.

    1978-01-01

    For many quantum mechanical models, the behavior of perturbation theory in large order is strikingly simple. For example, in the quantum anharmonic oscillator, which is defined by -y'' + (x 2 /4 + ex 4 /4 - E) y = 0, y ( +- infinity) = 0, the perturbation coefficients, A/sub n/, in the expansion for the ground-state energy, E(ground state) approx. EPSILON/sub n = 0//sup infinity/ A/sub n/epsilon/sup n/, simplify dramatically as n → infinity: A/sub n/ approx. (6/π 3 )/sup 1/2/(-3)/sup n/GAMMA(n + 1/2). Methods of applied mathematics are used to investigate the nature of perturbation theory in quantum mechanics and show that its large-order behavior is determined by the semiclassical content of the theory. In quantum field theory the perturbation coefficients are computed by summing Feynman graphs. A statistical procedure in a simple lambda phi 4 model for summing the set of all graphs as the number of vertices → infinity is presented. Finally, the connection between the large-order behavior of perturbation theory in quantum electrodynamics and the value of α, the charge on the electron, is discussed. 7 figures

  18. Foreshock occurrence before large earthquakes

    Science.gov (United States)

    Reasenberg, P.A.

    1999-01-01

    Rates of foreshock occurrence involving shallow M ??? 6 and M ??? 7 mainshocks and M ??? 5 foreshocks were measured in two worldwide catalogs over ???20-year intervals. The overall rates observed are similar to ones measured in previous worldwide and regional studies when they are normalized for the ranges of magnitude difference they each span. The observed worldwide rates were compared to a generic model of earthquake clustering based on patterns of small and moderate aftershocks in California. The aftershock model was extended to the case of moderate foreshocks preceding large mainshocks. Overall, the observed worldwide foreshock rates exceed the extended California generic model by a factor of ???2. Significant differences in foreshock rate were found among subsets of earthquakes defined by their focal mechanism and tectonic region, with the rate before thrust events higher and the rate before strike-slip events lower than the worldwide average. Among the thrust events, a large majority, composed of events located in shallow subduction zones, had a high foreshock rate, while a minority, located in continental thrust belts, had a low rate. These differences may explain why previous surveys have found low foreshock rates among thrust events in California (especially southern California), while the worldwide observations suggests the opposite: California, lacking an active subduction zone in most of its territory, and including a region of mountain-building thrusts in the south, reflects the low rate apparently typical for continental thrusts, while the worldwide observations, dominated by shallow subduction zone events, are foreshock-rich. If this is so, then the California generic model may significantly underestimate the conditional probability for a very large (M ??? 8) earthquake following a potential (M ??? 7) foreshock in Cascadia. The magnitude differences among the identified foreshock-mainshock pairs in the Harvard catalog are consistent with a uniform

  19. Large number discrimination by mosquitofish.

    Directory of Open Access Journals (Sweden)

    Christian Agrillo

    Full Text Available BACKGROUND: Recent studies have demonstrated that fish display rudimentary numerical abilities similar to those observed in mammals and birds. The mechanisms underlying the discrimination of small quantities (<4 were recently investigated while, to date, no study has examined the discrimination of large numerosities in fish. METHODOLOGY/PRINCIPAL FINDINGS: Subjects were trained to discriminate between two sets of small geometric figures using social reinforcement. In the first experiment mosquitofish were required to discriminate 4 from 8 objects with or without experimental control of the continuous variables that co-vary with number (area, space, density, total luminance. Results showed that fish can use the sole numerical information to compare quantities but that they preferentially use cumulative surface area as a proxy of the number when this information is available. A second experiment investigated the influence of the total number of elements to discriminate large quantities. Fish proved to be able to discriminate up to 100 vs. 200 objects, without showing any significant decrease in accuracy compared with the 4 vs. 8 discrimination. The third experiment investigated the influence of the ratio between the numerosities. Performance was found to decrease when decreasing the numerical distance. Fish were able to discriminate numbers when ratios were 1:2 or 2:3 but not when the ratio was 3:4. The performance of a sample of undergraduate students, tested non-verbally using the same sets of stimuli, largely overlapped that of fish. CONCLUSIONS/SIGNIFICANCE: Fish are able to use pure numerical information when discriminating between quantities larger than 4 units. As observed in human and non-human primates, the numerical system of fish appears to have virtually no upper limit while the numerical ratio has a clear effect on performance. These similarities further reinforce the view of a common origin of non-verbal numerical systems in all

  20. Radiosurgery for Large Brain Metastases

    International Nuclear Information System (INIS)

    Han, Jung Ho; Kim, Dong Gyu; Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee; Jung, Hee-Won

    2012-01-01

    Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery. Patients and Methods: Eighty patients with large brain metastases (>14 cm 3 ) were treated with radiosurgery between 1998 and 2009. The mean age was 59 ± 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 ± 8.8 cm 3 , and the mean marginal dose prescribed was 13.8 ± 2.2 Gy. Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343–10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1–4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of ≥11 Gy, and a tumor volume ≥26 cm 3 were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261–0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171–0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274–4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%). Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

  1. Large-bore pipe decontamination

    International Nuclear Information System (INIS)

    Ebadian, M.A.

    1998-01-01

    The decontamination and decommissioning (D and D) of 1200 buildings within the US Department of Energy-Office of Environmental Management (DOE-EM) Complex will require the disposition of miles of pipe. The disposition of large-bore pipe, in particular, presents difficulties in the area of decontamination and characterization. The pipe is potentially contaminated internally as well as externally. This situation requires a system capable of decontaminating and characterizing both the inside and outside of the pipe. Current decontamination and characterization systems are not designed for application to this geometry, making the direct disposal of piping systems necessary in many cases. The pipe often creates voids in the disposal cell, which requires the pipe to be cut in half or filled with a grout material. These methods are labor intensive and costly to perform on large volumes of pipe. Direct disposal does not take advantage of recycling, which could provide monetary dividends. To facilitate the decontamination and characterization of large-bore piping and thereby reduce the volume of piping required for disposal, a detailed analysis will be conducted to document the pipe remediation problem set; determine potential technologies to solve this remediation problem set; design and laboratory test potential decontamination and characterization technologies; fabricate a prototype system; provide a cost-benefit analysis of the proposed system; and transfer the technology to industry. This report summarizes the activities performed during fiscal year 1997 and describes the planned activities for fiscal year 1998. Accomplishments for FY97 include the development of the applicable and relevant and appropriate regulations, the screening of decontamination and characterization technologies, and the selection and initial design of the decontamination system

  2. The IEA Large Coil Task

    International Nuclear Information System (INIS)

    Beard, D.S.; Klose, W.; Shimamoto, S.; Vecsey, G.

    1988-01-01

    A multinational program of cooperative research, development, demonstrations, and exchanges of information on superconducting magnets for fusion was initiated in 1977 under an IEA agreement. The first major step in the development of TF magnets was called the Large Coil Task. Participants in LCT were the U.S. DOE, EURATOM, JAERI, and the Departement Federal de l'Interieur of Switzerland. The goals of LCT were to obtain experimental data, to demonstrate reliable operation of large superconducting coils, and to prove design principles and fabrication techniques being considered for the toroidal magnets of thermonuclear reactors. These goals were to be accomplished through coordinated but largely independent design, development, and construction of six test coils, followed by collaborative testing in a compact toroidal test array at fields of 8 T and higher. Under the terms of the IEA Agreement, the United States built and operated the test facility at Oak Ridge and provided three test coils. The other participants provided one coil each. Information on design and manufacturing and all test data were shared by all. The LCT team of each participant included a government laboratory and industrial partners or contractors. The last coil was completed in 1985, and the test assembly was completed in October of that year. Over the next 23 months, the six-coil array was cooled down and extensive testing was performed. Results were gratifying, as tests achieved design-point performance and well beyond. (Each coil reached a peak field of 9 T.) Experiments elucidated coil behavior, delineated limits of operability, and demonstrated coil safety. (orig./KP)

  3. Large block test status report

    International Nuclear Information System (INIS)

    Wilder, D.G.; Lin, W.; Blair, S.C.

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved

  4. Large volume cryogenic silicon detectors

    International Nuclear Information System (INIS)

    Braggio, C.; Boscardin, M.; Bressi, G.; Carugno, G.; Corti, D.; Galeazzi, G.; Zorzi, N.

    2009-01-01

    We present preliminary measurements for the development of a large volume silicon detector to detect low energy and low rate energy depositions. The tested detector is a one cm-thick silicon PIN diode with an active volume of 31 cm 3 , cooled to the liquid helium temperature to obtain depletion from thermally-generated free carriers. A thorough study has been done to show that effects of charge trapping during drift disappears at a bias field value of the order of 100V/cm.

  5. Large volume cryogenic silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Braggio, C. [Dipartimento di Fisica, Universita di Padova, via Marzolo 8, 35131 Padova (Italy); Boscardin, M. [Fondazione Bruno Kessler (FBK), via Sommarive 18, I-38100 Povo (Italy); Bressi, G. [INFN sez. di Pavia, via Bassi 6, 27100 Pavia (Italy); Carugno, G.; Corti, D. [INFN sez. di Padova, via Marzolo 8, 35131 Padova (Italy); Galeazzi, G. [INFN lab. naz. Legnaro, viale dell' Universita 2, 35020 Legnaro (Italy); Zorzi, N. [Fondazione Bruno Kessler (FBK), via Sommarive 18, I-38100 Povo (Italy)

    2009-12-15

    We present preliminary measurements for the development of a large volume silicon detector to detect low energy and low rate energy depositions. The tested detector is a one cm-thick silicon PIN diode with an active volume of 31 cm{sup 3}, cooled to the liquid helium temperature to obtain depletion from thermally-generated free carriers. A thorough study has been done to show that effects of charge trapping during drift disappears at a bias field value of the order of 100V/cm.

  6. Large area and flexible electronics

    CERN Document Server

    Caironi, Mario

    2015-01-01

    From materials to applications, this ready reference covers the entire value chain from fundamentals via processing right up to devices, presenting different approaches to large-area electronics, thus enabling readers to compare materials, properties and performance.Divided into two parts, the first focuses on the materials used for the electronic functionality, covering organic and inorganic semiconductors, including vacuum and solution-processed metal-oxide semiconductors, nanomembranes and nanocrystals, as well as conductors and insulators. The second part reviews the devices and applicatio

  7. Japanese large-scale interferometers

    CERN Document Server

    Kuroda, K; Miyoki, S; Ishizuka, H; Taylor, C T; Yamamoto, K; Miyakawa, O; Fujimoto, M K; Kawamura, S; Takahashi, R; Yamazaki, T; Arai, K; Tatsumi, D; Ueda, A; Fukushima, M; Sato, S; Shintomi, T; Yamamoto, A; Suzuki, T; Saitô, Y; Haruyama, T; Sato, N; Higashi, Y; Uchiyama, T; Tomaru, T; Tsubono, K; Ando, M; Takamori, A; Numata, K; Ueda, K I; Yoneda, H; Nakagawa, K; Musha, M; Mio, N; Moriwaki, S; Somiya, K; Araya, A; Kanda, N; Telada, S; Sasaki, M; Tagoshi, H; Nakamura, T; Tanaka, T; Ohara, K

    2002-01-01

    The objective of the TAMA 300 interferometer was to develop advanced technologies for kilometre scale interferometers and to observe gravitational wave events in nearby galaxies. It was designed as a power-recycled Fabry-Perot-Michelson interferometer and was intended as a step towards a final interferometer in Japan. The present successful status of TAMA is presented. TAMA forms a basis for LCGT (large-scale cryogenic gravitational wave telescope), a 3 km scale cryogenic interferometer to be built in the Kamioka mine in Japan, implementing cryogenic mirror techniques. The plan of LCGT is schematically described along with its associated R and D.

  8. Large spin systematics in CFT

    Energy Technology Data Exchange (ETDEWEB)

    Alday, Luis F.; Bissi, Agnese; Łukowski, Tomasz [Mathematical Institute, University of Oxford,Andrew Wiles Building, Radcliffe Observatory Quarter,Woodstock Road, Oxford, OX2 6GG (United Kingdom)

    2015-11-16

    Using conformal field theory (CFT) arguments we derive an infinite number of constraints on the large spin expansion of the anomalous dimensions and structure constants of higher spin operators. These arguments rely only on analyticity, unitarity, crossing-symmetry and the structure of the conformal partial wave expansion. We obtain results for both, perturbative CFT to all order in the perturbation parameter, as well as non-perturbatively. For the case of conformal gauge theories this provides a proof of the reciprocity principle to all orders in perturbation theory and provides a new “reciprocity' principle for structure constants. We argue that these results extend also to non-conformal theories.

  9. Large spin systematics in CFT

    International Nuclear Information System (INIS)

    Alday, Luis F.; Bissi, Agnese; Łukowski, Tomasz

    2015-01-01

    Using conformal field theory (CFT) arguments we derive an infinite number of constraints on the large spin expansion of the anomalous dimensions and structure constants of higher spin operators. These arguments rely only on analyticity, unitarity, crossing-symmetry and the structure of the conformal partial wave expansion. We obtain results for both, perturbative CFT to all order in the perturbation parameter, as well as non-perturbatively. For the case of conformal gauge theories this provides a proof of the reciprocity principle to all orders in perturbation theory and provides a new “reciprocity' principle for structure constants. We argue that these results extend also to non-conformal theories.

  10. Quick Mining of Isomorphic Exact Large Patterns from Large Graphs

    KAUST Repository

    Almasri, Islam

    2014-12-01

    The applications of the sub graph isomorphism search are growing with the growing number of areas that model their systems using graphs or networks. Specifically, many biological systems, such as protein interaction networks, molecular structures and protein contact maps, are modeled as graphs. The sub graph isomorphism search is concerned with finding all sub graphs that are isomorphic to a relevant query graph, the existence of such sub graphs can reflect on the characteristics of the modeled system. The most computationally expensive step in the search for isomorphic sub graphs is the backtracking algorithm that traverses the nodes of the target graph. In this paper, we propose a pruning approach that is inspired by the minimum remaining value heuristic that achieves greater scalability over large query and target graphs. Our testing on various biological networks shows that performance enhancement of our approach over existing state-of-the-art approaches varies between 6x and 53x. © 2014 IEEE.

  11. Quick Mining of Isomorphic Exact Large Patterns from Large Graphs

    KAUST Repository

    Almasri, Islam; Gao, Xin; Fedoroff, Nina V.

    2014-01-01

    The applications of the sub graph isomorphism search are growing with the growing number of areas that model their systems using graphs or networks. Specifically, many biological systems, such as protein interaction networks, molecular structures and protein contact maps, are modeled as graphs. The sub graph isomorphism search is concerned with finding all sub graphs that are isomorphic to a relevant query graph, the existence of such sub graphs can reflect on the characteristics of the modeled system. The most computationally expensive step in the search for isomorphic sub graphs is the backtracking algorithm that traverses the nodes of the target graph. In this paper, we propose a pruning approach that is inspired by the minimum remaining value heuristic that achieves greater scalability over large query and target graphs. Our testing on various biological networks shows that performance enhancement of our approach over existing state-of-the-art approaches varies between 6x and 53x. © 2014 IEEE.

  12. Quantum chromodynamics at large distances

    International Nuclear Information System (INIS)

    Arbuzov, B.A.

    1987-01-01

    Properties of QCD at large distances are considered in the framework of traditional quantum field theory. An investigation of asymptotic behaviour of lower Green functions in QCD is the starting point of the approach. The recent works are reviewed which confirm the singular infrared behaviour of gluon propagator M 2 /(k 2 ) 2 at least under some gauge conditions. A special covariant gauge comes out to be the most suitable for description of infrared region due to absence of ghost contributions to infrared asymptotics of Green functions. Solutions of Schwinger-Dyson equation for quark propagator are obtained in this special gauge and are shown to possess desirable properties: spontaneous breaking of chiral invariance and nonperturbative character. The infrared asymptotics of lower Green functions are used for calculation of vacuum expectation values of gluon and quark fields. These vacuum expectation values are obtained in a good agreement with the corresponding phenomenological values which are needed in the method of sum rules in QCD, that confirms adequacy of the infrared region description. The consideration of a behaviour of QCD at large distances leads to the conclusion that at contemporary stage of theory development one may consider two possibilities. The first one is the well-known confinement hypothesis and the second one is called incomplete confinement and stipulates for open color to be observable. Possible manifestations of incomplete confinement are discussed

  13. Large scale cluster computing workshop

    International Nuclear Information System (INIS)

    Dane Skow; Alan Silverman

    2002-01-01

    Recent revolutions in computer hardware and software technologies have paved the way for the large-scale deployment of clusters of commodity computers to address problems heretofore the domain of tightly coupled SMP processors. Near term projects within High Energy Physics and other computing communities will deploy clusters of scale 1000s of processors and be used by 100s to 1000s of independent users. This will expand the reach in both dimensions by an order of magnitude from the current successful production facilities. The goals of this workshop were: (1) to determine what tools exist which can scale up to the cluster sizes foreseen for the next generation of HENP experiments (several thousand nodes) and by implication to identify areas where some investment of money or effort is likely to be needed. (2) To compare and record experimences gained with such tools. (3) To produce a practical guide to all stages of planning, installing, building and operating a large computing cluster in HENP. (4) To identify and connect groups with similar interest within HENP and the larger clustering community

  14. Nonlinear electrokinetics at large voltages

    Energy Technology Data Exchange (ETDEWEB)

    Bazant, Martin Z [Department of Chemical Engineering and Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Sabri Kilic, Mustafa; Ajdari, Armand [Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Storey, Brian D [Franklin W Olin College of Engineering, Needham, MA 02492 (United States)], E-mail: bazant@mit.edu

    2009-07-15

    The classical theory of electrokinetic phenomena assumes a dilute solution of point-like ions in chemical equilibrium with a surface whose double-layer voltage is of order the thermal voltage, k{sub B}T/e=25 mV. In nonlinear 'induced-charge' electrokinetic phenomena, such as ac electro-osmosis, several volts {approx}100k{sub B}T/e are applied to the double layer, and the theory breaks down and cannot explain many observed features. We argue that, under such a large voltage, counterions 'condense' near the surface, even for dilute bulk solutions. Based on simple models, we predict that the double-layer capacitance decreases and the electro-osmotic mobility saturates at large voltages, due to steric repulsion and increased viscosity of the condensed layer, respectively. The former suffices to explain observed high-frequency flow reversal in ac electro-osmosis; the latter leads to a salt concentration dependence of induced-charge flows comparable to experiments, although a complete theory is still lacking.

  15. Large shaft development test plan

    International Nuclear Information System (INIS)

    Krug, A.D.

    1984-03-01

    This test plan proposes the conduct of a large shaft development test at the Hanford site in support of the repository development program. The purpose and objective of the test plan is to obtain the information necessary to establish feasibility and to predict the performance of the drilling system used to drill large diameter shafts. The test plan is based upon drilling a 20 ft diameter shaft to a depth of 1,000 feet. The test plan specifies series of tests to evaluate the performance of the downhole assembly, the performance of the rig, and the ability of the system to cope with geologic hazards. The quality of the hole produced will also be determined. This test plan is considered to be preliminary in that it was prepared as input for the decision to determine if development testing is required in this area. Should the decision be made to proceed with development testing, this test plan shall be updated and revised. 6 refs., 2 figs., 3 tabs

  16. How Large Asexual Populations Adapt

    Science.gov (United States)

    Desai, Michael

    2007-03-01

    We often think of beneficial mutations as being rare, and of adaptation as a sequence of selected substitutions: a beneficial mutation occurs, spreads through a population in a selective sweep, then later another beneficial mutation occurs, and so on. This simple picture is the basis for much of our intuition about adaptive evolution, and underlies a number of practical techniques for analyzing sequence data. Yet many large and mostly asexual populations -- including a wide variety of unicellular organisms and viruses -- live in a very different world. In these populations, beneficial mutations are common, and frequently interfere or cooperate with one another as they all attempt to sweep simultaneously. This radically changes the way these populations adapt: rather than an orderly sequence of selective sweeps, evolution is a constant swarm of competing and interfering mutations. I will describe some aspects of these dynamics, including why large asexual populations cannot evolve very quickly and the character of the diversity they maintain. I will explain how this changes our expectations of sequence data, how sex can help a population adapt, and the potential role of ``mutator'' phenotypes with abnormally high mutation rates. Finally, I will discuss comparisons of these predictions with evolution experiments in laboratory yeast populations.

  17. Creating Large Scale Database Servers

    International Nuclear Information System (INIS)

    Becla, Jacek

    2001-01-01

    The BaBar experiment at the Stanford Linear Accelerator Center (SLAC) is designed to perform a high precision investigation of the decays of the B-meson produced from electron-positron interactions. The experiment, started in May 1999, will generate approximately 300TB/year of data for 10 years. All of the data will reside in Objectivity databases accessible via the Advanced Multi-threaded Server (AMS). To date, over 70TB of data have been placed in Objectivity/DB, making it one of the largest databases in the world. Providing access to such a large quantity of data through a database server is a daunting task. A full-scale testbed environment had to be developed to tune various software parameters and a fundamental change had to occur in the AMS architecture to allow it to scale past several hundred terabytes of data. Additionally, several protocol extensions had to be implemented to provide practical access to large quantities of data. This paper will describe the design of the database and the changes that we needed to make in the AMS for scalability reasons and how the lessons we learned would be applicable to virtually any kind of database server seeking to operate in the Petabyte region

  18. Creating Large Scale Database Servers

    Energy Technology Data Exchange (ETDEWEB)

    Becla, Jacek

    2001-12-14

    The BaBar experiment at the Stanford Linear Accelerator Center (SLAC) is designed to perform a high precision investigation of the decays of the B-meson produced from electron-positron interactions. The experiment, started in May 1999, will generate approximately 300TB/year of data for 10 years. All of the data will reside in Objectivity databases accessible via the Advanced Multi-threaded Server (AMS). To date, over 70TB of data have been placed in Objectivity/DB, making it one of the largest databases in the world. Providing access to such a large quantity of data through a database server is a daunting task. A full-scale testbed environment had to be developed to tune various software parameters and a fundamental change had to occur in the AMS architecture to allow it to scale past several hundred terabytes of data. Additionally, several protocol extensions had to be implemented to provide practical access to large quantities of data. This paper will describe the design of the database and the changes that we needed to make in the AMS for scalability reasons and how the lessons we learned would be applicable to virtually any kind of database server seeking to operate in the Petabyte region.

  19. Histotripsy Liquefaction of Large Hematomas.

    Science.gov (United States)

    Khokhlova, Tatiana D; Monsky, Wayne L; Haider, Yasser A; Maxwell, Adam D; Wang, Yak-Nam; Matula, Thomas J

    2016-07-01

    Intra- and extra-muscular hematomas result from repetitive injury as well as sharp and blunt limb trauma. The clinical consequences can be serious, including debilitating pain and functional deficit. There are currently no short-term treatment options for large hematomas, only lengthy conservative treatment. The goal of this work was to evaluate the feasibility of a high intensity focused ultrasound (HIFU)-based technique, termed histotripsy, for rapid (within a clinically relevant timeframe of 15-20 min) liquefaction of large volume (up to 20 mL) extra-vascular hematomas for subsequent fine-needle aspiration. Experiments were performed using in vitro extravascular hematoma phantoms-fresh bovine blood poured into 50 mL molds and allowed to clot. The resulting phantoms were treated by boiling histotripsy (BH), cavitation histotripsy (CH) or a combination in a degassed water tank under ultrasound guidance. Two different transducers operating at 1 MHz and 1.5 MHz with f-number = 1 were used. The liquefied lysate was aspirated and analyzed by histology and sized in a Coulter Counter. The peak instantaneous power to achieve BH was lower than (at 1.5 MHz) or equal to (at 1 MHz) that which was required to initiate CH. Under the same exposure duration, BH-induced cavities were one and a half to two times larger than the CH-induced cavities, but the CH-induced cavities were more regularly shaped, facilitating easier aspiration. The lysates contained a small amount of debris larger than 70 μm, and 99% of particulates were smaller than 10 μm. A combination treatment of BH (for initial debulking) and CH (for liquefaction of small residual fragments) yielded 20 mL of lysate within 17.5 minutes of treatment and was found to be most optimal for liquefaction of large extravascular hematomas. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  20. Book review: Large igneous provinces

    Science.gov (United States)

    du Bray, Edward A.

    2015-01-01

    This book presents a comprehensive compilation of all aspects of large igneous provinces (LIPs). Published in 2014, the book is now the definitive source of information on the petrogenesis of this type of globally important, voluminous magmatic activity. In the first few pages, LIPs are characterized as magmatic provinces with areal extents >0.1 Mkm2 that are dominated by mafic magmas emplaced or erupted in intraplate settings during relatively short (1–5 m.y.) time intervals. Given these parameters, particularly areal extent, LIPs clearly represent significant contributions to global geologic evolution through time. This point is underscored, also in the introductory chapter, by a series of figures that aptly characterize the global time-space distribution of LIPs; an accompanying, particularly useful table identifies individual LIPs, quantifies their basic characteristics, and enumerates pertinent references. Accordingly, this compilation is a welcome addition to the geologic literature.

  1. Large errors and severe conditions

    CERN Document Server

    Smith, D L; Van Wormer, L A

    2002-01-01

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probabil...

  2. Large shaft development test plan

    International Nuclear Information System (INIS)

    Krug, A.D.

    1984-03-01

    This test plan proposes the conduct of shaft liner tests as part of the large shaft development test proposed for the Hanford Site in support of the repository development program. The objectives of these tests are to develop techniques for measuring liner alignment (straightness), both construction assembly alignment and downhole cumulative alignment, and to assess the alignment information as a real time feedback to aid the installation procedure. The test plan is based upon installing a 16 foot ID shaft liner into a 20 foot diameter shaft to a depth of 1000 feet. This test plan is considered to be preliminary in that it was prepared as input for the decision to determine if development testing is required in this area. Should the decision be made to proceed with development testing, this test plan shall be updated and revised. 6 refs., 2 figs

  3. Large scale biomimetic membrane arrays

    DEFF Research Database (Denmark)

    Hansen, Jesper Søndergaard; Perry, Mark; Vogel, Jörg

    2009-01-01

    To establish planar biomimetic membranes across large scale partition aperture arrays, we created a disposable single-use horizontal chamber design that supports combined optical-electrical measurements. Functional lipid bilayers could easily and efficiently be established across CO2 laser micro......-structured 8 x 8 aperture partition arrays with average aperture diameters of 301 +/- 5 mu m. We addressed the electro-physical properties of the lipid bilayers established across the micro-structured scaffold arrays by controllable reconstitution of biotechnological and physiological relevant membrane...... peptides and proteins. Next, we tested the scalability of the biomimetic membrane design by establishing lipid bilayers in rectangular 24 x 24 and hexagonal 24 x 27 aperture arrays, respectively. The results presented show that the design is suitable for further developments of sensitive biosensor assays...

  4. Model of large pool fires

    Energy Technology Data Exchange (ETDEWEB)

    Fay, J.A. [Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)]. E-mail: jfay@mit.edu

    2006-08-21

    A two zone entrainment model of pool fires is proposed to depict the fluid flow and flame properties of the fire. Consisting of combustion and plume zones, it provides a consistent scheme for developing non-dimensional scaling parameters for correlating and extrapolating pool fire visible flame length, flame tilt, surface emissive power, and fuel evaporation rate. The model is extended to include grey gas thermal radiation from soot particles in the flame zone, accounting for emission and absorption in both optically thin and thick regions. A model of convective heat transfer from the combustion zone to the liquid fuel pool, and from a water substrate to cryogenic fuel pools spreading on water, provides evaporation rates for both adiabatic and non-adiabatic fires. The model is tested against field measurements of large scale pool fires, principally of LNG, and is generally in agreement with experimental values of all variables.

  5. Model of large pool fires

    International Nuclear Information System (INIS)

    Fay, J.A.

    2006-01-01

    A two zone entrainment model of pool fires is proposed to depict the fluid flow and flame properties of the fire. Consisting of combustion and plume zones, it provides a consistent scheme for developing non-dimensional scaling parameters for correlating and extrapolating pool fire visible flame length, flame tilt, surface emissive power, and fuel evaporation rate. The model is extended to include grey gas thermal radiation from soot particles in the flame zone, accounting for emission and absorption in both optically thin and thick regions. A model of convective heat transfer from the combustion zone to the liquid fuel pool, and from a water substrate to cryogenic fuel pools spreading on water, provides evaporation rates for both adiabatic and non-adiabatic fires. The model is tested against field measurements of large scale pool fires, principally of LNG, and is generally in agreement with experimental values of all variables

  6. Large-scale solar heating

    Energy Technology Data Exchange (ETDEWEB)

    Tolonen, J.; Konttinen, P.; Lund, P. [Helsinki Univ. of Technology, Otaniemi (Finland). Advanced Energy Systems

    1998-10-01

    Solar heating market is growing in many European countries and annually installed collector area has exceeded one million square meters. There are dozens of collector manufacturers and hundreds of firms making solar heating installations in Europe. One tendency in solar heating is towards larger systems. These can be roof integrated, consisting of some tens or hundreds of square meters of collectors, or they can be larger centralized solar district heating plants consisting of a few thousand square meters of collectors. The increase of size can reduce the specific investments of solar heating systems, because e.g. the costs of some components (controllers, pumps, and pipes), planning and installation can be smaller in larger systems. The solar heat output can also be higher in large systems, because more advanced technique is economically viable

  7. Large aspect ratio tokamak study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Sardella, C.; Wiseman, G.W.

    1979-01-01

    The Large Aspect Ratio Tokamak Study (LARTS) investigated the potential for producing a viable long burn tokamak reactor through enhanced volt-second capability of the ohmic heating transformer by employing high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were accessed in the context of extended burn operation. Plasma startup and burn parameters were addressed using a one-dimensional transport code. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the field in the ohmic heating coil and the wave shape of the ohmic heating discharge. A high aspect ratio reference reactor was chosen and configured

  8. LARGE BLOCK TEST STATUS REPORT

    International Nuclear Information System (INIS)

    D.G. WILDER, W. LIN, S.C. BLAIR, T. BUSCHECK, R.C. CARLSON, K. LEE, A. MEIKE, A.L. RAMIREZ, J.L. WAGONER, AND J. WANG

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved. The United States Department of Energy (DOE) is investigatinq the suitability of Yucca Mountain (YM) as a potential site for the nation's first high-level nuclear waste repository. As shown in Fig. 1-1, the site is located about 120 km northwest of Las Vegas, Nevada, in an area of uninhabited desert

  9. Large Aperture Electrostatic Dust Detector

    International Nuclear Information System (INIS)

    Skinner, C.H.; Hensley, R.; Roquemore, A.L.

    2007-01-01

    Diagnosis and management of dust inventories generated in next-step magnetic fusion devices is necessary for their safe operation. A novel electrostatic dust detector, based on a fine grid of interlocking circuit traces biased to 30 or 50 v has been developed for the detection of dust particles on remote surfaces in air and vacuum environments. Impinging dust particles create a temporary short circuit and the resulting current pulse is recorded by counting electronics. Up to 90% of the particles are ejected from the grid or vaporized suggesting the device may be useful for controlling dust inventories. We report measurements of the sensitivity of a large area (5x5 cm) detector to microgram quantities of dust particles and review its applications to contemporary tokamaks and ITER.

  10. Conference on Large Scale Optimization

    CERN Document Server

    Hearn, D; Pardalos, P

    1994-01-01

    On February 15-17, 1993, a conference on Large Scale Optimization, hosted by the Center for Applied Optimization, was held at the University of Florida. The con­ ference was supported by the National Science Foundation, the U. S. Army Research Office, and the University of Florida, with endorsements from SIAM, MPS, ORSA and IMACS. Forty one invited speakers presented papers on mathematical program­ ming and optimal control topics with an emphasis on algorithm development, real world applications and numerical results. Participants from Canada, Japan, Sweden, The Netherlands, Germany, Belgium, Greece, and Denmark gave the meeting an important international component. At­ tendees also included representatives from IBM, American Airlines, US Air, United Parcel Serice, AT & T Bell Labs, Thinking Machines, Army High Performance Com­ puting Research Center, and Argonne National Laboratory. In addition, the NSF sponsored attendance of thirteen graduate students from universities in the United States and abro...

  11. Large scale nuclear structure studies

    International Nuclear Information System (INIS)

    Faessler, A.

    1985-01-01

    Results of large scale nuclear structure studies are reported. The starting point is the Hartree-Fock-Bogoliubov solution with angular momentum and proton and neutron number projection after variation. This model for number and spin projected two-quasiparticle excitations with realistic forces yields in sd-shell nuclei similar good results as the 'exact' shell-model calculations. Here the authors present results for a pf-shell nucleus 46 Ti and results for the A=130 mass region where they studied 58 different nuclei with the same single-particle energies and the same effective force derived from a meson exchange potential. They carried out a Hartree-Fock-Bogoliubov variation after mean field projection in realistic model spaces. In this way, they determine for each yrast state the optimal mean Hartree-Fock-Bogoliubov field. They apply this method to 130 Ce and 128 Ba using the same effective nucleon-nucleon interaction. (Auth.)

  12. Analysis of large urban fires

    International Nuclear Information System (INIS)

    Kang, S.W.; Reitter, T.A.; Takata, A.N.

    1984-11-01

    Fires in urban areas caused by a nuclear burst are analyzed as a first step towards determining their smoke-generation chacteristics, which may have grave implications for global-scale climatic consequences. A chain of events and their component processes which would follow a nuclear attack are described. A numerical code is currently being developed to calculate ultimately the smoke production rate for a given attack scenario. Available models for most of the processes are incorporated into the code. Sample calculations of urban fire-development history performed in the code for an idealized uniform city are presented. Preliminary results indicate the importance of the wind, thermal radiation transmission, fuel distributions, and ignition thresholds on the urban fire spread characteristics. Future plans are to improve the existing models and develop new ones to characterize smoke production from large urban fires. 21 references, 18 figures

  13. Large-scale river regulation

    International Nuclear Information System (INIS)

    Petts, G.

    1994-01-01

    Recent concern over human impacts on the environment has tended to focus on climatic change, desertification, destruction of tropical rain forests, and pollution. Yet large-scale water projects such as dams, reservoirs, and inter-basin transfers are among the most dramatic and extensive ways in which our environment has been, and continues to be, transformed by human action. Water running to the sea is perceived as a lost resource, floods are viewed as major hazards, and wetlands are seen as wastelands. River regulation, involving the redistribution of water in time and space, is a key concept in socio-economic development. To achieve water and food security, to develop drylands, and to prevent desertification and drought are primary aims for many countries. A second key concept is ecological sustainability. Yet the ecology of rivers and their floodplains is dependent on the natural hydrological regime, and its related biochemical and geomorphological dynamics. (Author)

  14. Large-order perturbation theory

    International Nuclear Information System (INIS)

    Wu, T.T.

    1982-01-01

    The original motivation for studying the asymptotic behavior of the coefficients of perturbation series came from quantum field theory. An overview is given of some of the attempts to understand quantum field theory beyond finite-order perturbation series. At least is the case of the Thirring model and probably in general, the full content of a relativistic quantum field theory cannot be recovered from its perturbation series. This difficulty, however, does not occur in quantum mechanics, and the anharmonic oscillator is used to illustrate the methods used in large-order perturbation theory. Two completely different methods are discussed, the first one using the WKB approximation, and a second one involving the statistical analysis of Feynman diagrams. The first one is well developed and gives detailed information about the desired asymptotic behavior, while the second one is still in its infancy and gives instead information about the distribution of vertices of the Feynman diagrams

  15. Great expectations: large wind turbines

    International Nuclear Information System (INIS)

    De Vries, E.

    2001-01-01

    This article focuses on wind turbine product development, and traces the background to wind turbines from the first generation 1.5 MW machines in 1995-6, plans for the second generation 3-5 MW class turbines to meet the expected boom in offshore wind projects, to the anticipated installation of a 4.5 MW turbine, and offshore wind projects planned for 2000-2002. The switch by the market leader Vestas to variable speed operation in 2000, the new product development and marketing strategy taken by the German Pro + Pro consultancy in their design of a 1.5 MW variable speed pitch control concept, the possible limiting of the size of turbines due to logistical difficulties, opportunities offered by air ships for large turbines, and the commissioning of offshore wind farms are discussed. Details of some 2-5 MW offshore wind turbine design specifications are tabulated

  16. Perspectives on large linear colliders

    International Nuclear Information System (INIS)

    Richter, B.

    1987-11-01

    Three main items in the design of large linear colliders are presented. The first is the interrelation of energy and luminosity requirements. These two items impose severe constraints on the accelerator builder who must design a machine to meet the needs of experimentl high energy physics rather than designing a machine for its own sake. An introduction is also given for linear collider design, concentrating on what goes on at the collision point, for still another constraint comes here from the beam-beam interaction which further restricts the choices available to the accelerator builder. The author also gives his impressions of the state of the technology available for building these kinds of machines within the next decade. The paper concludes with a brief recommendation for how we can all get on with the work faster, and hope to realize these machines sooner by working together. 10 refs., 9 figs

  17. Joint studies on large CANDU

    International Nuclear Information System (INIS)

    Lee, Ikhwan; Yu, S. K. W.

    1994-01-01

    from economic, safety and strategic viewpoints. A large number of research and development programs are now in place at AECL and KAERI that will permit substantial improvements to be realized in the next generation of CANDU okabts, Furthermore, opportunities exist for engineered improvements based on the research and development in advancing the generic CANDU Technology. Final Large CANDU joint study report with technical deliverables will be issued 1994 October. Phase 2 R and D program of the joint studies will be determined this year and implemented in next year. CANDU neutron economy permits versatility in choices of fuel cycles. This allows a utility to choose fuel cycle options for lower fuelling cost, better security of supply, and ultimately for much lower spent-fuel volume, than with PWR's alone. To meet Korea's strategic requirements, CANDU should be an integral part of the electricity supply mix.

  18. Large Volcanic Rises on Venus

    Science.gov (United States)

    Smrekar, Suzanne E.; Kiefer, Walter S.; Stofan, Ellen R.

    1997-01-01

    Large volcanic rises on Venus have been interpreted as hotspots, or the surface manifestation of mantle upwelling, on the basis of their broad topographic rises, abundant volcanism, and large positive gravity anomalies. Hotspots offer an important opportunity to study the behavior of the lithosphere in response to mantle forces. In addition to the four previously known hotspots, Atla, Bell, Beta, and western Eistla Regiones, five new probable hotspots, Dione, central Eistla, eastern Eistla, Imdr, and Themis, have been identified in the Magellan radar, gravity and topography data. These nine regions exhibit a wider range of volcano-tectonic characteristics than previously recognized for venusian hotspots, and have been classified as rift-dominated (Atla, Beta), coronae-dominated (central and eastern Eistla, Themis), or volcano-dominated (Bell, Dione, western Eistla, Imdr). The apparent depths of compensation for these regions ranges from 65 to 260 km. New estimates of the elastic thickness, using the 90 deg and order spherical harmonic field, are 15-40 km at Bell Regio, and 25 km at western Eistla Regio. Phillips et al. find a value of 30 km at Atla Regio. Numerous models of lithospheric and mantle behavior have been proposed to interpret the gravity and topography signature of the hotspots, with most studies focusing on Atla or Beta Regiones. Convective models with Earth-like parameters result in estimates of the thickness of the thermal lithosphere of approximately 100 km. Models of stagnant lid convection or thermal thinning infer the thickness of the thermal lithosphere to be 300 km or more. Without additional constraints, any of the model fits are equally valid. The thinner thermal lithosphere estimates are most consistent with the volcanic and tectonic characteristics of the hotspots. Estimates of the thermal gradient based on estimates of the elastic thickness also support a relatively thin lithosphere (Phillips et al.). The advantage of larger estimates of

  19. Reviving large-scale projects

    International Nuclear Information System (INIS)

    Desiront, A.

    2003-01-01

    For the past decade, most large-scale hydro development projects in northern Quebec have been put on hold due to land disputes with First Nations. Hydroelectric projects have recently been revived following an agreement signed with Aboriginal communities in the province who recognized the need to find new sources of revenue for future generations. Many Cree are working on the project to harness the waters of the Eastmain River located in the middle of their territory. The work involves building an 890 foot long dam, 30 dikes enclosing a 603 square-km reservoir, a spillway, and a power house with 3 generating units with a total capacity of 480 MW of power for start-up in 2007. The project will require the use of 2,400 workers in total. The Cree Construction and Development Company is working on relations between Quebec's 14,000 Crees and the James Bay Energy Corporation, the subsidiary of Hydro-Quebec which is developing the project. Approximately 10 per cent of the $735-million project has been designated for the environmental component. Inspectors ensure that the project complies fully with environmental protection guidelines. Total development costs for Eastmain-1 are in the order of $2 billion of which $735 million will cover work on site and the remainder will cover generating units, transportation and financial charges. Under the treaty known as the Peace of the Braves, signed in February 2002, the Quebec government and Hydro-Quebec will pay the Cree $70 million annually for 50 years for the right to exploit hydro, mining and forest resources within their territory. The project comes at a time when electricity export volumes to the New England states are down due to growth in Quebec's domestic demand. Hydropower is a renewable and non-polluting source of energy that is one of the most acceptable forms of energy where the Kyoto Protocol is concerned. It was emphasized that large-scale hydro-electric projects are needed to provide sufficient energy to meet both

  20. Large Scale Glazed Concrete Panels

    DEFF Research Database (Denmark)

    Bache, Anja Margrethe

    2010-01-01

    Today, there is a lot of focus on concrete surface’s aesthitic potential, both globally and locally. World famous architects such as Herzog De Meuron, Zaha Hadid, Richard Meyer and David Chippenfield challenge the exposure of concrete in their architecture. At home, this trend can be seen...... in the crinkly façade of DR-Byen (the domicile of the Danish Broadcasting Company) by architect Jean Nouvel and Zaha Hadid’s Ordrupgård’s black curved smooth concrete surfaces. Furthermore, one can point to initiatives such as “Synlig beton” (visible concrete) that can be seen on the website www.......synligbeton.dk and spæncom’s aesthetic relief effects by the designer Line Kramhøft (www.spaencom.com). It is my hope that the research-development project “Lasting large scale glazed concrete formwork,” I am working on at DTU, department of Architectural Engineering will be able to complement these. It is a project where I...

  1. The Large Hadron Collider project

    CERN Document Server

    Maiani, Luciano

    1999-01-01

    Knowledge of the fundamental constituents of matter has greatly advanced, over the last decades. The standard theory of fundamental interactions presents us with a theoretically sound picture, which describes with great accuracy known physical phenomena on most diverse energy and distance scales. These range from 10/sup -16/ cm, inside the nucleons, up to large-scale astrophysical bodies, including the early Universe at some nanosecond after the Big-Bang and temperatures of the order of 10/sup 2/ GeV. The picture is not yet completed, however, as we lack the observation of the Higgs boson, predicted in the 100-500 GeV range-a particle associated with the generation of particle masses and with the quantum fluctuations in the primordial Universe. In addition, the standard theory is expected to undergo a change of regime in the 10/sup 3/ GeV region, with the appearance of new families of particles, most likely associated with the onset of a new symmetry (supersymmetry). In 1994, the CERN Council approved the con...

  2. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  3. Large-area photonic crystals

    Science.gov (United States)

    Ruhl, Tilmann; Spahn, Peter; Hellmann, Gotz P.; Winkler, Holger

    2004-09-01

    Materials with a periodically modulated refractive index, with periods on the scale of light wavelengths, are currently attracting much attention because of their unique optical properties which are caused by Bragg scattering of the visible light. In nature, 3d structures of this kind are found in the form of opals in which monodisperse silica spheres with submicron diameters form a face-centered-cubic (fcc) lattice. Artificial opals, with the same colloidal-crystalline fcc structure, have meanwhile been prepared by crystallizing spherical colloidal particles via sedimentation or drying of dispersions. In this report, colloidal crystalline films are introduced that were produced by a novel technique based on shear flow in the melts of specially designed submicroscopic silica-polymer core-shell hybrid spheres: when the melt of these spheres flows between the plates of a press, the spheres crystallize along the plates, layer by layer, and the silica cores assume the hexagonal order corresponding to the (111) plane of the fcc lattice. This process is fast and yields large-area films, thin or thick. To enhance the refractive index contrast in these films, the colloidal crystalline structure was inverted by etching out the silica cores with hydrofluoric acid. This type of an inverse opal, in which the fcc lattice is formed by mesopores, is referred to as a polymer-air photonic crystal.

  4. Shutdown problems in large tokamaks

    International Nuclear Information System (INIS)

    Weldon, D.M.

    1978-01-01

    Some of the problems connected with a normal shutdown at the end of the burn phase (soft shutdown) and with a shutdown caused by disruptive instability (hard shutdown) have been considered. For a soft shutdown a cursory literature search was undertaken and methods for controlling the thermal wall loading were listed. Because shutdown computer codes are not widespread, some of the differences between start-up codes and shutdown codes were discussed along with program changes needed to change a start-up code to a shutdown code. For a hard shutdown, the major problems are large induced voltages in the ohmic-heating and equilibrium-field coils and high first wall erosion. A literature search of plasma-wall interactions was carried out. Phenomena that occur at the plasma-wall interface can be quite complicated. For example, material evaporated from the wall can form a virtual limiter or shield protecting the wall from major damage. Thermal gradients that occur during the interaction can produce currents whose associated magnetic field also helps shield the wall

  5. Large scale cross hole testing

    International Nuclear Information System (INIS)

    Ball, J.K.; Black, J.H.; Doe, T.

    1991-05-01

    As part of the Site Characterisation and Validation programme the results of the large scale cross hole testing have been used to document hydraulic connections across the SCV block, to test conceptual models of fracture zones and obtain hydrogeological properties of the major hydrogeological features. The SCV block is highly heterogeneous. This heterogeneity is not smoothed out even over scales of hundreds of meters. Results of the interpretation validate the hypothesis of the major fracture zones, A, B and H; not much evidence of minor fracture zones is found. The uncertainty in the flow path, through the fractured rock, causes sever problems in interpretation. Derived values of hydraulic conductivity were found to be in a narrow range of two to three orders of magnitude. Test design did not allow fracture zones to be tested individually. This could be improved by testing the high hydraulic conductivity regions specifically. The Piezomac and single hole equipment worked well. Few, if any, of the tests ran long enough to approach equilibrium. Many observation boreholes showed no response. This could either be because there is no hydraulic connection, or there is a connection but a response is not seen within the time scale of the pumping test. The fractional dimension analysis yielded credible results, and the sinusoidal testing procedure provided an effective means of identifying the dominant hydraulic connections. (10 refs.) (au)

  6. Mapping change in large networks.

    Directory of Open Access Journals (Sweden)

    Martin Rosvall

    2010-01-01

    Full Text Available Change is a fundamental ingredient of interaction patterns in biology, technology, the economy, and science itself: Interactions within and between organisms change; transportation patterns by air, land, and sea all change; the global financial flow changes; and the frontiers of scientific research change. Networks and clustering methods have become important tools to comprehend instances of these large-scale structures, but without methods to distinguish between real trends and noisy data, these approaches are not useful for studying how networks change. Only if we can assign significance to the partitioning of single networks can we distinguish meaningful structural changes from random fluctuations. Here we show that bootstrap resampling accompanied by significance clustering provides a solution to this problem. To connect changing structures with the changing function of networks, we highlight and summarize the significant structural changes with alluvial diagrams and realize de Solla Price's vision of mapping change in science: studying the citation pattern between about 7000 scientific journals over the past decade, we find that neuroscience has transformed from an interdisciplinary specialty to a mature and stand-alone discipline.

  7. Tipping device for large components

    International Nuclear Information System (INIS)

    Guigon, J.P.; Beraudier, D.

    1984-01-01

    For large components machining as components of a pressurized water reactor, it is necessary to have means allowing to present them in a position determined with regard to the machine tool used. The aim of the invention is a tipping device which consists of a base resting on the ground, a support-table mounted on this base, moving in rotation with the aid of at least a pivot joint of which axis is horizontal and parallel to the table and a gear pivot allowing to get a very good precision for the orientation of the piece and a very good stability whatever the orientation may be. The output shaft pinion of the base meshes with a gear wheel segment fixed to the table structure. Safety straps fasten the table structure to the base, as they are secured by horizontal pins. The toe pins run in straight slot holes incorporated in base jaws. The table rotation may be controlled by a spring-loaded braking mechanism which acts on the pivot axis and can be released by a hydraulic jack. The hydraulic pressure is used to prevent motor operation, unless the brakes have been released [fr

  8. Natural Selection in Large Populations

    Science.gov (United States)

    Desai, Michael

    2011-03-01

    I will discuss theoretical and experimental approaches to the evolutionary dynamics and population genetics of natural selection in large populations. In these populations, many mutations are often present simultaneously, and because recombination is limited, selection cannot act on them all independently. Rather, it can only affect whole combinations of mutations linked together on the same chromosome. Methods common in theoretical population genetics have been of limited utility in analyzing this coupling between the fates of different mutations. In the past few years it has become increasingly clear that this is a crucial gap in our understanding, as sequence data has begun to show that selection appears to act pervasively on many linked sites in a wide range of populations, including viruses, microbes, Drosophila, and humans. I will describe approaches that combine analytical tools drawn from statistical physics and dynamical systems with traditional methods in theoretical population genetics to address this problem, and describe how experiments in budding yeast can help us directly observe these evolutionary dynamics.

  9. Assembly considerations for large reflectors

    Science.gov (United States)

    Bush, H.

    1988-01-01

    The technologies developed at LaRC in the area of erectable instructures are discussed. The information is of direct value to the Large Deployable Reflector (LDR) because an option for the LDR backup structure is to assemble it in space. The efforts in this area, which include development of joints, underwater assembly simulation tests, flight assembly/disassembly tests, and fabrication of 5-meter trusses, led to the use of the LaRC concept as the baseline configuration for the Space Station Structure. The Space Station joint is linear in the load and displacement range of interest to Space Station; the ability to manually assemble and disassemble a 45-foot truss structure was demonstrated by astronauts in space as part of the ACCESS Shuttle Flight Experiment. The structure was built in 26 minutes 46 seconds, and involved a total of 500 manipulations of untethered hardware. Also, the correlation of the space experience with the neutral buoyancy simulation was very good. Sections of the proposed 5-meter bay Space Station truss have been built on the ground. Activities at LaRC have included the development of mobile remote manipulator systems (which can traverse the Space Station 5-meter structure), preliminary LDR sun shield concepts, LDR construction scenarios, and activities in robotic assembly of truss-type structures.

  10. Large superconducting coil fabrication development

    International Nuclear Information System (INIS)

    Brown, R.L.; Allred, E.L.; Anderson, W.C.; Burn, P.B.; Deaderick, R.I.; Henderson, G.M.; Marguerat, E.F.

    1975-01-01

    Toroidal fields for some fusion devices will be produced by an array of large superconducting coils. Their size, space limitation, and field requirements dictate that they be high performance coils. Once installed, accessibility for maintenance and repairs is severely restricted; therefore, good reliability is an obvious necessity. Sufficient coil fabrication will be undertaken to develop and test methods that are reliable, fast, and economical. Industrial participation will be encouraged from the outset to insure smooth transition from development phases to production phases. Initially, practice equipment for three meter bore circular coils will be developed. Oval shape coil forms will be included in the practice facility later. Equipment that is more automated will be developed with the expectation of winding faster and obtaining good coil quality. Alternate types of coil construction, methods of winding and insulating, will be investigated. Handling and assembly problems will be studied. All technology developed must be feasible for scaling up when much larger coils are needed. Experimental power reactors may need coils having six meter or larger bores

  11. Large earthquakes and creeping faults

    Science.gov (United States)

    Harris, Ruth A.

    2017-01-01

    Faults are ubiquitous throughout the Earth's crust. The majority are silent for decades to centuries, until they suddenly rupture and produce earthquakes. With a focus on shallow continental active-tectonic regions, this paper reviews a subset of faults that have a different behavior. These unusual faults slowly creep for long periods of time and produce many small earthquakes. The presence of fault creep and the related microseismicity helps illuminate faults that might not otherwise be located in fine detail, but there is also the question of how creeping faults contribute to seismic hazard. It appears that well-recorded creeping fault earthquakes of up to magnitude 6.6 that have occurred in shallow continental regions produce similar fault-surface rupture areas and similar peak ground shaking as their locked fault counterparts of the same earthquake magnitude. The behavior of much larger earthquakes on shallow creeping continental faults is less well known, because there is a dearth of comprehensive observations. Computational simulations provide an opportunity to fill the gaps in our understanding, particularly of the dynamic processes that occur during large earthquake rupture and arrest.

  12. Pressing technology for large bottoms

    International Nuclear Information System (INIS)

    Jilek, L.

    1986-01-01

    The technology has been selected of a circular plate bent into the shape of a trough, for pressing bottoms of pressure vessels from a circular plate of large diameter. The initial sheet is first bent in the middle by heating with the edges remaining straight. These are then welded longitudinally by electroslag welding and the circular shape is flame cut. The result will be a plate with a straight surface in the middle with raised edges which may be pressed into the desired shape. In this manner it is also possible to press pressure vessel bottoms with tube couplings from plates which are thickened in the middle and drilled; additional welding is then eliminated. Deformation from heat treatment may be avoided by the use of a fixture in the shape of a ring with a groove into which is fixed the edge of the bottom. During hardening of the bottom it will be necessary to care for the withdrawal of vapours and gases which would hamper uniform cooling. Bottom hardening with the grill and the cupola downwards has been proven. Deformation which occurs during treatment may to a certain extent be removed by calibration which cannot, however, be made without special fixtures and instruments. (J.B.)

  13. Relaxing a large cosmological constant

    International Nuclear Information System (INIS)

    Bauer, Florian; Sola, Joan; Stefancic, Hrvoje

    2009-01-01

    The cosmological constant (CC) problem is the biggest enigma of theoretical physics ever. In recent times, it has been rephrased as the dark energy (DE) problem in order to encompass a wider spectrum of possibilities. It is, in any case, a polyhedric puzzle with many faces, including the cosmic coincidence problem, i.e. why the density of matter ρ m is presently so close to the CC density ρ Λ . However, the oldest, toughest and most intriguing face of this polyhedron is the big CC problem, namely why the measured value of ρ Λ at present is so small as compared to any typical density scale existing in high energy physics, especially taking into account the many phase transitions that our Universe has undergone since the early times, including inflation. In this Letter, we propose to extend the field equations of General Relativity by including a class of invariant terms that automatically relax the value of the CC irrespective of the initial size of the vacuum energy in the early epochs. We show that, at late times, the Universe enters an eternal de Sitter stage mimicking a tiny positive cosmological constant. Thus, these models could be able to solve the big CC problem without fine-tuning and have also a bearing on the cosmic coincidence problem. Remarkably, they mimic the ΛCDM model to a large extent, but they still leave some characteristic imprints that should be testable in the next generation of experiments.

  14. The LUVOIR Large Mission Concept

    Science.gov (United States)

    O'Meara, John; LUVOIR Science and Technology Definition Team

    2018-01-01

    LUVOIR is one of four large mission concepts for which the NASA Astrophysics Division has commissioned studies by Science and Technology Definition Teams (STDTs) drawn from the astronomical community. We are currently developing two architectures: Architecture A with a 15.1 meter segmented primary mirror, and Architecture B with a 9.2 meter segmented primary mirror. Our focus in this presentation is the Architecture A LUVOIR. LUVOIR will operate at the Sun-Earth L2 point. It will be designed to support a broad range of astrophysics and exoplanet studies. The initial instruments developed for LUVOIR Architecture A include 1) a high-performance optical/NIR coronagraph with imaging and spectroscopic capability, 2) a UV imager and spectrograph with high spectral resolution and multi-object capability, 3) a high-definition wide-field optical/NIR camera, and 4) a high resolution UV/optical spectropolarimeter. LUVOIR will be designed for extreme stability to support unprecedented spatial resolution and coronagraphy. It is intended to be a long-lifetime facility that is both serviceable, upgradable, and primarily driven by guest observer science programs. In this presentation, we will describe the observatory, its instruments, and survey the transformative science LUVOIR can accomplish.

  15. Large-scale galaxy bias

    Science.gov (United States)

    Desjacques, Vincent; Jeong, Donghui; Schmidt, Fabian

    2018-02-01

    This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy statistics. We then review the excursion-set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  16. Large-scale galaxy bias

    Science.gov (United States)

    Jeong, Donghui; Desjacques, Vincent; Schmidt, Fabian

    2018-01-01

    Here, we briefly introduce the key results of the recent review (arXiv:1611.09787), whose abstract is as following. This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy (or halo) statistics. We then review the excursion set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  17. One to Large N Gradiometry

    Science.gov (United States)

    Langston, C. A.

    2017-12-01

    The seismic wave gradient tensor can be derived from a variety of field observations including measurements of the wavefield by a dense seismic array, strain meters, and rotation meters. Coupled with models of wave propagation, wave gradients along with the original wavefield can give estimates of wave attributes that can be used to infer wave propagation directions, apparent velocities, spatial amplitude behavior, and wave type. Compact geodetic arrays with apertures of 0.1 wavelength or less can be deployed to provide wavefield information at a localized spot similar to larger phased arrays with apertures of many wavelengths. Large N, spatially distributed arrays can provide detailed information over an area to detect structure changes. Key to accurate computation of spatial gradients from arrays of seismic instruments is knowledge of relative instrument responses, particularly component sensitivities and gains, along with relative sensor orientations. Array calibration has been successfully performed for the 14-element Pinyon Flat, California, broadband array using long-period teleseisms to achieve relative precisions as small as 0.2% in amplitude and 0.35o in orientation. Calibration has allowed successful comparison of horizontal seismic strains from local and regional seismic events with the Plate Boundary Observatory (PBO) borehole strainmeter located at the facility. Strains from the borehole strainmeter in conjunction with ground velocity from a co-located seismometer are used as a "point" array in estimating wave attributes for the P-SV components of the wavefield. An effort is underway to verify the calibration of PBO strainmeters in southern California and their co-located borehole seismic sensors to create an array of point arrays for use in studies of regional wave propagation and seismic sources.

  18. Large capacity temporary visual memory

    Science.gov (United States)

    Endress, Ansgar D.; Potter, Mary C.

    2014-01-01

    Visual working memory (WM) capacity is thought to be limited to three or four items. However, many cognitive activities seem to require larger temporary memory stores. Here, we provide evidence for a temporary memory store with much larger capacity than past WM capacity estimates. Further, based on previous WM research, we show that a single factor — proactive interference — is sufficient to bring capacity estimates down to the range of previous WM capacity estimates. Participants saw a rapid serial visual presentation (RSVP) of 5 to 21 pictures of familiar objects or words presented at rates of 4/s or 8/s, respectively, and thus too fast for strategies such as rehearsal. Recognition memory was tested with a single probe item. When new items were used on all trials, no fixed memory capacities were observed, with estimates of up to 9.1 retained pictures for 21-item lists, and up to 30.0 retained pictures for 100-item lists, and no clear upper bound to how many items could be retained. Further, memory items were not stored in a temporally stable form of memory, but decayed almost completely after a few minutes. In contrast, when, as in most WM experiments, a small set of items was reused across all trials, thus creating proactive interference among items, capacity remained in the range reported in previous WM experiments. These results show that humans have a large-capacity temporary memory store in the absence of proactive interference, and raise the question of whether temporary memory in everyday cognitive processing is severely limited as in WM experiments, or has the much larger capacity found in the present experiments. PMID:23937181

  19. Seismic analysis of large pools

    Energy Technology Data Exchange (ETDEWEB)

    Dong, R.G.; Tokarz, F.J.

    1976-11-17

    Large pools for storing spent, nuclear fuel elements are being proposed to augment present storage capacity. To preserve the ability to isolate portions of these pools, a modularization requirement appears desirable. The purpose of this project was to investigate the effects of modularization on earthquake resistance and to assess the adequacy of current design methods for seismic loads. After determining probable representative pool geometries, three rectangular pool configurations, all 240 x 16 ft and 40 ft deep, were examined. One was unmodularized; two were modularized into 80 x 40 ft cells in one case and 80 x 80 ft cells in the other. Both embedded and above-ground installations for a hard site and embedded installations for an intermediate hard site were studied. It was found that modularization was unfavorable in terms of reducing the total structural load attributable to dynamic effects, principally because one or more cells could be left unfilled. The walls of unfilled cells would be subjected to significantly higher loads than the walls of a filled, unmodularized pool. Generally, embedded installations were preferable to above-ground installations, and the hard site was superior to the intermediate hard site. It was determined that Housner's theory was adequate for calculating hydrodynamic effects on spent fuel storage pools. Current design methods for seismic loads were found to be satisfactory when results from these methods were compared with those from LUSH analyses. As a design method for dynamic soil pressure, we found the Mononobe-Okabe theory, coupled with correction factors as suggested by Seed, to be acceptable. The factors we recommend for spent fuel storage pools are tabulated.

  20. Seismic analysis of large pools

    International Nuclear Information System (INIS)

    Dong, R.G.; Tokarz, F.J.

    1976-01-01

    Large pools for storing spent, nuclear fuel elements are being proposed to augment present storage capacity. To preserve the ability to isolate portions of these pools, a modularization requirement appears desirable. The purpose of this project was to investigate the effects of modularization on earthquake resistance and to assess the adequacy of current design methods for seismic loads. After determining probable representative pool geometries, three rectangular pool configurations, all 240 x 16 ft and 40 ft deep, were examined. One was unmodularized; two were modularized into 80 x 40 ft cells in one case and 80 x 80 ft cells in the other. Both embedded and above-ground installations for a hard site and embedded installations for an intermediate hard site were studied. It was found that modularization was unfavorable in terms of reducing the total structural load attributable to dynamic effects, principally because one or more cells could be left unfilled. The walls of unfilled cells would be subjected to significantly higher loads than the walls of a filled, unmodularized pool. Generally, embedded installations were preferable to above-ground installations, and the hard site was superior to the intermediate hard site. It was determined that Housner's theory was adequate for calculating hydrodynamic effects on spent fuel storage pools. Current design methods for seismic loads were found to be satisfactory when results from these methods were compared with those from LUSH analyses. As a design method for dynamic soil pressure, we found the Mononobe-Okabe theory, coupled with correction factors as suggested by Seed, to be acceptable. The factors we recommend for spent fuel storage pools are tabulated

  1. Large optics inspection, tilting, and washing stand

    Science.gov (United States)

    Ayers, Marion Jay [Brentwood, CA; Ayers, Shannon Lee [Brentwood, CA

    2010-08-24

    A large optics stand provides a risk free means of safely tilting large optics with ease and a method of safely tilting large optics with ease. The optics are supported in the horizontal position by pads. In the vertical plane the optics are supported by saddles that evenly distribute the optics weight over a large area.

  2. Large dams and risk management

    International Nuclear Information System (INIS)

    Cazelais, N.

    2003-01-01

    In July 1996, Quebec's Saguenay region was subjected to intensive rainfall which caused severe floods and uncontrolled release of several reservoirs, resulting in extensive damage to dam structures and reservoirs. The probability of occurrence for that disaster was 1:10,000. Following the disaster, the Quebec government established a dam management body entitled the Commission scientifique et technique sur la gestion des barrages, which pointed out several safety shortcomings of existing dams. Many were either very old or had undergone significant function change without being subsequently re-evaluated. A report by the Commission stated that damage following the floods could have been limited if the design and operating standards of the dams had been more stringent. A Dam Safety Act was adopted by the Quebec National Assembly on May 30, 2000 following recommendations to retain safer structures. The Act demands regular reporting of operating procedures. Seismic activity was noted as being a topic that requires in-depth examination since Quebec's St. Lawrence Valley, particularly the Charlevoix region, is one of Canada's largest seismic zones. The other is on the west coast in British Columbia. Earthquakes in Quebec are less intense than the ones in British Columbia, but they have higher frequency content which exerts a quasi-resonance wave effect which impacts roads, bridges, buildings and hydroelectric generating facilities. Hydro-Quebec is a public utility which owns 563 retaining structures, of which 228 are ranked as large dams that measure more than 15 metres high, 400 metres long and with a reservoir capacity of more than 1 million cubic metres of water. Hydro-Quebec addresses hydrological, seismic, technological and human risks through a dam safety procedure that includes structured plans for choosing best alternatives through staged exercises. Hazard levels are minimized through the adoption of emergency, prevention and alleviation measures. The utility

  3. Large truck and bus crash facts, 2010.

    Science.gov (United States)

    2012-09-01

    This annual edition of Large Truck and Bus Crash Facts contains descriptive statistics about fatal, injury, and : property damage only crashes involving large trucks and buses in 2010. Selected crash statistics on passenger : vehicles are also presen...

  4. Large truck and bus crash facts, 2012.

    Science.gov (United States)

    2014-06-01

    This annual edition of Large Truck and Bus Crash Facts contains descriptive statistics about fatal, injury, and property damage only crashes involving large trucks and buses in 2012. Selected crash statistics on passenger vehicles are also presented ...

  5. Large truck and bus crash facts, 2013.

    Science.gov (United States)

    2015-04-01

    This annual edition of Large Truck and Bus Crash Facts contains descriptive statistics about fatal, injury, and property damage only crashes involving large trucks and buses in 2013. Selected crash statistics on passenger vehicles are also presented ...

  6. Large truck and bus crash facts, 2009.

    Science.gov (United States)

    2011-10-01

    This annual edition of Large Truck and Bus Crash Facts contains descriptive statistics about fatal, injury, and : property damage only crashes involving large trucks and buses in 2009. Selected crash statistics on passenger : vehicles are also presen...

  7. Large truck and bus crash facts, 2011.

    Science.gov (United States)

    2013-10-01

    This annual edition of Large Truck and Bus Crash Facts contains descriptive statistics about fatal, injury, and : property damage only crashes involving large trucks and buses in 2011. Selected crash statistics on passenger : vehicles are also presen...

  8. Superconducting materials for large scale applications

    International Nuclear Information System (INIS)

    Dew-Hughes, D.

    1975-01-01

    Applications of superconductors capable of carrying large current densities in large-scale electrical devices are examined. Discussions are included on critical current density, superconducting materials available, and future prospects for improved superconducting materials. (JRD)

  9. Investing in a Large Stretch Press

    Science.gov (United States)

    Choate, M.; Nealson, W.; Jay, G.; Buss, W.

    1986-01-01

    Press for forming large aluminum parts from plates provides substantial economies. Study assessed advantages and disadvantages of investing in large stretch-forming press, and also developed procurement specification for press.

  10. Large-scale energy consumers pay less

    International Nuclear Information System (INIS)

    Denneman, A.

    2012-01-01

    The price of electricity in the Netherlands rose with 6 percent in the first quarter of 2012, whereas large business consumers are paying less. The natural gas price has risen with about 10 percent in the last year, both for households and for large business consumers. Meanwhile, households are paying twice as much for electricity and gas as large business consumers. [nl

  11. 27 CFR 19.915 - Large plants.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Large plants. 19.915... OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Distilled Spirits For Fuel Use Permits § 19.915 Large plants. Any person wishing to establish a large plant shall make application for and obtain an...

  12. 75 FR 73983 - Assessments, Large Bank Pricing

    Science.gov (United States)

    2010-11-30

    ... 327 RIN 3064-AD66 Assessments, Large Bank Pricing AGENCY: Federal Deposit Insurance Corporation (FDIC... Pricing. This correction clarifies that the comment period for the Assessments, Large Bank Pricing ends January 3, 2011. FOR FURTHER INFORMATION CONTACT: Lisa Ryu, Chief, Large Bank Pricing Section, Division of...

  13. 76 FR 10671 - Assessments, Large Bank Pricing

    Science.gov (United States)

    2011-02-25

    ... 327 Assessments, Large Bank Pricing; Final Rule #0;#0;Federal Register / Vol. 76 , No. 38 / Friday... Part 327 RIN 3064-AD66 Assessments, Large Bank Pricing AGENCY: Federal Deposit Insurance Corporation..., (202) 898-6796; Lisa Ryu, Chief, Large Bank Pricing Section, Division of Insurance and Research, (202...

  14. Why did humans develop a large brain?

    OpenAIRE

    Muscat Baron, Yves

    2012-01-01

    "Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

  15. Large N baryons, strong coupling theory, quarks

    International Nuclear Information System (INIS)

    Sakita, B.

    1984-01-01

    It is shown that in QCD the large N limit is the same as the static strong coupling limit. By using the static strong coupling techniques some of the results of large N baryons are derived. The results are consistent with the large N SU(6) static quark model. (author)

  16. Forecasting distribution of numbers of large fires

    Science.gov (United States)

    Haiganoush K. Preisler; Jeff Eidenshink; Stephen Howard; Robert E. Burgan

    2015-01-01

    Systems to estimate forest fire potential commonly utilize one or more indexes that relate to expected fire behavior; however they indicate neither the chance that a large fire will occur, nor the expected number of large fires. That is, they do not quantify the probabilistic nature of fire danger. In this work we use large fire occurrence information from the...

  17. Large-group psychodynamics and massive violence

    Directory of Open Access Journals (Sweden)

    Vamik D. Volkan

    2006-06-01

    Full Text Available Beginning with Freud, psychoanalytic theories concerning large groups have mainly focused on individuals' perceptions of what their large groups psychologically mean to them. This chapter examines some aspects of large-group psychology in its own right and studies psychodynamics of ethnic, national, religious or ideological groups, the membership of which originates in childhood. I will compare the mourning process in individuals with the mourning process in large groups to illustrate why we need to study large-group psychology as a subject in itself. As part of this discussion I will also describe signs and symptoms of large-group regression. When there is a threat against a large-group's identity, massive violence may be initiated and this violence in turn, has an obvious impact on public health.

  18. Ethics of large-scale change

    OpenAIRE

    Arler, Finn

    2006-01-01

      The subject of this paper is long-term large-scale changes in human society. Some very significant examples of large-scale change are presented: human population growth, human appropriation of land and primary production, the human use of fossil fuels, and climate change. The question is posed, which kind of attitude is appropriate when dealing with large-scale changes like these from an ethical point of view. Three kinds of approaches are discussed: Aldo Leopold's mountain thinking, th...

  19. Large Display Interaction Using Mobile Devices

    OpenAIRE

    Bauer, Jens

    2015-01-01

    Large displays become more and more popular, due to dropping prices. Their size and high resolution leverages collaboration and they are capable of dis- playing even large datasets in one view. This becomes even more interesting as the number of big data applications increases. The increased screen size and other properties of large displays pose new challenges to the Human- Computer-Interaction with these screens. This includes issues such as limited scalability to the number of users, diver...

  20. Large transverse momentum behavior of gauge theories

    International Nuclear Information System (INIS)

    Coquereaux, Robert; De Rafael, Eduardo.

    1977-05-01

    The large transverse momentum behavior of Compton scattering and Moeller scattering in Quantum Electrodynamics; and of elastic quark-quark scattering in Quantum Chromodynamics are examined in perturbation theory. The results strongly suggest that the large transverse momentum regime in gauge theories is governed by a differential equation of the Callan-Symanzik type with a suitable momentum dependent anomalous dimension term. An explicit solution for the quark-quark elastic scattering amplitude at large transverse momentum is given

  1. Large-scale grid management; Storskala Nettforvaltning

    Energy Technology Data Exchange (ETDEWEB)

    Langdal, Bjoern Inge; Eggen, Arnt Ove

    2003-07-01

    The network companies in the Norwegian electricity industry now have to establish a large-scale network management, a concept essentially characterized by (1) broader focus (Broad Band, Multi Utility,...) and (2) bigger units with large networks and more customers. Research done by SINTEF Energy Research shows so far that the approaches within large-scale network management may be structured according to three main challenges: centralization, decentralization and out sourcing. The article is part of a planned series.

  2. Reliability of large and complex systems

    CERN Document Server

    Kolowrocki, Krzysztof

    2014-01-01

    Reliability of Large and Complex Systems, previously titled Reliability of Large Systems, is an innovative guide to the current state and reliability of large and complex systems. In addition to revised and updated content on the complexity and safety of large and complex mechanisms, this new edition looks at the reliability of nanosystems, a key research topic in nanotechnology science. The author discusses the importance of safety investigation of critical infrastructures that have aged or have been exposed to varying operational conditions. This reference provides an asympt

  3. Implementing Large Projects in Software Engineering Courses

    Science.gov (United States)

    Coppit, David

    2006-01-01

    In software engineering education, large projects are widely recognized as a useful way of exposing students to the real-world difficulties of team software development. But large projects are difficult to put into practice. First, educators rarely have additional time to manage software projects. Second, classrooms have inherent limitations that…

  4. Asian Eden : large herbivore ecology in India

    NARCIS (Netherlands)

    Ahrestani, F.S.

    2009-01-01

    The study of large mammalian herbivore ecology has a strong allometric tradition. The
    majority of studies that have helped better understand how body mass affects large herbivore
    ecology in the tropics, from a biological, functional, and ecological perspective, are from
    Africa.

  5. The large deviation approach to statistical mechanics

    International Nuclear Information System (INIS)

    Touchette, Hugo

    2009-01-01

    The theory of large deviations is concerned with the exponential decay of probabilities of large fluctuations in random systems. These probabilities are important in many fields of study, including statistics, finance, and engineering, as they often yield valuable information about the large fluctuations of a random system around its most probable state or trajectory. In the context of equilibrium statistical mechanics, the theory of large deviations provides exponential-order estimates of probabilities that refine and generalize Einstein's theory of fluctuations. This review explores this and other connections between large deviation theory and statistical mechanics, in an effort to show that the mathematical language of statistical mechanics is the language of large deviation theory. The first part of the review presents the basics of large deviation theory, and works out many of its classical applications related to sums of random variables and Markov processes. The second part goes through many problems and results of statistical mechanics, and shows how these can be formulated and derived within the context of large deviation theory. The problems and results treated cover a wide range of physical systems, including equilibrium many-particle systems, noise-perturbed dynamics, nonequilibrium systems, as well as multifractals, disordered systems, and chaotic systems. This review also covers many fundamental aspects of statistical mechanics, such as the derivation of variational principles characterizing equilibrium and nonequilibrium states, the breaking of the Legendre transform for nonconcave entropies, and the characterization of nonequilibrium fluctuations through fluctuation relations.

  6. Large Scale Computations in Air Pollution Modelling

    DEFF Research Database (Denmark)

    Zlatev, Z.; Brandt, J.; Builtjes, P. J. H.

    Proceedings of the NATO Advanced Research Workshop on Large Scale Computations in Air Pollution Modelling, Sofia, Bulgaria, 6-10 July 1998......Proceedings of the NATO Advanced Research Workshop on Large Scale Computations in Air Pollution Modelling, Sofia, Bulgaria, 6-10 July 1998...

  7. Reflections on Teaching a Large Class.

    Science.gov (United States)

    Miner, Rick

    1992-01-01

    Uses an analysis of small- and large-class differences as a framework for planning for and teaching a large class. Analyzes the process of developing and offering an organizational behavior class to 141 college students. Suggests ways to improve teaching effectiveness by minimizing psychological and physical distances, redistributing resources,…

  8. Superconducting magnets technologies for large accelerator

    International Nuclear Information System (INIS)

    Ogitsu, Toru

    2017-01-01

    The first hadron collider with superconducting magnet technologies was built at Fermi National Accelerator Laboratory as TEVATRON. Since then, the superconducting magnet technologies are widely used in large accelerator applications. The paper summarizes the superconducting magnet technologies used for large accelerators. (author)

  9. Automating large-scale reactor systems

    International Nuclear Information System (INIS)

    Kisner, R.A.

    1985-01-01

    This paper conveys a philosophy for developing automated large-scale control systems that behave in an integrated, intelligent, flexible manner. Methods for operating large-scale systems under varying degrees of equipment degradation are discussed, and a design approach that separates the effort into phases is suggested. 5 refs., 1 fig

  10. Comb-drive actuators for large displacements

    NARCIS (Netherlands)

    Legtenberg, Rob; Legtenberg, R.; Groeneveld, A.W.; Elwenspoek, Michael Curt

    The design, fabrication and experimental results of lateral-comb-drive actuators for large displacements at low driving voltages is presented. A comparison of several suspension designs is given, and the lateral large deflection behaviour of clamped-clamped beams and a folded flexure design is

  11. Large-scale perspective as a challenge

    NARCIS (Netherlands)

    Plomp, M.G.A.

    2012-01-01

    1. Scale forms a challenge for chain researchers: when exactly is something ‘large-scale’? What are the underlying factors (e.g. number of parties, data, objects in the chain, complexity) that determine this? It appears to be a continuum between small- and large-scale, where positioning on that

  12. Computing in Large-Scale Dynamic Systems

    NARCIS (Netherlands)

    Pruteanu, A.S.

    2013-01-01

    Software applications developed for large-scale systems have always been difficult to de- velop due to problems caused by the large number of computing devices involved. Above a certain network size (roughly one hundred), necessary services such as code updating, topol- ogy discovery and data

  13. Decentralized Large-Scale Power Balancing

    DEFF Research Database (Denmark)

    Halvgaard, Rasmus; Jørgensen, John Bagterp; Poulsen, Niels Kjølstad

    2013-01-01

    problem is formulated as a centralized large-scale optimization problem but is then decomposed into smaller subproblems that are solved locally by each unit connected to an aggregator. For large-scale systems the method is faster than solving the full problem and can be distributed to include an arbitrary...

  14. Large Mines and the Community : Socioeconomic and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 janv. 2001 ... Large Mines and the Community : Socioeconomic and Environmental Effects in Latin America, Canada, and Spain. Couverture du livre Large Mines and the Community : Socioeconomic and Environmental Effects in Latin America. Directeur(s):. Gary McMahon et Felix Remy. Maison(s) d'édition: Banque ...

  15. The algebras of large N matrix mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Halpern, M.B.; Schwartz, C.

    1999-09-16

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden!) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N.

  16. The large deviation approach to statistical mechanics

    Science.gov (United States)

    Touchette, Hugo

    2009-07-01

    The theory of large deviations is concerned with the exponential decay of probabilities of large fluctuations in random systems. These probabilities are important in many fields of study, including statistics, finance, and engineering, as they often yield valuable information about the large fluctuations of a random system around its most probable state or trajectory. In the context of equilibrium statistical mechanics, the theory of large deviations provides exponential-order estimates of probabilities that refine and generalize Einstein’s theory of fluctuations. This review explores this and other connections between large deviation theory and statistical mechanics, in an effort to show that the mathematical language of statistical mechanics is the language of large deviation theory. The first part of the review presents the basics of large deviation theory, and works out many of its classical applications related to sums of random variables and Markov processes. The second part goes through many problems and results of statistical mechanics, and shows how these can be formulated and derived within the context of large deviation theory. The problems and results treated cover a wide range of physical systems, including equilibrium many-particle systems, noise-perturbed dynamics, nonequilibrium systems, as well as multifractals, disordered systems, and chaotic systems. This review also covers many fundamental aspects of statistical mechanics, such as the derivation of variational principles characterizing equilibrium and nonequilibrium states, the breaking of the Legendre transform for nonconcave entropies, and the characterization of nonequilibrium fluctuations through fluctuation relations.

  17. Efficient querying of large process model repositories

    NARCIS (Netherlands)

    Jin, Tao; Wang, Jianmin; La Rosa, M.; Hofstede, ter A.H.M.; Wen, Lijie

    2013-01-01

    Recent years have seen an increased uptake of business process management technology in industries. This has resulted in organizations trying to manage large collections of business process models. One of the challenges facing these organizations concerns the retrieval of models from large business

  18. Environmental effects and large space systems

    Science.gov (United States)

    Garrett, H. B.

    1981-01-01

    When planning large scale operations in space, environmental impact must be considered in addition to radiation, spacecraft charging, contamination, high power and size. Pollution of the atmosphere and space is caused by rocket effluents and by photoelectrons generated by sunlight falling on satellite surfaces even light pollution may result (the SPS may reflect so much light as to be a nuisance to astronomers). Large (100 Km 2) structures also will absorb the high energy particles that impinge on them. Altogether, these effects may drastically alter the Earth's magnetosphere. It is not clear if these alterations will in any way affect the Earth's surface climate. Large structures will also generate large plasma wakes and waves which may cause interference with communications to the vehicle. A high energy, microwave beam from the SPS will cause ionospheric turbulence, affecting UHF and VHF communications. Although none of these effects may ultimately prove critical, they must be considered in the design of large structures.

  19. Entanglement transitions induced by large deviations

    Science.gov (United States)

    Bhosale, Udaysinh T.

    2017-12-01

    The probability of large deviations of the smallest Schmidt eigenvalue for random pure states of bipartite systems, denoted as A and B , is computed analytically using a Coulomb gas method. It is shown that this probability, for large N , goes as exp[-β N2Φ (ζ ) ] , where the parameter β is the Dyson index of the ensemble, ζ is the large deviation parameter, while the rate function Φ (ζ ) is calculated exactly. Corresponding equilibrium Coulomb charge density is derived for its large deviations. Effects of the large deviations of the extreme (largest and smallest) Schmidt eigenvalues on the bipartite entanglement are studied using the von Neumann entropy. Effect of these deviations is also studied on the entanglement between subsystems 1 and 2, obtained by further partitioning the subsystem A , using the properties of the density matrix's partial transpose ρ12Γ. The density of states of ρ12Γ is found to be close to the Wigner's semicircle law with these large deviations. The entanglement properties are captured very well by a simple random matrix model for the partial transpose. The model predicts the entanglement transition across a critical large deviation parameter ζ . Log negativity is used to quantify the entanglement between subsystems 1 and 2. Analytical formulas for it are derived using the simple model. Numerical simulations are in excellent agreement with the analytical results.

  20. Analysis of large databases in vascular surgery.

    Science.gov (United States)

    Nguyen, Louis L; Barshes, Neal R

    2010-09-01

    Large databases can be a rich source of clinical and administrative information on broad populations. These datasets are characterized by demographic and clinical data for over 1000 patients from multiple institutions. Since they are often collected and funded for other purposes, their use for secondary analysis increases their utility at relatively low costs. Advantages of large databases as a source include the very large numbers of available patients and their related medical information. Disadvantages include lack of detailed clinical information and absence of causal descriptions. Researchers working with large databases should also be mindful of data structure design and inherent limitations to large databases, such as treatment bias and systemic sampling errors. Withstanding these limitations, several important studies have been published in vascular care using large databases. They represent timely, "real-world" analyses of questions that may be too difficult or costly to address using prospective randomized methods. Large databases will be an increasingly important analytical resource as we focus on improving national health care efficacy in the setting of limited resources.

  1. Recent quality of ultra large rotor shafts

    International Nuclear Information System (INIS)

    Suzuki, Akira; Kinoshita, Shushi; Morita, Kikuo; Kikuchi, Hideo; Takada, Masayoshi

    1983-01-01

    Large size and high quality are required for rotor shafts accompanying recent trend of thermal and nuclear power generation toward large capacity. As for the low pressure rotor shafts for large capacity turbines, the disks and a shaft tend to be made into one body instead of conventional shrink fit construction, because of the experience of rotor accidents and the improvement of reliability. Therefore the ingots required become more and more large, and excellent production techniques are required for steel making, forging and heat treatment. Kobe Steel Ltd. have made about 20 large generator shafts from 420 t and 500 t ingots, and confirmed their stable high quality. Also a one-body low pressure rotor of 2600 mm diameter was made for trial, and its quality was examined. It was confirmed that the effect of forging and heat treatment was given sufficiently, and the production techniques for super-large one-body rotors were established. In steel making, vacuum degassing was applied twice to decrease hydrogen content, and VV restriction forging and pre-stage treatment were carried out. The properties of large rotors are reported. (Kako, I.)

  2. Distributed simulation of large computer systems

    International Nuclear Information System (INIS)

    Marzolla, M.

    2001-01-01

    Sequential simulation of large complex physical systems is often regarded as a computationally expensive task. In order to speed-up complex discrete-event simulations, the paradigm of Parallel and Distributed Discrete Event Simulation (PDES) has been introduced since the late 70s. The authors analyze the applicability of PDES to the modeling and analysis of large computer system; such systems are increasingly common in the area of High Energy and Nuclear Physics, because many modern experiments make use of large 'compute farms'. Some feasibility tests have been performed on a prototype distributed simulator

  3. Large scale network-centric distributed systems

    CERN Document Server

    Sarbazi-Azad, Hamid

    2014-01-01

    A highly accessible reference offering a broad range of topics and insights on large scale network-centric distributed systems Evolving from the fields of high-performance computing and networking, large scale network-centric distributed systems continues to grow as one of the most important topics in computing and communication and many interdisciplinary areas. Dealing with both wired and wireless networks, this book focuses on the design and performance issues of such systems. Large Scale Network-Centric Distributed Systems provides in-depth coverage ranging from ground-level hardware issu

  4. The Amateurs' Love Affair with Large Datasets

    Science.gov (United States)

    Price, Aaron; Jacoby, S. H.; Henden, A.

    2006-12-01

    Amateur astronomers are professionals in other areas. They bring expertise from such varied and technical careers as computer science, mathematics, engineering, and marketing. These skills, coupled with an enthusiasm for astronomy, can be used to help manage the large data sets coming online in the next decade. We will show specific examples where teams of amateurs have been involved in mining large, online data sets and have authored and published their own papers in peer-reviewed astronomical journals. Using the proposed LSST database as an example, we will outline a framework for involving amateurs in data analysis and education with large astronomical surveys.

  5. Electronic and atomic impacts on large clusters

    International Nuclear Information System (INIS)

    Gspann, J.

    1982-01-01

    Describing first the generation and properties of molecular beams of large Van der Waals clusters such as speed distribution, cluster size distribution, and internal temperature of the clusters, the review then features the results of electronic impacts on large clusters: metastable electronic cluster excitations, ejection of positive cluster ions of less than 100 atoms from much larger parent clusters, and ionization of the large clusters. Atomic impacts at thermal energies are treated with respect to the scattering cross section of the clusters, their drag coefficient in free molecular flow, and the peculiarities of impacts on helium clusters of either isotope. (Auth.)

  6. Large polarons in lead halide perovskites

    OpenAIRE

    Miyata, Kiyoshi; Meggiolaro, Daniele; Trinh, M. Tuan; Joshi, Prakriti P.; Mosconi, Edoardo; Jones, Skyler C.; De Angelis, Filippo; Zhu, X.-Y.

    2017-01-01

    Lead halide perovskites show marked defect tolerance responsible for their excellent optoelectronic properties. These properties might be explained by the formation of large polarons, but how they are formed and whether organic cations are essential remain open questions. We provide a direct time domain view of large polaron formation in single-crystal lead bromide perovskites CH3NH3PbBr3 and CsPbBr3. We found that large polaron forms predominantly from the deformation of the PbBr3 ? framewor...

  7. Laparoscopic transperitoneal ureterolithotomy for large ureteric stones

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Sayyad

    2012-01-01

    Conclusion: Laparoscopic transperitoneal ureterolithotomy is a safe and effective approach for selected patients with large proximal ureteric stones with reduced postoperative pain and short hospital stay, and should be considered as a treatment option for such stones.

  8. Large-scale numerical simulations of plasmas

    International Nuclear Information System (INIS)

    Hamaguchi, Satoshi

    2004-01-01

    The recent trend of large scales simulations of fusion plasma and processing plasmas is briefly summarized. Many advanced simulation techniques have been developed for fusion plasmas and some of these techniques are now applied to analyses of processing plasmas. (author)

  9. Large Truck Crash Causation Study (LTCCS)

    Data.gov (United States)

    Department of Transportation — The Large Truck* Crash Causation Study (LTCCS) is based on a three-year data collection project conducted by the Federal Motor Carrier Safety Administration (FMCSA)...

  10. A large-scale study of misophonia

    NARCIS (Netherlands)

    Rouw, R.; Erfanian, M.

    2018-01-01

    Objective We aim to elucidate misophonia, a condition in which particular sounds elicit disproportionally strong aversive reactions. Method A large online study extensively surveyed personal, developmental, and clinical characteristics of over 300 misophonics. Results Most participants indicated

  11. The Expanded Very Large Array Project

    Science.gov (United States)

    Perley, Rick

    2012-10-01

    The Expanded Very Large Array Project, begun in 2001, is now completed -- on time, on budget, and ``on spec.'' The major goal of the project was to multiply the key observational capabilities of the Very Large Array -- the world's most powerful, versatile, and productive radio telescope -- by a factor of at least an order of magnitude by implementation of modern technologies. The result of the project is an operationally new telescope -- renamed the Jansky Very Large Array -- which is capable of new science unimagined in 1980, when the original VLA was completed. In this talk, I will review the goals of the project, and describe the new capabilities of the Jansky Very Large Array. Already, the array is providing fabulous new insights into the physics of the universe,and I will spend the majority of the time describing examples of new results.

  12. Nonlinear continuum mechanics and large inelastic deformations

    CERN Document Server

    Dimitrienko, Yuriy I

    2010-01-01

    This book provides a rigorous axiomatic approach to continuum mechanics under large deformation. In addition to the classical nonlinear continuum mechanics - kinematics, fundamental laws, the theory of functions having jump discontinuities across singular surfaces, etc. - the book presents the theory of co-rotational derivatives, dynamic deformation compatibility equations, and the principles of material indifference and symmetry, all in systematized form. The focus of the book is a new approach to the formulation of the constitutive equations for elastic and inelastic continua under large deformation. This new approach is based on using energetic and quasi-energetic couples of stress and deformation tensors. This approach leads to a unified treatment of large, anisotropic elastic, viscoelastic, and plastic deformations. The author analyses classical problems, including some involving nonlinear wave propagation, using different models for continua under large deformation, and shows how different models lead t...

  13. Large-scale computing with Quantum Espresso

    International Nuclear Information System (INIS)

    Giannozzi, P.; Cavazzoni, C.

    2009-01-01

    This paper gives a short introduction to Quantum Espresso: a distribution of software for atomistic simulations in condensed-matter physics, chemical physics, materials science, and to its usage in large-scale parallel computing.

  14. Swarm Manipulation of Large Surface Vessels

    National Research Council Canada - National Science Library

    Smith, Erik T

    2007-01-01

    The goal of this Trident project was to develop an independent control scheme to allow a team of autonomous tugboats to move a large disabled vessel, such as a barge, to a desired position and orientation...

  15. South African red data book - large mammals

    CSIR Research Space (South Africa)

    Skinner, JD

    1977-11-01

    Full Text Available Data sheets are provided for 22 threatened South African large mammals, one exterminated (Liechtenstein1s hartebeest), eight endangered (cheetah, hunting dog, dugong, Cape mountain zebra, black rhinoceros, tsessebe, roan antelope, suni), one...

  16. Computational Modeling of Large Wildfires: A Roadmap

    KAUST Repository

    Coen, Janice L.; Douglas, Craig C.

    2010-01-01

    Wildland fire behavior, particularly that of large, uncontrolled wildfires, has not been well understood or predicted. Our methodology to simulate this phenomenon uses high-resolution dynamic models made of numerical weather prediction (NWP) models

  17. Remotely controlled large container disposal methodology

    International Nuclear Information System (INIS)

    Amir, S.J.

    1994-09-01

    Remotely Handled Large Containers (RHLC), also called drag-off boxes, have been used at the Hanford Site since the 1940s to dispose of large pieces of radioactively contaminated equipment. These containers are typically large steel-reinforced concrete boxes, which weigh as much as 40 tons. Because large quantities of high-dose waste can produce radiation levels as high as 200 mrem/hour at 200 ft, the containers are remotely handled (either lifted off the railcar by crane or dragged off with a cable). Many of the existing containers do not meet existing structural and safety design criteria and some of the transportation requirements. The drag-off method of pulling the box off the railcar using a cable and a tractor is also not considered a safe operation, especially in view of past mishaps

  18. Large-bandwidth planar photonic crystal waveguides

    DEFF Research Database (Denmark)

    Søndergaard, Thomas; Lavrinenko, Andrei

    2002-01-01

    A general design principle is presented for making finite-height photonic crystal waveguides that support leakage-free guidance of light over large frequency intervals. The large bandwidth waveguides are designed by introducing line defects in photonic crystal slabs, where the material in the line...... defect has appropriate dispersion properties relative to the photonic crystal slab material surrounding the line defect. A three-dimensional theoretical analysis is given for large-bandwidth waveguide designs based on a silicon-air photonic crystal slab suspended in air. In one example, the leakage......-free single-mode guidance is found for a large frequency interval covering 60% of the photonic band-gap....

  19. Large Area Sputter Coating on Glass

    Science.gov (United States)

    Katayama, Yoshihito

    Large glass has been used for commercial buildings, housings and vehicles for many years. Glass size for flat displays is getting larger and larger. The glass for the 8th generation is more than 5 m2 in area. Demand of the large glass is increasing not only in these markets but also in a solar cell market growing drastically. Therefore, large area coating is demanded to plus something else on glass more than ever. Sputtering and pyrolysis are the major coating methods on large glass today. Sputtering process is particularly popular because it can deposit a wide variety of materials in good coating uniformity on the glass. This paper describes typical industrial sputtering system and recent progress in sputtering technology. It also shows typical coated glass products in architectural, automotive and display fields and comments on their functions, film stacks and so on.

  20. Large-scale regions of antimatter

    International Nuclear Information System (INIS)

    Grobov, A. V.; Rubin, S. G.

    2015-01-01

    Amodified mechanism of the formation of large-scale antimatter regions is proposed. Antimatter appears owing to fluctuations of a complex scalar field that carries a baryon charge in the inflation era

  1. Large-scale regions of antimatter

    Energy Technology Data Exchange (ETDEWEB)

    Grobov, A. V., E-mail: alexey.grobov@gmail.com; Rubin, S. G., E-mail: sgrubin@mephi.ru [National Research Nuclear University MEPhI (Russian Federation)

    2015-07-15

    Amodified mechanism of the formation of large-scale antimatter regions is proposed. Antimatter appears owing to fluctuations of a complex scalar field that carries a baryon charge in the inflation era.

  2. Innovation Initiatives in Large Software Companies

    DEFF Research Database (Denmark)

    Edison, Henry; Wang, Xiaofeng; Jabangwe, Ronald

    2018-01-01

    empirical studies on innovation initiative in the context of large software companies. A total of 7 studies are conducted in the context of large software companies, which reported 5 types of initiatives: intrapreneurship, bootlegging, internal venture, spin-off and crowdsourcing. Our study offers three......Context: To keep the competitive advantage and adapt to changes in the market and technology, companies need to innovate in an organised, purposeful and systematic manner. However, due to their size and complexity, large companies tend to focus on the structure in maintaining their business, which...... can potentially lower their agility to innovate. Objective:The aims of this study are to provide an overview of the current research on innovation initiatives and to identify the challenges of implementing those initiatives in the context of large software companies. Method: The investigation...

  3. Production of baryons with large transverse momentum

    International Nuclear Information System (INIS)

    Landshoff, P.V.; Polkinghorne, J.C.; Scott, D.M.

    1975-01-01

    The multiple scattering of constituent quarks provides a natural mechanism for fairly copious production of large-transverse-momentum baryons in nucleon--nucleon collisions. The predicted scaling law agrees well with available data, and the mechanism provides a qualitative explanation of nuclear-target effects. In comparison with previous parton models, correlations are predicted to be qualitatively different, and large-p/sub T/ baryon production by meson beams is relatively suppressed

  4. Neutrino bi-large mixings and family

    International Nuclear Information System (INIS)

    Bando, Masako; Obara, Midori

    2004-01-01

    After a brief review of quark-lepton relations in grand unified theories (GUT), we show that the Pati-Salam relation with only one type of Higgs field configuration with ''four zero symmetric texture'' can reproduce two large neutrino mixings as well as observed mass differences. This is quite in contrast to the case of SU(5) where bi-large mixings essentially come from the charged lepton sector with non-symmetric charged lepton mass matrix. (author)

  5. Cruas site: inception of 'large jobsite' procedure

    International Nuclear Information System (INIS)

    Bottini, R.

    1980-01-01

    In France, the construction sites of nuclear plants are governed by a series of government decisions approved in July 1975 relating to so-called 'large jobsites of territorial improvements'. Using as an example the 'large jobsite' of the Cruas plant, now under construction, the author illustrates the practical application of the considered procedure, amongst others from the standpoints of organization measures and the quality of the living conditions of workers [fr

  6. LYCORIS - A Large Area Strip Telescope

    CERN Document Server

    Krämer, U; Stanitzki, M; Wu, M

    2018-01-01

    The LYCORIS Large Area Silicon Strip Telescope for the DESY II Test Beam Facility is presented. The DESY II Test Beam Facility provides elec- tron and positron beams for beam tests of up to 6 GeV. A new telescope with a large 10 × 20 cm2 coverage area based on a 25 μm pitch strip sensor is to be installed within the PCMAG 1 T solenoid. The current state of the system is presented.

  7. Transport Coefficients from Large Deviation Functions

    OpenAIRE

    Gao, Chloe Ya; Limmer, David T.

    2017-01-01

    We describe a method for computing transport coefficients from the direct evaluation of large deviation functions. This method is general, relying on only equilibrium fluctuations, and is statistically efficient, employing trajectory based importance sampling. Equilibrium fluctuations of molecular currents are characterized by their large deviation functions, which are scaled cumulant generating functions analogous to the free energies. A diffusion Monte Carlo algorithm is used to evaluate th...

  8. A very large multigap resistive plate chamber

    CERN Document Server

    Cerron-Zeballos, E; Hatzifotiadou, D; Kim, D W; Lamas-Valverde, J; Lee, S C; Platner, E D; Roberts, J; Williams, M C S; Zichichi, A

    1999-01-01

    We have built and tested a very large multigap resistive plate chamber (MRPC). We discuss the suitability of the multigap RPC for the construction of large area modules. We give details of the construction technique and results from a scan across the surface of the chamber. We also report on the implementation of `half-strip resolution', where we improve the spatial resolution by a factor 2 without increasing the number of read-out channels. (9 refs).

  9. Vanishing large ovarian cyst with thyroxine therapy

    OpenAIRE

    Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

    2013-01-01

    Summary A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the cond...

  10. The large deviations theorem and ergodicity

    International Nuclear Information System (INIS)

    Gu Rongbao

    2007-01-01

    In this paper, some relationships between stochastic and topological properties of dynamical systems are studied. For a continuous map f from a compact metric space X into itself, we show that if f satisfies the large deviations theorem then it is topologically ergodic. Moreover, we introduce the topologically strong ergodicity, and prove that if f is a topologically strongly ergodic map satisfying the large deviations theorem then it is sensitively dependent on initial conditions

  11. Workflow management in large distributed systems

    International Nuclear Information System (INIS)

    Legrand, I; Newman, H; Voicu, R; Dobre, C; Grigoras, C

    2011-01-01

    The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

  12. Political consultation and large-scale research

    International Nuclear Information System (INIS)

    Bechmann, G.; Folkers, H.

    1977-01-01

    Large-scale research and policy consulting have an intermediary position between sociological sub-systems. While large-scale research coordinates science, policy, and production, policy consulting coordinates science, policy and political spheres. In this very position, large-scale research and policy consulting lack of institutional guarantees and rational back-ground guarantee which are characteristic for their sociological environment. This large-scale research can neither deal with the production of innovative goods under consideration of rentability, nor can it hope for full recognition by the basis-oriented scientific community. Policy consulting knows neither the competence assignment of the political system to make decisions nor can it judge succesfully by the critical standards of the established social science, at least as far as the present situation is concerned. This intermediary position of large-scale research and policy consulting has, in three points, a consequence supporting the thesis which states that this is a new form of institutionalization of science: These are: 1) external control, 2) the organization form, 3) the theoretical conception of large-scale research and policy consulting. (orig.) [de

  13. Workflow management in large distributed systems

    Science.gov (United States)

    Legrand, I.; Newman, H.; Voicu, R.; Dobre, C.; Grigoras, C.

    2011-12-01

    The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

  14. Large Payload Ground Transportation and Test Considerations

    Science.gov (United States)

    Rucker, Michelle A.

    2016-01-01

    Many spacecraft concepts under consideration by the National Aeronautics and Space Administration’s (NASA’s) Evolvable Mars Campaign take advantage of a Space Launch System payload shroud that may be 8 to 10 meters in diameter. Large payloads can theoretically save cost by reducing the number of launches needed--but only if it is possible to build, test, and transport a large payload to the launch site in the first place. Analysis performed previously for the Altair project identified several transportation and test issues with an 8.973 meters diameter payload. Although the entire Constellation Program—including Altair—has since been canceled, these issues serve as important lessons learned for spacecraft designers and program managers considering large payloads for future programs. A transportation feasibility study found that, even broken up into an Ascent and Descent Module, the Altair spacecraft would not fit inside available aircraft. Ground transportation of such large payloads over extended distances is not generally permitted, so overland transportation alone would not be an option. Limited ground transportation to the nearest waterway may be possible, but water transportation could take as long as 67 days per production unit, depending on point of origin and acceptance test facility; transportation from the western United States would require transit through the Panama Canal to access the Kennedy Space Center launch site. Large payloads also pose acceptance test and ground processing challenges. Although propulsion, mechanical vibration, and reverberant acoustic test facilities at NASA’s Plum Brook Station have been designed to accommodate large spacecraft, special handling and test work-arounds may be necessary, which could increase cost, schedule, and technical risk. Once at the launch site, there are no facilities currently capable of accommodating the combination of large payload size and hazardous processing such as hypergolic fuels

  15. Why large cells dominate estuarine phytoplankton

    Science.gov (United States)

    Cloern, James E.

    2018-01-01

    Surveys across the world oceans have shown that phytoplankton biomass and production are dominated by small cells (picoplankton) where nutrient concentrations are low, but large cells (microplankton) dominate when nutrient-rich deep water is mixed to the surface. I analyzed phytoplankton size structure in samples collected over 25 yr in San Francisco Bay, a nutrient-rich estuary. Biomass was dominated by large cells because their biomass selectively grew during blooms. Large-cell dominance appears to be a characteristic of ecosystems at the land–sea interface, and these places may therefore function as analogs to oceanic upwelling systems. Simulations with a size-structured NPZ model showed that runs of positive net growth rate persisted long enough for biomass of large, but not small, cells to accumulate. Model experiments showed that small cells would dominate in the absence of grazing, at lower nutrient concentrations, and at elevated (+5°C) temperatures. Underlying these results are two fundamental scaling laws: (1) large cells are grazed more slowly than small cells, and (2) grazing rate increases with temperature faster than growth rate. The model experiments suggest testable hypotheses about phytoplankton size structure at the land–sea interface: (1) anthropogenic nutrient enrichment increases cell size; (2) this response varies with temperature and only occurs at mid-high latitudes; (3) large-cell blooms can only develop when temperature is below a critical value, around 15°C; (4) cell size diminishes along temperature gradients from high to low latitudes; and (5) large-cell blooms will diminish or disappear where planetary warming increases temperature beyond their critical threshold.

  16. Dissecting the large-scale galactic conformity

    Science.gov (United States)

    Seo, Seongu

    2018-01-01

    Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

  17. Evolution and interaction of large interplanetary streams

    International Nuclear Information System (INIS)

    Whang, Y.C.; Burlaga, L.F.

    1985-02-01

    A computer simulation for the evolution and interaction of large interplanetary streams based on multi-spacecraft observations and an unsteady, one-dimensional MHD model is presented. Two events, each observed by two or more spacecraft separated by a distance of the order of 10 AU, were studied. The first simulation is based on the plasma and magnetic field observations made by two radially-aligned spacecraft. The second simulation is based on an event observed first by Helios-1 in May 1980 near 0.6 AU and later by Voyager-1 in June 1980 at 8.1 AU. These examples show that the dynamical evolution of large-scale solar wind structures is dominated by the shock process, including the formation, collision, and merging of shocks. The interaction of shocks with stream structures also causes a drastic decrease in the amplitude of the solar wind speed variation with increasing heliocentric distance, and as a result of interactions there is a large variation of shock-strengths and shock-speeds. The simulation results shed light on the interpretation for the interaction and evolution of large interplanetary streams. Observations were made along a few limited trajectories, but simulation results can supplement these by providing the detailed evolution process for large-scale solar wind structures in the vast region not directly observed. The use of a quantitative nonlinear simulation model including shock merging process is crucial in the interpretation of data obtained in the outer heliosphere

  18. Large-scale multimedia modeling applications

    International Nuclear Information System (INIS)

    Droppo, J.G. Jr.; Buck, J.W.; Whelan, G.; Strenge, D.L.; Castleton, K.J.; Gelston, G.M.

    1995-08-01

    Over the past decade, the US Department of Energy (DOE) and other agencies have faced increasing scrutiny for a wide range of environmental issues related to past and current practices. A number of large-scale applications have been undertaken that required analysis of large numbers of potential environmental issues over a wide range of environmental conditions and contaminants. Several of these applications, referred to here as large-scale applications, have addressed long-term public health risks using a holistic approach for assessing impacts from potential waterborne and airborne transport pathways. Multimedia models such as the Multimedia Environmental Pollutant Assessment System (MEPAS) were designed for use in such applications. MEPAS integrates radioactive and hazardous contaminants impact computations for major exposure routes via air, surface water, ground water, and overland flow transport. A number of large-scale applications of MEPAS have been conducted to assess various endpoints for environmental and human health impacts. These applications are described in terms of lessons learned in the development of an effective approach for large-scale applications

  19. Hot seeding using large Y-123 seeds

    International Nuclear Information System (INIS)

    Scruggs, S J; Putman, P T; Zhou, Y X; Fang, H; Salama, K

    2006-01-01

    There are several motivations for increasing the diameter of melt textured single domain discs. The maximum magnetic field produced by a trapped field magnet is proportional to the radius of the sample. Furthermore, the availability of trapped field magnets with large diameter could enable their use in applications that have traditionally been considered to require wound electromagnets, such as beam bending magnets for particle accelerators and electric propulsion. We have investigated the possibility of using large area epitaxial growth instead of the conventional point nucleation growth mechanism. This process involves the use of large Y123 seeds for the purpose of increasing the maximum achievable Y123 single domain size. The hot seeding technique using large Y-123 seeds was employed to seed Y-123 samples. Trapped field measurements indicate that single domain samples were indeed grown by this technique. Microstructural evaluation indicates that growth can be characterized by a rapid nucleation followed by the usual peritectic grain growth which occurs when large seeds are used. Critical temperature measurements show that no local T c suppression occurs in the vicinity of the seed. This work supports the suggestion of using an iterative method for increasing the size of Y-123 single domains that can be grown

  20. Abelian scalar theory at large global charge

    Energy Technology Data Exchange (ETDEWEB)

    Loukas, Orestis [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics, University of Bern (Switzerland)

    2017-09-15

    We elaborate on Abelian complex scalar models, which are dictated by natural actions (all couplings are of order one), at fixed and large global U(1) charge in an arbitrary number of dimensions. The ground state vertical stroke v right angle is coherently constructed by the zero modes and the appearance of a centrifugal potential is quantum mechanically verified. Using the path integral formulation we systematically analyze the quantum fluctuations around vertical stroke v right angle in order to derive an effective action for the Goldstone mode, which becomes perturbatively meaningful when the charge is large. In this regime we explicitly show, by computing the first few loop corrections, that the whole construction is stable against quantum effects, in the sense that any higher derivative couplings to Goldstone's tree-level action are suppressed by appropriate powers of the large charge. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Charging in the environment of large spacecraft

    International Nuclear Information System (INIS)

    Lai, S.T.

    1993-01-01

    This paper discusses some potential problems of spacecraft charging as a result of interactions between a large spacecraft, such as the Space Station, and its environment. Induced electric field, due to VXB effect, may be important for large spacecraft at low earth orbits. Differential charging, due to different properties of surface materials, may be significant when the spacecraft is partly in sunshine and partly in shadow. Triple-root potential jump condition may occur because of differential charging. Sudden onset of severe differential charging may occur when an electron or ion beam is emitted from the spacecraft. The beam may partially return to the ''hot spots'' on the spacecraft. Wake effects, due to blocking of ambient ion trajectories, may result in an undesirable negative potential region in the vicinity of a large spacecraft. Outgassing and exhaust may form a significant spacecraft induced environment; ionization may occur. Spacecraft charging and discharging may affect the electronic components on board

  2. Endoscopic treatment of large vesical calculi

    International Nuclear Information System (INIS)

    Rauf, A.; Ahmed, I.; Rauf, M.H.; Rauf, M.

    2015-01-01

    Objective: To determine the efficiency and safety of endoscopic treatment of large vesical calculi with the available modern endoscopic instruments. Methology: In case series, patients were collected randomly from 2007 to 2014. Patients were diagnosed with ultrasound and Nephroscope with Swiss pneumatic lithoclast, lithotrite and stone punch were used for treatment. Results: Majority of the patient could be managed with the method adopted. Stone size, hardness or softness, gender were the factors affecting treatment. Associated prostate pathology was seen in four patients. Postoperative complications included hemorrhage, perforation, residual stone and transurethral resection of prostate syndrome. Conclusion: Overall, it is a safe procedure except in patients with large enlarged prostate and large vesical calculi. Very hard vesical calculus may need vesicolithotomy. (author)

  3. Growth Limits in Large Scale Networks

    DEFF Research Database (Denmark)

    Knudsen, Thomas Phillip

    limitations. The rising complexity of network management with the convergence of communications platforms is shown as problematic for both automatic management feasibility and for manpower resource management. In the fourth step the scope is extended to include the present society with the DDN project as its......The Subject of large scale networks is approached from the perspective of the network planner. An analysis of the long term planning problems is presented with the main focus on the changing requirements for large scale networks and the potential problems in meeting these requirements. The problems...... the fundamental technological resources in network technologies are analysed for scalability. Here several technological limits to continued growth are presented. The third step involves a survey of major problems in managing large scale networks given the growth of user requirements and the technological...

  4. ISLA: An Isochronous Spectrometer with Large Acceptances

    Energy Technology Data Exchange (ETDEWEB)

    Bazin, D., E-mail: bazin@nscl.msu.edu; Mittig, W.

    2013-12-15

    A novel type of recoil mass spectrometer and separator is proposed for the future secondary radioactive beams of the ReA12 accelerator at NSCL/FRIB, inspired from the TOFI spectrometer developed at the Los Alamos National Laboratory for online mass measurements. The Isochronous Spectrometer with Large Acceptances (ISLA) is able to achieve superior characteristics without the compromises that usually plague the design of large acceptance spectrometers. ISLA can provide mass-to-charge ratio (m/q) measurements to better than 1 part in 1000 by using an optically isochronous time-of-flight independent of the momentum vector of the recoiling ions, despite large acceptances of 20% in momentum and 64 msr in solid angle. The characteristics of this unique design are shown, including requirements for auxiliary detectors around the target and the various types of reactions to be used with the re-accelerated radioactive beams of the future ReA12 accelerator.

  5. A large electrically excited synchronous generator

    DEFF Research Database (Denmark)

    2014-01-01

    This invention relates to a large electrically excited synchronous generator (100), comprising a stator (101), and a rotor or rotor coreback (102) comprising an excitation coil (103) generating a magnetic field during use, wherein the rotor or rotor coreback (102) further comprises a plurality...... adjacent neighbouring poles. In this way, a large electrically excited synchronous generator (EESG) is provided that readily enables a relatively large number of poles, compared to a traditional EESG, since the excitation coil in this design provides MMF for all the poles, whereas in a traditional EESG...... each pole needs its own excitation coil, which limits the number of poles as each coil will take up too much space between the poles....

  6. Trust dynamics in a large system implementation

    DEFF Research Database (Denmark)

    Schlichter, Bjarne Rerup; Rose, Jeremy

    2013-01-01

    outcomes, but largely ignored the dynamics of trust relations. Giddens, as part of his study of modernity, theorises trust dynamics in relation to abstract social systems, though without focusing on information systems. We use Giddens’ concepts to investigate evolving trust relationships in a longitudinal......A large information systems implementation (such as Enterprise Resource Planning systems) relies on the trust of its stakeholders to succeed. Such projects impact diverse groups of stakeholders, each with their legitimate interests and expectations. Levels of stakeholder trust can be expected...... case analysis of a large Integrated Hospital System implementation for the Faroe Islands. Trust relationships suffered a serious breakdown, but the project was able to recover and meet its goals. We develop six theoretical propositions theorising the relationship between trust and project outcomes...

  7. Emerging large-scale solar heating applications

    International Nuclear Information System (INIS)

    Wong, W.P.; McClung, J.L.

    2009-01-01

    Currently the market for solar heating applications in Canada is dominated by outdoor swimming pool heating, make-up air pre-heating and domestic water heating in homes, commercial and institutional buildings. All of these involve relatively small systems, except for a few air pre-heating systems on very large buildings. Together these applications make up well over 90% of the solar thermal collectors installed in Canada during 2007. These three applications, along with the recent re-emergence of large-scale concentrated solar thermal for generating electricity, also dominate the world markets. This paper examines some emerging markets for large scale solar heating applications, with a focus on the Canadian climate and market. (author)

  8. Constituent models and large transverse momentum reactions

    International Nuclear Information System (INIS)

    Brodsky, S.J.

    1975-01-01

    The discussion of constituent models and large transverse momentum reactions includes the structure of hard scattering models, dimensional counting rules for large transverse momentum reactions, dimensional counting and exclusive processes, the deuteron form factor, applications to inclusive reactions, predictions for meson and photon beams, the charge-cubed test for the e/sup +-/p → e/sup +-/γX asymmetry, the quasi-elastic peak in inclusive hadronic reactions, correlations, and the multiplicity bump at large transverse momentum. Also covered are the partition method for bound state calculations, proofs of dimensional counting, minimal neutralization and quark--quark scattering, the development of the constituent interchange model, and the A dependence of high transverse momentum reactions

  9. Policy and planning for large infrastructure projects

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent

    2005-01-01

    This paper focuses on problems and their causes and cures in policy and planning for large infrastructure projects. First, it identifies as the main problem in major infrastructure development pervasive misinformation about the costs, benefits, and risks involved. A consequence of misinformation ...... for large infrastructure projects, with a focus on better planning methods and changed governance structures, the latter being more important.......This paper focuses on problems and their causes and cures in policy and planning for large infrastructure projects. First, it identifies as the main problem in major infrastructure development pervasive misinformation about the costs, benefits, and risks involved. A consequence of misinformation...... the likelihood that it is their projects, and not the competition's, that gain approval and funding. This results in the "survival of the unfittest," where often it is not the best projects that are built, but the most misrepresented ones. Finally, the paper presents measures for reforming policy and planning...

  10. Phonetic search methods for large speech databases

    CERN Document Server

    Moyal, Ami; Tetariy, Ella; Gishri, Michal

    2013-01-01

    “Phonetic Search Methods for Large Databases” focuses on Keyword Spotting (KWS) within large speech databases. The brief will begin by outlining the challenges associated with Keyword Spotting within large speech databases using dynamic keyword vocabularies. It will then continue by highlighting the various market segments in need of KWS solutions, as well as, the specific requirements of each market segment. The work also includes a detailed description of the complexity of the task and the different methods that are used, including the advantages and disadvantages of each method and an in-depth comparison. The main focus will be on the Phonetic Search method and its efficient implementation. This will include a literature review of the various methods used for the efficient implementation of Phonetic Search Keyword Spotting, with an emphasis on the authors’ own research which entails a comparative analysis of the Phonetic Search method which includes algorithmic details. This brief is useful for resea...

  11. Managing large-scale models: DBS

    International Nuclear Information System (INIS)

    1981-05-01

    A set of fundamental management tools for developing and operating a large scale model and data base system is presented. Based on experience in operating and developing a large scale computerized system, the only reasonable way to gain strong management control of such a system is to implement appropriate controls and procedures. Chapter I discusses the purpose of the book. Chapter II classifies a broad range of generic management problems into three groups: documentation, operations, and maintenance. First, system problems are identified then solutions for gaining management control are disucssed. Chapters III, IV, and V present practical methods for dealing with these problems. These methods were developed for managing SEAS but have general application for large scale models and data bases

  12. Accelerating sustainability in large-scale facilities

    CERN Multimedia

    Marina Giampietro

    2011-01-01

    Scientific research centres and large-scale facilities are intrinsically energy intensive, but how can big science improve its energy management and eventually contribute to the environmental cause with new cleantech? CERN’s commitment to providing tangible answers to these questions was sealed in the first workshop on energy management for large scale scientific infrastructures held in Lund, Sweden, on the 13-14 October.   Participants at the energy management for large scale scientific infrastructures workshop. The workshop, co-organised with the European Spallation Source (ESS) and  the European Association of National Research Facilities (ERF), tackled a recognised need for addressing energy issues in relation with science and technology policies. It brought together more than 150 representatives of Research Infrastrutures (RIs) and energy experts from Europe and North America. “Without compromising our scientific projects, we can ...

  13. Noise Pulses in Large Area Optical Modules

    International Nuclear Information System (INIS)

    Aiello, Sebastiano; Leonora, Emanuele; Giordano, Valentina

    2013-06-01

    A great number of large area photomultipliers are widely used in neutrino and astro-particle detector to measure Cherenkov light in medium like water or ice. The key element of these detectors are the so-called 'optical module', which consist in photodetectors closed in a transparent pressure-resistant container to protect it and ensure good light transmission. The noise pulses present on the anode of each photomultiplier affect strongly the performance of the detector. A large study was conducted on noise pulses of large area photomultipliers, considering time and charge distributions of dark pulses, prepulses, delayed pulses, and after pulses. The contribution to noise pulses due to the presence of the external glass spheres was also studied, even comparing two vessels of different brands. (authors)

  14. Transport Coefficients from Large Deviation Functions

    Directory of Open Access Journals (Sweden)

    Chloe Ya Gao

    2017-10-01

    Full Text Available We describe a method for computing transport coefficients from the direct evaluation of large deviation functions. This method is general, relying on only equilibrium fluctuations, and is statistically efficient, employing trajectory based importance sampling. Equilibrium fluctuations of molecular currents are characterized by their large deviation functions, which are scaled cumulant generating functions analogous to the free energies. A diffusion Monte Carlo algorithm is used to evaluate the large deviation functions, from which arbitrary transport coefficients are derivable. We find significant statistical improvement over traditional Green–Kubo based calculations. The systematic and statistical errors of this method are analyzed in the context of specific transport coefficient calculations, including the shear viscosity, interfacial friction coefficient, and thermal conductivity.

  15. Transport Coefficients from Large Deviation Functions

    Science.gov (United States)

    Gao, Chloe; Limmer, David

    2017-10-01

    We describe a method for computing transport coefficients from the direct evaluation of large deviation function. This method is general, relying on only equilibrium fluctuations, and is statistically efficient, employing trajectory based importance sampling. Equilibrium fluctuations of molecular currents are characterized by their large deviation functions, which is a scaled cumulant generating function analogous to the free energy. A diffusion Monte Carlo algorithm is used to evaluate the large deviation functions, from which arbitrary transport coefficients are derivable. We find significant statistical improvement over traditional Green-Kubo based calculations. The systematic and statistical errors of this method are analyzed in the context of specific transport coefficient calculations, including the shear viscosity, interfacial friction coefficient, and thermal conductivity.

  16. Emerging large-scale solar heating applications

    Energy Technology Data Exchange (ETDEWEB)

    Wong, W.P.; McClung, J.L. [Science Applications International Corporation (SAIC Canada), Ottawa, Ontario (Canada)

    2009-07-01

    Currently the market for solar heating applications in Canada is dominated by outdoor swimming pool heating, make-up air pre-heating and domestic water heating in homes, commercial and institutional buildings. All of these involve relatively small systems, except for a few air pre-heating systems on very large buildings. Together these applications make up well over 90% of the solar thermal collectors installed in Canada during 2007. These three applications, along with the recent re-emergence of large-scale concentrated solar thermal for generating electricity, also dominate the world markets. This paper examines some emerging markets for large scale solar heating applications, with a focus on the Canadian climate and market. (author)

  17. Anomalies and the Large N Limit

    International Nuclear Information System (INIS)

    Agarwal, A.; Akant, L.

    2003-01-01

    Operator algebra aspects of the Large N limit of Bosonic vector models are analyzed. It is shown that the Large N limit is a classical theory, and a general method, based on defromation quatization, for calculating the Poisson algebra of dynamical observables in the limiting classical theory is presented. The Poisson algebra of O(N) invariant observables of Bosonic vector models is constructed in this approach, and is shown to be a central extension of the Symplectic Lie algebra. The relation of the central term to anomalies is discussed. A comparision of the classical theories obtained in the Large N limit and that in the small (ℎ/2π) limit is also presented

  18. Risk Management of Large Component in Decommissioning

    Energy Technology Data Exchange (ETDEWEB)

    Nah, Kyung Ku; Kim, Tae Ryong [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2014-10-15

    The need for energy, especially electric energy, has been dramatically increasing in Korea. Therefore, a rapid growth in nuclear power development has been achieved to have about 30% of electric power production. However, such a large nuclear power generation has been producing a significant amount of radioactive waste and other matters such as safety issue. In addition, owing to the severe accidents at the Fukushima in Japan, public concerns regarding NPP and radiation hazard have greatly increased. In Korea, the operation of KORI 1 has been scheduled to be faced with end of lifetime in several years and Wolsong 1 has been being under review for extending its life. This is the reason why the preparation of nuclear power plant decommissioning is significant in this time. Decommissioning is the final phase in the life-cycle of a nuclear facility and during decommissioning operation, one of the most important management in decommissioning is how to deal with the disused large component. Therefore, in this study, the risk in large component in decommissioning is to be identified and the key risk factor is to be analyzed from where can be prepared to handle decommissioning process safely and efficiently. Developing dedicated acceptance criteria for large components at disposal site was analyzed as a key factor. Acceptance criteria applied to deal with large components like what size of those should be and how to be taken care of during disposal process strongly affect other major works. For example, if the size of large component was not set up at disposal site, any dismantle work in decommissioning is not able to be conducted. Therefore, considering insufficient time left for decommissioning of some NPP, it is absolutely imperative that those criteria should be laid down.

  19. Risk Management of Large Component in Decommissioning

    International Nuclear Information System (INIS)

    Nah, Kyung Ku; Kim, Tae Ryong

    2014-01-01

    The need for energy, especially electric energy, has been dramatically increasing in Korea. Therefore, a rapid growth in nuclear power development has been achieved to have about 30% of electric power production. However, such a large nuclear power generation has been producing a significant amount of radioactive waste and other matters such as safety issue. In addition, owing to the severe accidents at the Fukushima in Japan, public concerns regarding NPP and radiation hazard have greatly increased. In Korea, the operation of KORI 1 has been scheduled to be faced with end of lifetime in several years and Wolsong 1 has been being under review for extending its life. This is the reason why the preparation of nuclear power plant decommissioning is significant in this time. Decommissioning is the final phase in the life-cycle of a nuclear facility and during decommissioning operation, one of the most important management in decommissioning is how to deal with the disused large component. Therefore, in this study, the risk in large component in decommissioning is to be identified and the key risk factor is to be analyzed from where can be prepared to handle decommissioning process safely and efficiently. Developing dedicated acceptance criteria for large components at disposal site was analyzed as a key factor. Acceptance criteria applied to deal with large components like what size of those should be and how to be taken care of during disposal process strongly affect other major works. For example, if the size of large component was not set up at disposal site, any dismantle work in decommissioning is not able to be conducted. Therefore, considering insufficient time left for decommissioning of some NPP, it is absolutely imperative that those criteria should be laid down

  20. Managing conflict between large carnivores and livestock.

    Science.gov (United States)

    van Eeden, Lily M; Crowther, Mathew S; Dickman, Chris R; Macdonald, David W; Ripple, William J; Ritchie, Euan G; Newsome, Thomas M

    2018-02-01

    Large carnivores are persecuted globally because they threaten human industries and livelihoods. How this conflict is managed has consequences for the conservation of large carnivores and biodiversity more broadly. Mitigating human-predator conflict should be evidence-based and accommodate people's values while protecting carnivores. Despite much research into human and large-carnivore coexistence strategies, there have been few attempts to document the success of conflict-mitigation strategies on a global scale. We conducted a meta-analysis of global research on conflict mitigation related to large carnivores and humans. We focused on conflicts that arise from the threat large carnivores pose to livestock. We first used structured and unstructured searching to identify replicated studies that used before-after or control-impact design to measure change in livestock loss as a result of implementing a management intervention. We then extracted relevant data from these studies to calculate an overall effect size for each intervention type. Research effort and focus varied among continents and aligned with the histories and cultures that shaped livestock production and attitudes toward carnivores. Livestock guardian animals most effectively reduced livestock losses. Lethal control was the second most effective control, although its success varied the most, and guardian animals and lethal control did not differ significantly. Financial incentives have promoted tolerance of large carnivores in some settings and reduced retaliatory killings. We suggest coexistence strategies be location-specific, incorporate cultural values and environmental conditions, and be designed such that return on financial investment can be evaluated. Improved monitoring of mitigation measures is urgently required to promote effective evidence-based policy. © 2017 Society for Conservation Biology.