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Sample records for avastin gbm briefing

  1. Avastin exhibits therapeutic effects on collagen-induced arthritis in rat model.

    Science.gov (United States)

    Wang, Yong; Da, Gula; Li, Hongbin; Zheng, Yi

    2013-12-01

    Avastin is the monoclonal antibody for vascular endothelial growth factor (VEGF). This study aimed to investigate therapeutic effect of Avastin on type II collagen-induced arthritis. Type II chicken collagen was injected into the tails of Wistar rats, and 60 modeled female rats were randomly divided into three groups (n = 20): Avastin group, Etanercept group, and control group. Arthritis index and joint pad thickness were scored, and the pathology of back metapedes was analyzed. The results showed that compared to control group, the arthritis index, target-to-non-target ratio, synovial pathological injury index, serum levels of VEGF and tumor necrosis factor alpha, and VEGF staining were decreased significantly 14 days after Avastin or Etanercept treatment, but there were no significant differences between Avastin group and Etanercept group. These data provide evidence that Avastin exhibits similar effects to Etanercept to relieve rheumatoid arthritis in rat model and suggest that Avastin is a promising therapeutic agent for rheumatoid arthritis.

  2. Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma.

    Science.gov (United States)

    Barone, Amy; Sengupta, Rajarshi; Warrington, Nicole M; Smith, Erin; Wen, Patrick Y; Brekken, Rolf A; Romagnoli, Barbara; Douglas, Garry; Chevalier, Eric; Bauer, Michael P; Dembowsky, Klaus; Piwnica-Worms, David; Rubin, Joshua B

    2014-10-30

    Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM.

  3. Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

    Science.gov (United States)

    Jansen, Rita-Marié; Gouws, Chris

    2009-06-01

    Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use

  4. Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of gestation and the impact of neonatal Fc receptor (FcRn) binding.

    Science.gov (United States)

    Thorn, Mitchell; Piche-Nicholas, Nicole; Stedman, Donald; Davenport, Scott W; Zhang, Ning; Collinge, Mark; Bowman, Christopher J

    2012-10-01

    There is concern about embryo-fetal exposure to antibody-based biopharmaceuticals based on the increase of such therapies being prescribed to women of childbearing potential. Therefore, there is a desire to better characterize embryo-fetal exposure of these molecules. The pregnant rat is a standard model for evaluating the potential consequences of exposure but placental transfer of antibody-based biopharmaceuticals is not well understood in this model. The relative embryo-fetal distribution of an antibody-based biopharmaceutical was evaluated in the rat. Bevacizumab (Avastin) was chosen as a tool antibody since it does not have significant target binding in the rat that might influence embryo-fetal biodistribution. Avastin was labeled with a fluorescent dye, characterized, and injected into pregnant rats at different gestation ages. Labeled Avastin in fetal tissues was visualized ex vivo using an IVIS 200 (Caliper, A PerkinElmer Company, Alameda, CA). Avastin localized to the fetus as early as 24-hr post intravenous injection of the dam, and was taken up by the fetus in a dose-dependent manner. Avastin was detectable in the developing embryo as early as gestation day 13 and continued to be transferred until the end of gestation. Fetal transfer of Avastins mutated in the portion of the antibody that binds the neonatal Fc receptor (FcRn) was tested in late gestation and was found to correlate with affinities of the mutant Avastin antibody to FcRn. The novel application of this imaging technology was used to characterize the onset and duration of Avastin maternal-fetal transfer in rats and the importance of FcRn binding. © 2012 Wiley Periodicals, Inc.

  5. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

    Directory of Open Access Journals (Sweden)

    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

  6. Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.

    Science.gov (United States)

    Binder, Zev A; Wilson, Kelli M; Salmasi, Vafi; Orr, Brent A; Eberhart, Charles G; Siu, I-Mei; Lim, Michael; Weingart, Jon D; Quinones-Hinojosa, Alfredo; Bettegowda, Chetan; Kassam, Amin B; Olivi, Alessandro; Brem, Henry; Riggins, Gregory J; Gallia, Gary L

    2016-01-01

    Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

  7. The Accuracy of GBM GRB Localizations

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    Briggs, Michael Stephen; Connaughton, V.; Meegan, C.; Hurley, K.

    2010-03-01

    We report an study of the accuracy of GBM GRB localizations, analyzing three types of localizations: those produced automatically by the GBM Flight Software on board GBM, those produced automatically with ground software in near real time, and localizations produced with human guidance. The two types of automatic locations are distributed in near real-time via GCN Notices; the human-guided locations are distributed on timescale of many minutes or hours using GCN Circulars. This work uses a Bayesian analysis that models the distribution of the GBM total location error by comparing GBM locations to more accurate locations obtained with other instruments. Reference locations are obtained from Swift, Super-AGILE, the LAT, and with the IPN. We model the GBM total location errors as having systematic errors in addition to the statistical errors and use the Bayesian analysis to constrain the systematic errors.

  8. Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita; Wang, Nicholas J.; Smirnov, Ivan; Yu, Mamie; Hariono, Sujatmi; Silber, Joachim; Feiler, Heidi S.; Gray, Joe W.; Spellman, Paul T.; Vandenberg, Scott R.; Berger, Mitchel S.; James, C. David

    2009-04-03

    Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.

  9. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled...... was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow-up examinations (P Macular thickness improved significantly at all time...

  10. 77 FR 11554 - Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following...

    Science.gov (United States)

    2012-02-27

    ... who have not received chemotherapy for treatment of HER2-negative metastatic breast cancer (MBC). This... requirement that the product be studied further to verify and describe its clinical benefit. On November 16... determined that these trials failed to verify AVASTIN's clinical benefit in the treatment of MBC and on...

  11. Opposing roles of PGD2 in GBM.

    Science.gov (United States)

    Ferreira, Matthew Thomas; Gomes, Renata Nascimento; Panagopoulos, Alexandros Theodoros; de Almeida, Fernando Gonçalves; Veiga, José Carlos Esteves; Colquhoun, Alison

    2018-01-01

    The World Health Organization classifies glioblastoma (GBM) as a grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patient's length of survival, the overall trajectory of the disease remains unchanged. GBM cells produce significant levels of various types of bioactive lipids. Prostaglandin D 2 (PGD 2 ) influences both pro- and anti-tumorigenic activities in the cell; however, its role in GBM is unclear. Therefore, this study aimed to identify the impact of PGD 2 on GBM cell activities in vitro. First we looked to identify the presence of the PGD 2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD 2 's effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (1μM) concentrations of PGD 2 over 72h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. We identified the presence of endogenous PGD 2 with its corresponding enzymes and receptors. Exogenous PGD 2 both increased cell count (GBM. Our study demonstrates that prostaglandin D 2 possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD 2 production in GBM patients suggests a pro-tumorigenic role of PGD 2 in glioma growth and invasion. Therefore, prostaglandin signaling in GBM requires further investigation to identify new targets for more effective therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

    2013-02-01

    Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

  13. Fermi GBM: Results from the First Year +

    Science.gov (United States)

    Wilson-Hodge, Colleen A.

    2009-01-01

    Gamma-ray Burst Monitor (GBM) has performed well in the first year+. GBM triggers 353 Gamma-ray Bursts (GRBs), 168 SGR events, 18 TGFs, and 1 solar flare to date. Short GRBs appear contracted in time and shifted to higher energy than long GRBs. Pulsed persistent emission from SGR 1550-5418 detected. TGFs are shorter, have higher average photon energies, and much higher count rates than GRBs. GBM monitoring of accreting pulsars provides long-term spin-histories. GBM Earth occultation monitoring complements Swift.

  14. A Proposal to Localize Fermi GBM GRBs Through Coordinated Scanning of the GBM Error Circle via Optical Telescopes

    Science.gov (United States)

    Ukwatta, T. N.; Linnemann, J. T.; Tollefson, K.; Abeysekara, A. U.; Bhat, P. N.; Sonbas, E.; Gehrels, N.

    2011-01-01

    We investigate the feasibility of implementing a system that will coordinate ground-based optical telescopes to cover the Fermi GBM Error Circle (EC). The aim of the system is to localize GBM detected GRBs and facilitate multi-wavelength follow-up from space and ground. This system will optimize the observing locations in the GBM EC based on individual telescope location, Field of View (FoV) and sensitivity. The proposed system will coordinate GBM EC scanning by professional as well as amateur astronomers around the world. The results of a Monte Carlo simulation to investigate the feasibility of the project are presented.

  15. Diagnosis and classification of Goodpasture's disease (anti-GBM).

    Science.gov (United States)

    Hellmark, Thomas; Segelmark, Mårten

    2014-01-01

    Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Role of avastin on the incidence of post-operative vitreous hemorrhage after vitrectomy in diabetic vitreous hemorrhage

    International Nuclear Information System (INIS)

    Ahmed, N.; Shaheer, M.; Tahir, M.Y.

    2014-01-01

    Diabetic retinopathy is one of the most common cause of legal blindness. Five to 10% of diabetic patients suffer from the proliferative diabetic retinopathy which includes the formation of new vessels on the retina and optic disc which can be complicated as vitreous hemorrhage and tractional retinal detachment. Pars plana vitrectomy along with laser photocoagulation is being used for the management of vitreous hemorrhage. In our study we used injection avastin one week before surgery to see its role on the incidence of rebleed after vitrectomy in diabetic vitreous hemorrhage. Materials and Methods; Fifty patients were divided into 2 equal groups on the basis of simple random sampling. 25 patients in Group I were operated with routine pars plana vitrectomy with endolaser photo- coagulation while in Group II all the 25 patients were given injection avastin intra-vitreally one week before surgery. Evaluation was done on the first post operative day, first follow up visit (one week) and after one month to see the incidence of re-bleed. Chi-square test was used for statistical analysis. Results: Fifty patients divided into two groups. In Group I, 3 patients had recurrent vitreous hemorrhage on first post-operative day, 3 patients had re-bleed on first follow up visit, and only 2 patients had re-bleed after one month. In Group II, none of the patients had recurrent vitreous hemorrhage on first post-operative day and on first follow-up visit (one week) while 2 patients had re-bleed after one month. Conclusion: Injection intravitreal Avastin (Bevaci- zumab) one week before surgery significantly reduces the risk of vitreous hemorrhage after vitrectomy in diabetic patients. (author)

  17. Magnetar Observations with Fermi/GBM

    Science.gov (United States)

    Kouveliotou, Chryssa

    2009-01-01

    NASA's Fermi Observatory was launched June 11, 2009; the Fermi Gamma Ray Burst Monitor (GBM) began normal operations on July 14, about a month after launch, when the trigger algorithms were enabled. In the first year of operations we recorded emission from four magnetar sources; of these, only one was an old magnetar: SGR 1806+20. The other three detections were: SGR J0501+4516, newly discovered with Swift and extensively monitored with both Swift and GBM, SGR J1550-5418, a source originally classified as an Anomalous X-ray Pulsar (AXP) and a very recently discovered new source, SGR 0418+5729. I report below on the current status of the analyses efforts of the GBM data.

  18. Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma; Interet d'un traitement combine par radioimmunotherapie et Avastin1 dans un modele murin de carcinome medullaire de la thyroide

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    Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F. [Unite Inserm U892, Brest, (France)

    2009-05-15

    The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

  19. Time-Domain Astronomy with the Fermi GBM

    Science.gov (United States)

    Hui, C. M.

    2017-01-01

    The Fermi Gamma-ray Burst Monitor (GBM) is an all-sky monitoring instrument sensitive to energies from 8 keV to 40 MeV. Over the past 8 years of operation, the GBM has detected over 240 gamma-ray bursts per year and provided timely GCN notices with localization to few-degree accuracy for follow-up observations. In addition to GRBs, Galactic transients, solar flares, and terrestrial gamma-ray flashes have also been observed. In recent years we have also been searching the continuous GBM data for electromagnetic counterpart to astrophysical neutrinos and gravitational wave events, as these are believed to be associated with gamma-ray bursts. With continuous data downlink every few hours and a temporal resolution of 2 microseconds, GBM is well suited for observing transients and supporting EM follow-up in the era of multi-messenger astronomy.

  20. Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma

    International Nuclear Information System (INIS)

    Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F.

    2009-01-01

    The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

  1. GBM Observations of Terrestrial Gamma-Ray Flashes

    Science.gov (United States)

    Briggs, M. S.; Fishman, G. J.; Connaughton, V.; Bhat, P. N.; Paciesas, W. S.; Preece, R. D.; Wilson-Hodge, C.; Chaplin, V. L.; Kippen, R. M.; vonKienlin, A.; hide

    2010-01-01

    The TGF detection rate of Gamma-ray Burst Monitor (GBM) has been increased twice since launch. The most recent improvement is from a new operating mode in which data for individual photons are down-linked for selected portions of the orbit, enabling a more sensitive ground-based search for TGFs. The new search has increased the TGF detection rate and is finding TGFs more than five times fainter than the TGFs of the previous GBM sample. We summarize the properties of the original GBM TGF sample and compare to the less intense TGFs now being detected. In addition to gamma-ray TGFs, GBM is observing distant TGFs from the propagation of charged particles along geomagnetic field lines. Strong 511 keV annihilation lines have been observed, demonstrating that both electrons and positrons are present in the particle beams. Spectral fits to these electron/positron TGFs will be shown.

  2. Three years of Transients with Fermi GBM

    Science.gov (United States)

    Wilson-Hodge, Colleen A.

    2012-01-01

    The Gamma-ray Burst Monitor (GBM) is an all-sky monitoring instrument, sensitive between 8 keV and 40 MeV, with a primary objective of supporting the Large Area Telescope (LAT) in observations of Gamma-Ray Bursts (GRBs). Both instruments are part of the Fermi Gamma-ray Space Telescope. Together, the GBM and LAT instruments have provided ground-breaking measurements of GRBs that have, after 10 years of focus on GRB afterglows, inspired renewed interest in the prompt emission phase of GRBs and the physical mechanisms that fuel them. In addition to GRB science, GBM has made significant contributions to the astrophysics of galactic transient sources including long-term variations in the Crab nebula, spin state transitions in accretion powered pulsars, state transitions in black hole X-ray binaries, and unprecedented time-resolved spectral studies of soft gamma-ray repeater bursts. Closer to home, GBM also contributes to solar flare and terrestrial gamma flash science.

  3. Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells.

    Science.gov (United States)

    Mukherjee, Sumit; Baidoo, Juliet N E; Sampat, Samay; Mancuso, Andrew; David, Lovena; Cohen, Leah S; Zhou, Shuiqin; Banerjee, Probal

    2018-01-18

    Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

  4. Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM and GBM Stem Cells

    Directory of Open Access Journals (Sweden)

    Sumit Mukherjee

    2018-01-01

    Full Text Available Glioblastoma (GBM is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E from green tea and resveratrol (R from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM: 32:8:100 (termed 32 μM+ TriCurin. We have now prepared liposomal TriCurin (TrLp and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

  5. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes by...... these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection....

  6. The Fermi-GBM Gamma-Ray Burst Catalogs: The First Six Years

    Directory of Open Access Journals (Sweden)

    Bissaldi E.

    2017-01-01

    Full Text Available Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM has triggered and located on average approximately two gamma-ray bursts (GRBs every three days. Here we present the main results from the latest two catalogs provided by the Fermi-GBM science team, namely the third GBM GRB catalog [1] and the first GBM time-resolved spectral catalog [2]. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected bursts. It comprises 1405 triggers identified as GRBs. For each one, location and main characteristics of the prompt emission, the duration, the peak flux and the fluence are derived. The GBM time-resolved spectral catalog presents high-quality time-resolved spectral analysis with high temporal and spectral resolution of the brightest bursts observed by Fermi GBM in a shorter period than the former catalog, namely four years. It comprises 1491 spectra from 81 bursts. Distributions of parameters, statistics of the parameter populations, parameter-parameter and parameter-uncertainty correlations, and their exact values are obtained.

  7. Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics.

    Science.gov (United States)

    Appin, Christina L; Gao, Jingjing; Chisolm, Candace; Torian, Mike; Alexis, Dianne; Vincentelli, Cristina; Schniederjan, Matthew J; Hadjipanayis, Costas; Olson, Jeffrey J; Hunter, Stephen; Hao, Chunhai; Brat, Daniel J

    2013-07-01

    Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics. © 2013 The Authors; Brain Pathology © 2013 International Society of Neuropathology.

  8. The Fermi GBM catalog (Paciesas+, 2012) [Dataset

    NARCIS (Netherlands)

    Paciesas, W.S.; Meegan, C.A.; von Kienlin, A.; Bhat, P.N.; Bissaldi, E.; Briggs, M.S.; Burgess, J.M.; Chaplin, V.; Connaughton, V.; Diehl, R.; Fishman, G.J.; Fitzpatrick, G.; Foley, S.; H. Gibby, M.; Giles, M.; Goldstein, A.; Greiner, J.; Gruber, D.; Guiriec, S.; van der Horst, A.J.; Kippen, R.M.; Kouveliotou, C.; Lichti, G.; Lin, L.; McBreen, S.; Preece, R.D.; Rau, A.; Tierney, D.; Wilson-Hodge, C.

    2012-01-01

    The Fermi Gamma-ray Space Telescope was launched on 2008 June 11 on a mission to study the universe at high energies. The onboard Gamma-ray Burst Monitor (GBM) trigger system for detecting GRBs was first enabled on 2008 July 12. In this paper, we provide a catalog of GRBs that triggered the GBM

  9. High-energy transients with Fermi/GBM

    International Nuclear Information System (INIS)

    Gruber, David

    2012-01-01

    For most of mankind's history, astronomy was performed on-ground in the optical energy range. It was only when space-based missions, built more than 50 years ago, detected photons with mind-boggling energies that the exploration of the violent Universe really began. These γ-ray photons still provide us with an unprecedented wealth of information for the most energetic processes taking place in the cosmos. Faithful to the olympic slogan ''higher, faster, further'', an increasing armada of γ-ray satellites was built and launched over the last couple of decades with Fermi being the youngest of its kind. In this thesis, I use data from the Gamma-Ray Burst Monitor (GBM) onboard the Fermi satellite. The focus of this work lies on three very different classes of high-energy astrophysical transients: Gamma-Ray Bursts (GRBs), solar flares and Soft Gamma Repeaters (SGRs). In Chapter 2, I present GRB 091024A, a burst of very long duration in γ-rays where optical data could be acquired well during its active phase. The optical light curve shows very intriguing features which I subsequently interpret as the so called ''optical flash'', a fundamental property of the ''fireball'' model. Although predicted by the latter model, only a handful of GRBs show such a behavior, making them interesting transients to study. Furthermore, I present the fundamental temporal and spectral properties of 47 GBM-detected GRBs with known redshifts. As GRBs explode at cosmological distances it is of uttermost importance to study them in their restframe to get a better understanding of their emission mechanisms. I confirm several correlations already found in the past together with an intriguing connection between redshift and the peak energy (E peak ) of GRBs. Although this correlation is heavily influenced by instrumental effects, it is not unexpected from other experimental results, giving it more credibility. Finally, I present the results of the search for untriggered GRBs in GBM data. This

  10. High-energy transients with Fermi/GBM

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, David

    2012-10-09

    For most of mankind's history, astronomy was performed on-ground in the optical energy range. It was only when space-based missions, built more than 50 years ago, detected photons with mind-boggling energies that the exploration of the violent Universe really began. These {gamma}-ray photons still provide us with an unprecedented wealth of information for the most energetic processes taking place in the cosmos. Faithful to the olympic slogan ''higher, faster, further'', an increasing armada of {gamma}-ray satellites was built and launched over the last couple of decades with Fermi being the youngest of its kind. In this thesis, I use data from the Gamma-Ray Burst Monitor (GBM) onboard the Fermi satellite. The focus of this work lies on three very different classes of high-energy astrophysical transients: Gamma-Ray Bursts (GRBs), solar flares and Soft Gamma Repeaters (SGRs). In Chapter 2, I present GRB 091024A, a burst of very long duration in {gamma}-rays where optical data could be acquired well during its active phase. The optical light curve shows very intriguing features which I subsequently interpret as the so called ''optical flash'', a fundamental property of the ''fireball'' model. Although predicted by the latter model, only a handful of GRBs show such a behavior, making them interesting transients to study. Furthermore, I present the fundamental temporal and spectral properties of 47 GBM-detected GRBs with known redshifts. As GRBs explode at cosmological distances it is of uttermost importance to study them in their restframe to get a better understanding of their emission mechanisms. I confirm several correlations already found in the past together with an intriguing connection between redshift and the peak energy (E{sub peak}) of GRBs. Although this correlation is heavily influenced by instrumental effects, it is not unexpected from other experimental results, giving it more credibility

  11. Intravitreal bevacizumab (Avastin for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Shah Parag

    2007-01-01

    Full Text Available Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type II/rush disease occurs in zone 1 or posterior zone 2. Treatment involves extensive near confluent laser ablation of a large area of avascular retina. Anterior segment ischemia is a rare complication that can occur due to injury to the long posterior ciliary arteries in the horizontal meridians during aggressive posterior laser treatment. The outcome of this rare complication is very poor. This case describes a favorable outcome of intravitreal injection of bevacizumab (Avastin in a case of anterior segment ischemia.

  12. Magnetar Observations in the Swift-Fermi/GBM Era

    Science.gov (United States)

    Kouveliotou, Chryssa

    2010-01-01

    NASA's Fermi Observatory was launched June 11, 2008; the Fermi Gamma Ray Burst Monitor (GBM) began normal operations on July 14, about a month after launch, when the trigger algorithms were enabled. Since then, and against all odds, GBM recorded over 600 bursts from 4 SGRs. Of these four sources, only one was an old magnetar: SGR J1806+20. SGR J0501+4516, was discovered with Swift and extensively monitored with GBM. A source originally classified as AXP 1E1547.0-5408 exhibited SGR-like bursting behavior and we reclassified it as SGR J1550-5418. Finally, GBM discovered SGR J0418+5729 on 2009 June. Finally, on March 2010, a third new magnetar was discovered with Swift, SGR J1833-0832. I report below on the current status of the field and on several results combining multi-satellite and ground-based data

  13. The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

    Science.gov (United States)

    Teo, Mario; Clark, Brian; MacKinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

    2014-06-01

    It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

  14. Fermi/GBM Results of Magnetars

    Science.gov (United States)

    Kouveliotou, chryssa

    2011-01-01

    Magnetars are magnetically powered rotating neutron stars with extreme magnetic fields (over 10(exp 14) Gauss). They were discovered in the X- and gamma-rays where they predominantly emit their radiation. Very few sources (roughly 18) have been found since their discovery in 1987. NASA's Fermi Gamma-ray Space Telescope was launched June 11,2009; since then the Fermi Gamma-ray Burst Monitor (GBM) recorded emission from four magnetar sources. Two of these were brand new sources, SGR J0501 +4516, discovered with Swift and extensively monitored with Swift and GBM, SGR J0418+5729, discovered with GBM and the Interplanetary Network (IPN). A third was SGR Jl550-5418, a source originally classified as an Anomalous X-ray Pulsar (AXP IEI547.0-5408), but exhibiting a very prolific outburst with over 400 events recorded in January 2009. In my talk I will give a short history of magnetars and describe how this, once relatively esoteric field, has emerged as a link between several astrophysical areas including Gamma-Ray Bursts. Finally, I will describe the exciting new results of Fermi in this field and the current status of our knowledge of the magnetar population properties and magnetic fields.

  15. Surprisal analysis of Glioblastoma Multiform (GBM) microRNA dynamics unveils tumor specific phenotype.

    Science.gov (United States)

    Zadran, Sohila; Remacle, Francoise; Levine, Raphael

    2014-01-01

    Gliomablastoma multiform (GBM) is the most fatal form of all brain cancers in humans. Currently there are limited diagnostic tools for GBM detection. Here, we applied surprisal analysis, a theory grounded in thermodynamics, to unveil how biomolecule energetics, specifically a redistribution of free energy amongst microRNAs (miRNAs), results in a system deviating from a non-cancer state to the GBM cancer -specific phenotypic state. Utilizing global miRNA microarray expression data of normal and GBM patients tumors, surprisal analysis characterizes a miRNA system response capable of distinguishing GBM samples from normal tissue biopsy samples. We indicate that the miRNAs contributing to this system behavior is a disease phenotypic state specific to GBM and is therefore a unique GBM-specific thermodynamic signature. MiRNAs implicated in the regulation of stochastic signaling processes crucial in the hallmarks of human cancer, dominate this GBM-cancer phenotypic state. With this theory, we were able to distinguish with high fidelity GBM patients solely by monitoring the dynamics of miRNAs present in patients' biopsy samples. We anticipate that the GBM-specific thermodynamic signature will provide a critical translational tool in better characterizing cancer types and in the development of future therapeutics for GBM.

  16. Anti-GBM disease and ANCA during dengue infection.

    Science.gov (United States)

    Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

    2015-02-01

    Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

  17. GBM secretome induces transient transformation of human neural precursor cells.

    Science.gov (United States)

    Venugopal, Chitra; Wang, X Simon; Manoranjan, Branavan; McFarlane, Nicole; Nolte, Sara; Li, Meredith; Murty, Naresh; Siu, K W Michael; Singh, Sheila K

    2012-09-01

    Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, with a uniformly poor prognosis. The tumor microenvironment is composed of both supportive cellular substrates and exogenous factors. We hypothesize that exogenous factors secreted by brain tumor initiating cells (BTICs) could predispose normal neural precursor cells (NPCs) to transformation. When NPCs are grown in GBM-conditioned media, and designated as "tumor-conditioned NPCs" (tcNPCs), they become highly proliferative and exhibit increased stem cell self-renewal, or the unique ability of stem cells to asymmetrically generate another stem cell and a daughter cell. tcNPCs also show an increased transcript level of stem cell markers such as CD133 and ALDH and growth factor receptors such as VEGFR1, VEGFR2, EGFR and PDGFRα. Media analysis by ELISA of GBM-conditioned media reveals an elevated secretion of growth factors such as EGF, VEGF and PDGF-AA when compared to normal neural stem cell-conditioned media. We also demonstrate that tcNPCs require prolonged or continuous exposure to the GBM secretome in vitro to retain GBM BTIC characteristics. Our in vivo studies reveal that tcNPCs are unable to form tumors, confirming that irreversible transformation events may require sustained or prolonged presence of the GBM secretome. Analysis of GBM-conditioned media by mass spectrometry reveals the presence of secreted proteins Chitinase-3-like 1 (CHI3L1) and H2A histone family member H2AX. Collectively, our data suggest that GBM-secreted factors are capable of transiently altering normal NPCs, although for retention of the transformed phenotype, sustained or prolonged secretome exposure or additional transformation events are likely necessary.

  18. Podocyte Depletion in Thin GBM and Alport Syndrome.

    Science.gov (United States)

    Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

    2016-01-01

    The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at 70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

  19. Apparent diffusion coefficient in glioblastoma with PNET-like components, a GBM variant.

    Science.gov (United States)

    Ali, Saad; Joseph, Nancy M; Perry, Arie; Barajas, Ramon F; Cha, Soonmee

    2014-09-01

    Glioblastoma (GBM) with primitive neuroectodermal tumor (PNET)-like (GBM-PNET) components is a rare variant of GBM. Recent studies describe PNET-like clinical behavior in these patients-with significantly increased propensity for CSF dissemination and a benefit of "PNET-like" chemotherapy. The imaging appearance of GBM-PNET is not well-described and given areas of marked cellularity in the PNET components one might expect significantly reduced diffusion on MRI. The purpose of this study is to quantitatively evaluate the diffusion characteristics in GBM-PNET and compare them with conventional GBMs. Nine patients with surgical specimens yielding GBM-PNET were identified from the UCSF Pathology files. MR images of these patients were reviewed retrospectively. DWI (diffusion-weighted imaging) sequences were analyzed with multiple regions of interests placed within the tumor, and ADC (apparent diffusion coefficient) values were measured. Results were compared to previously published ADC values in pathology-proven conventional GBM cases from our institution. Reduced ADC was seen in GBM-PNET (mean 581 × 10(-6) mm(2)/s, range 338-817) compared to previously published mean of 1,030 × 10(-6) mm(2)/s in the enhancing components of conventional GBMs. We report substantially reduced ADC values in GBM-PNETs compared to conventional GBMs. If demonstrated in a larger sample, when areas of marked reduced diffusion are seen in a suspected GBM, MRI may appropriately direct tissue sampling and can advocate a thorough search for PNET-like components on histopathology. These patients may have a higher chance of developing CSF dissemination and may benefit from "PNET-like" platinum-based chemotherapy.

  20. Imp2 regulates GBM progression by activating IGF2/PI3K/Akt pathway.

    Science.gov (United States)

    Mu, Qingchun; Wang, Lijun; Yu, Fengbo; Gao, Haijun; Lei, Ting; Li, Peiwen; Liu, Pengfei; Zheng, Xu; Hu, Xitong; Chen, Yong; Jiang, Zhenfeng; Sayari, Arash J; Shen, Jia; Huang, Haiyan

    2015-01-01

    Glioblastomas multiforme (GBM) are the most frequently occurring malignant brain cancers. Treatment for GBM consists of surgical resection and subsequent adjuvant radiation therapy and chemotherapy. Despite this, GBM patient survival is limited to 12-15 months, and researchers are continually trying to develop improved therapy options. Insulin-like growth factor 2 mRNA-binding protein 2 (Imp2) is known to be upregulated in many cancers and is known to regulate the signaling activity of insulin-like growth factor 2 (IGF2). However, relatively little is known about its role in malignant development of GBM. In this study, we first found Imp2 is upregulated in GBM tissues by using clinical samples and public database search. Studies with loss and gain of Imp2 expression in in vitro GBM cell culture system demonstrated the role of Imp2 in promoting GBM cell proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT). Additionally, our results show that Imp2 regulates the activity of IGF2, which further activates PI3K/Akt signaling, thereby to promote GBM malignancy. Inhibition of Imp2 was also found to sensitize GBM to temozolomide treatment. These observations add to the current knowledge of GBM biology, and may prove useful in development of more effective GBM therapy.

  1. Bevacizumab (Avastin® no tratamento da membrana neovascular coroidal secundária à degeneração macular relacionada à idade: relato de caso Bevacizumab (Avastin® in treatment of choroidal neovascularization secondary to age-related macular degeneration: a case report

    Directory of Open Access Journals (Sweden)

    Tiago Eugênio Faria e Arantes

    2007-12-01

    Full Text Available As drogas anti-angiogênicas foram introduzidas recentemente no arsenal terapêutico das membranas neovasculares coroidais. O objetivo deste relato é descrever um caso de membranas neovasculares coroidais oculta com extenso descolamento do epitélio pigmentado da retina, tratada com bevacizumab (Avastin® intravítrea. A eficácia da medicação foi avaliada por meio da acuidade visual e de exames complementares (angiografia fluoresceínica, videoangiografia com indocianina verde e tomografia de coerência óptica. Após três injeções intravítreas de bevacizumab, obteve-se uma resposta anatômica e visual satisfatória, denotando benefícios da droga, apesar do extenso descolamento do epitélio pigmentado da retina associada a membranas neovasculares coroidais oculta.The antiangiogenic drugs have been recently introduced in the therapeutic armamentarium of choroidal neovascularization. The purpose of this report is to describe a case of occult choroidal neovascularization with extensive retinal pigment epithelial detachment treated with intravitreal bevacizumab (Avastin®. The efficacy of the medication was evaluated by means of visual acuity and complementary exams (fluorescein angiography, indocyanine green video angiography and optical coherence tomography. After three intravitreal injections of bevacizumab a satisfactory anatomic and visual response was achieved, showing benefits of the drug, despite the extensive retinal pigment epithelial detachment associated with occult choroidal neovascularization.

  2. Impact of oligodendroglial component in glioblastoma (GBM-O): Is the outcome favourable than glioblastoma?

    Science.gov (United States)

    Goda, Jayant S; Lewis, Shirley; Agarwal, Aditi; Epari, Sridhar; Churi, Shraddha; Padmavati, A; Gupta, Tejpal; Shetty, Prakash; Moiyadi, Aliasgar; Jalali, Rakesh

    2015-08-01

    Prognosis of patients with glioblastoma with oligodendroglial component (GBM-O) is not well defined. We report our experience of patients of GBM-O treated at our center. Between January 2007 and August 2013, out of 817 consecutive patients with glioblastoma (GBM), 74 patients with GBM-O were identified in our prospectively maintained database. An experienced neuropathologist revaluated the histopathology of all these 74 patients and the diagnosis of GBM-O was eventually confirmed in 57 patients. Patients were uniformly treated with maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolamide (TMZ). At a median follow up of 16 months, median overall survival (OS) and progression free survival (PFS) of the entire cohort was 23 months and 13 months respectively. Near total excision was performed in 30/57 (52.6%). On univariate analysis, age GBM-O patients with a similarly treated cohort of 105 GBM patients during the same period revealed significantly better median OS in favour of GBM-O (p = 0.01). Our experience suggests patients with GBM-O have a more favourable clinical outcome as compared to GBM. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Time Domain Astronomy with Fermi GBM in the Multi-messenger Era

    Science.gov (United States)

    Wilson-Hodge, Colleen A.; Fermi GBM team, GBM-LIGO team

    2018-01-01

    As the Multi-Messenger era begins with detections of gravitational waves with LIGO/Virgo and neutrinos with IceCube, the Fermi Gamma-ray Burst Monitor (GBM) provides context observations of gamma-ray transients between 8 keV and 40 MeV. Fermi GBM has a wide field of view, high uptime, and both in-orbit triggering and high time resolution continuous data enabling offline searches for weaker transients. GBM detects numerous gamma-ray bursts (GRBs), soft gamma-ray repeaters, X-ray bursters, solar flares and terrestrial gamma-ray flashes. Longer timescale transients, predominantly in our galaxy so far, are detected using the Earth occultation technique and epoch-folding for periodic sources. The GBM team has developed two ground-based searches to enhance detections of faint transients, especially short GRBs. The targeted search uses the time and location of an event detected with another instrument to coherently search the GBM data, increasing the sensitivity to a transient. The untargeted search agnostically searches the GBM data for all directions and times to find weaker transients. This search finds about 80 short GRBs per year, adding to the 40 per year triggered on-orbit. With its large field of view, high duty cycle and increasingly sophisticated detection methods, Fermi GBM is expected to have a major role in the Multi-Messenger era.

  4. Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.

    Science.gov (United States)

    van Daalen, Emma E; Jennette, J Charles; McAdoo, Stephen P; Pusey, Charles D; Alba, Marco A; Poulton, Caroline J; Wolterbeek, Ron; Nguyen, Tri Q; Goldschmeding, Roel; Alchi, Bassam; Griffiths, Meryl; de Zoysa, Janak R; Vincent, Beula; Bruijn, Jan A; Bajema, Ingeborg M

    2018-01-06

    Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 ( P =0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated ( P GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3. Copyright © 2018 by the American Society of Nephrology.

  5. TCGA Workshop: Genomics and Biology of Glioblastoma Multiforme (GBM) - TCGA

    Science.gov (United States)

    The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) held a workshop entitled, “Genomics and Biology of Glioblastoma Multiforme (GBM),” to review the initial GBM data from the TCGA pilot project.

  6. Visualizing molecular profiles of glioblastoma with GBM-BioDP.

    Directory of Open Access Journals (Sweden)

    Orieta Celiku

    Full Text Available Validation of clinical biomarkers and response to therapy is a challenging topic in cancer research. An important source of information for virtual validation is the datasets generated from multi-center cancer research projects such as The Cancer Genome Atlas project (TCGA. These data enable investigation of genetic and epigenetic changes responsible for cancer onset and progression, response to cancer therapies, and discovery of the molecular profiles of various cancers. However, these analyses often require bulk download of data and substantial bioinformatics expertise, which can be intimidating for investigators. Here, we report on the development of a new resource available to scientists: a data base called Glioblastoma Bio Discovery Portal (GBM-BioDP. GBM-BioDP is a free web-accessible resource that hosts a subset of the glioblastoma TCGA data and enables an intuitive query and interactive display of the resultant data. This resource provides visualization tools for the exploration of gene, miRNA, and protein expression, differential expression within the subtypes of GBM, and potential associations with clinical outcome, which are useful for virtual biological validation. The tool may also enable generation of hypotheses on how therapies impact GBM molecular profiles, which can help in personalization of treatment for optimal outcome. The resource can be accessed freely at http://gbm-biodp.nci.nih.gov (a tutorial is included.

  7. Quantitative Magnetization Transfer in Monitoring Glioblastoma (GBM) Response to Therapy.

    Science.gov (United States)

    Mehrabian, Hatef; Myrehaug, Sten; Soliman, Hany; Sahgal, Arjun; Stanisz, Greg J

    2018-02-06

    Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) response to chemo-radiation and identify the earliest time-point qMT could differentiate progressors from non-progressors. Nineteen GBM patients were recruited and MRI-scanned before (Day 0 ), two weeks (Day 14 ), and four weeks (Day 28 ) into the treatment, and one month after the end of the treatment (Day 70 ). Comprehensive qMT data was acquired, and a two-pool MT model was fit to the data. Response was determined at 3-8 months following the end of chemo-radiation. The amount of magnetization transfer ([Formula: see text]) was significantly lower in GBM compared to normal appearing white matter (p GBM are more sensitive to treatment effects compared to clinically used metrics. qMT could assess tumor aggressiveness and identify early progressors even before the treatment. Changes in qMT parameters within the first 14 days of the treatment were capable of separating early progressors from non-progressors, making qMT a promising biomarker to guide adaptive radiotherapy for GBM.

  8. The Second Fermi GBM Gamma-Ray Burst Catalog: The First Four Years

    NARCIS (Netherlands)

    von Kienlin, A.; Meegan, C.A.; Paciesas, W.S.; Bhat, P.N.; Bissaldi, E.; Briggs, M.S.; Burgess, J.M.; Byrne, D.; Chaplin, V.; Cleveland, W.; Connaughton, V.; Collazzi, A.C.; Fitzpatrick, G.; Foley, S.; Gibby, M.; Giles, M.; Goldstein, A.; Greiner, J.; Gruber, D.; Guiriec, S.; van der Horst, A.J.; Kouveliotou, C.; Layden, E.; McBreen, S.; McGlynn, S.; Pelassa, V.; Preece, R.D.; Rau, A.; Tierney, D.; Wilson-Hodge, C.A.; Xiong, S.; Younes, G.; Yu, H-F.

    2014-01-01

    This is the second of a series of catalogs of gamma-ray bursts (GRBs) observed with the Fermi Gamma-ray Burst Monitor (GBM). It extends the first two-year catalog by two more years, resulting in an overall list of 953 GBM triggered GRBs. The intention of the GBM GRB catalog is to provide information

  9. Fermi GBM Observations of Terrestrial Gamma Flashes

    Science.gov (United States)

    Wilson-Hodge, Colleen A.; Briggs, M. S.; Connaughton, V.; Fishman, G. J.; Bhat, P. N.; Paciesas, W. S.; Preece, R. D.; Kippen, R. M.; vonKienlin, A.; Dwyer, J. R.; hide

    2010-01-01

    In its first two years of operation, the Fermi Gamma Ray Burst Monitor (GBM) has observed 79 Terrestrial Gamma Flashes (TGFs). The thick Bismuth Germanate (BGO) detectors are excellent for TGF spectroscopy, having a high probability of recording the full energy of an incident photon, spanning a broad energy range from 150 keV to 40 MeV, and recording a large number of photons per TGF. Correlations between GBM TGF triggers and lightning sferics detected with the World-Wide Lightning Location Network indicate that TGFs and lightning are simultaneous to within tens of microseconds.

  10. All-Sky Monitoring of Variable Sources with Fermi GBM

    Science.gov (United States)

    Wilson-Hodge, Colleen A.; Cherry, Michael L.; Case, Gary L.; Camero-Arranz, Ascension; Chaplin, Vandiver; Connaughton, Valerie; Finger, Mark H.; Jenke, Pater; Rodi, James C.; Baumgartner, Wayne H.; hide

    2011-01-01

    This slide presentation reviews the monitoring of variable sources with the Fermi Gamma Ray Burst Monitor (GBM). It reviews the use of the Earth Occultation technique, the observations of the Crab Nebula with the GBM, and the comparison with other satellite's observations. The instruments on board the four satellites indicate a decline in the Crab from 2008-2010.

  11. Fully automatic GBM segmentation in the TCGA-GBM dataset: Prognosis and correlation with VASARI features.

    Science.gov (United States)

    Rios Velazquez, Emmanuel; Meier, Raphael; Dunn, William D; Alexander, Brian; Wiest, Roland; Bauer, Stefan; Gutman, David A; Reyes, Mauricio; Aerts, Hugo J W L

    2015-11-18

    Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. MRI sets of 109 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA). Spearman's correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Auto-segmented sub-volumes showed moderate to high agreement with manually delineated volumes (range (r): 0.4 - 0.86). Also, the auto and manual volumes showed similar correlation with VASARI features (auto r = 0.35, 0.43 and 0.36; manual r = 0.17, 0.67, 0.41, for contrast-enhancing, necrosis and edema, respectively). The auto-segmented contrast-enhancing volume and post-contrast abnormal volume showed the highest AUC (0.66, CI: 0.55-0.77 and 0.65, CI: 0.54-0.76), comparable to manually defined volumes (0.64, CI: 0.53-0.75 and 0.63, CI: 0.52-0.74, respectively). BraTumIA and manual tumor sub-compartments showed comparable performance in terms of prognosis and correlation with VASARI features. This method can enable more reproducible definition and quantification of imaging based biomarkers and has potential in high-throughput medical imaging research.

  12. In search of druggable targets for GBM amino acid metabolism

    NARCIS (Netherlands)

    Panosyan, Eduard H.; Lin, Henry J.; Koster, Jan; Lasky, Joseph L.

    2017-01-01

    Background: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database (http://r2.amc.nl) analyses were carried out to screen for such targets among 95 AA related enzymes. Methods: First, we identified the genes that were differentially

  13. Search for Gravitational Wave Counterparts with Fermi GBM

    Science.gov (United States)

    Hui, C. M.

    2017-01-01

    The progenitor of short gamma-ray bursts (GRBs) is believed to be the merger of two compact objects. This type of events will also produce gravitational waves. Since the gravitational waves discovery by LIGO, the search for a joint detection with an electromagnetic counterpart has been ongoing. Fermi GBM detects approximately 40 short GRBs per year, and we have been expanding our search looking for faint events in the GBM data that did not trigger onboard.

  14. THE FIVE YEAR FERMI/GBM MAGNETAR BURST CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Collazzi, A. C. [SciTec, Inc., 100 Wall Street, Princeton, NJ 08540 (United States); Kouveliotou, C.; Horst, A. J. van der; Younes, G. A. [Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052 (United States); Kaneko, Y.; Göğüş, E. [Sabancı University, Orhanlı-Tuzla, İstanbul 34956 (Turkey); Lin, L. [François Arago Centre, APC, 10 rue Alice Domon et Léonie Duquet, F-75205 Paris (France); Granot, J. [Department of Natural Sciences, The Open University of Israel, 1 University Road, P.O. Box 808, Raanana 43537 (Israel); Finger, M. H. [Universities Space Research Association, NSSTC, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Chaplin, V. L. [School of Medicine, Vanderbilt University, 1161 21st Avenue S, Nashville, TN 37232 (United States); Huppenkothen, D. [Center for Data Science, New York University, 726 Broadway, 7th Floor, New York, NY 10003 (United States); Watts, A. L. [Anton Pannekoek Institute, University of Amsterdam, Postbus 94249, 1090 GE Amsterdam (Netherlands); Kienlin, A. von [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Baring, M. G. [Department of Physics and Astronomy, Rice University, MS-108, P.O. Box 1892, Houston, TX 77251 (United States); Gruber, D. [Planetarium Südtirol, Gummer 5, I-39053 Karneid (Italy); Bhat, P. N. [CSPAR, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States); Gibby, M. H., E-mail: acollazzi@scitec.com [Jacobs Technology, Inc., Huntsville, AL (United States); and others

    2015-05-15

    Since launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has detected many hundreds of bursts from magnetar sources. While the vast majority of these bursts have been attributed to several known magnetars, there is also a small sample of magnetar-like bursts of unknown origin. Here, we present the Fermi/GBM magnetar catalog, providing the results of the temporal and spectral analyses of 440 magnetar bursts with high temporal and spectral resolution. This catalog covers the first five years of GBM magnetar observations, from 2008 July to 2013 June. We provide durations, spectral parameters for various models, fluences, and peak fluxes for all the bursts, as well as a detailed temporal analysis for SGR J1550–5418 bursts. Finally, we suggest that some of the bursts of unknown origin are associated with the newly discovered magnetar 3XMM J185246.6+0033.7.

  15. Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics.

    Science.gov (United States)

    St-Coeur, Patrick-Denis; Poitras, Julie J; Cuperlovic-Culf, Miroslava; Touaibia, Mohamed; Morin, Pier

    2015-10-01

    Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Current therapeutic approach to treat this malignancy involves a combination of surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms contributing to inherent and acquired resistance to this chemotherapeutic agent have been identified and can lead to treatment failure. This study undertook a metabolomics-based approach to characterize the metabolic profiles observed in temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a small sub-set of primary GBM tumors. This approach was also utilized to explore the metabolic changes modulated upon cell treatment with temozolomide and lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential. Metabolites previously explored for their potential role in chemoresistance including glucose, citrate and isocitrate demonstrated elevated levels in temozolomide-resistant GBM cells. In addition, a signature of metabolites comprising alanine, choline, creatine and phosphorylcholine was identified as up-regulated in sensitive GBM cell line across different treatments. These results present the metabolic profiles associated with temozolomide response in selected GBM models and propose interesting leads that could be leveraged for the development of therapeutic or diagnostic tools to impact temozolomide response in GBMs.

  16. 40 CFR 180.1097 - GBM-ROPE; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false GBM-ROPE; exemption from the... Exemptions From Tolerances § 180.1097 GBM-ROPE; exemption from the requirement of a tolerance. The grape berry moth pheromone (GBM-ROPE) containing the active ingredients (Z)-9-dedecenyl acetate and (Z)-11...

  17. Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE.

    Science.gov (United States)

    Alexander, Brian M; Ba, Sujuan; Berger, Mitchel S; Berry, Donald A; Cavenee, Webster K; Chang, Susan M; Cloughesy, Timothy F; Jiang, Tao; Khasraw, Mustafa; Li, Wenbin; Mittman, Robert; Poste, George H; Wen, Patrick Y; Yung, W K Alfred; Barker, Anna D

    2018-02-15

    Glioblastoma (GBM) is a deadly disease with few effective therapies. Although much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is composed of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage to support registration. Therapeutic arms with biomarkers may be added to the trial over time, while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice. Clin Cancer Res; 24(4); 737-43. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Validation of an imageable surgical resection animal model of Glioblastoma (GBM).

    Science.gov (United States)

    Sweeney, Kieron J; Jarzabek, Monika A; Dicker, Patrick; O'Brien, Donncha F; Callanan, John J; Byrne, Annette T; Prehn, Jochen H M

    2014-08-15

    Glioblastoma (GBM) is the most common and malignant primary brain tumour having a median survival of just 12-18 months following standard therapy protocols. Local recurrence, post-resection and adjuvant therapy occurs in most cases. U87MG-luc2-bearing GBM xenografts underwent 4.5mm craniectomy and tumour resection using microsurgical techniques. The cranial defect was repaired using a novel modified cranial window technique consisting of a circular microscope coverslip held in place with glue. Immediate post-operative bioluminescence imaging (BLI) revealed a gross total resection rate of 75%. At censor point 4 weeks post-resection, Kaplan-Meier survival analysis revealed 100% survival in the surgical group compared to 0% in the non-surgical cohort (p=0.01). No neurological defects or infections in the surgical group were observed. GBM recurrence was reliably imaged using facile non-invasive optical bioluminescence (BLI) imaging with recurrence observed at week 4. For the first time, we have used a novel cranial defect repair method to extend and improve intracranial surgical resection methods for application in translational GBM rodent disease models. Combining BLI and the cranial window technique described herein facilitates non-invasive serial imaging follow-up. Within the current context we have developed a robust methodology for establishing a clinically relevant imageable GBM surgical resection model that appropriately mimics GBM recurrence post resection in patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance.

    Science.gov (United States)

    Lee, Jin-Ku; Chang, Nakho; Yoon, Yeup; Yang, Heekyoung; Cho, Heejin; Kim, Eunhee; Shin, Yongjae; Kang, Wonyoung; Oh, Young Taek; Mun, Gyeong In; Joo, Kyeung Min; Nam, Do-Hyun; Lee, Jeongwu

    2016-01-01

    Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. USP1 was highly expressed in gliomas relative to normal brain tissues and more preferentially in GSC enrichment marker (CD133 or CD15) positive cells. USP1 positively regulated the protein stability of the ID1 and CHEK1, critical regulators of DNA damage response and stem cell maintenance. Targeting USP1 by RNA interference or treatment with a chemical USP1 inhibitor attenuated clonogenic growth and survival of GSCs and enhanced radiosensitivity of GBM cells. Finally, USP1 inhibition alone or in combination with radiation significantly prolonged the survival of tumor-bearing mice. USP1-mediated protein stabilization promotes GSC maintenance and treatment resistance, thereby providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM. © The Author(s) 2015. 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.

  20. The Fermi GBM and LAT follow-up of GW150914

    Directory of Open Access Journals (Sweden)

    Bissaldi E.

    2017-01-01

    Here we present observations by the Fermi Gamma-Ray BurstMonitor (GBM [1] and by the Large Area Telescope (LAT [2] of the LIGO Gravitational Wave event GW150914, which has been associated to the merger of two stellar-mass BHs. We report the presence of a weak transient event in GBM data, close in time to the LIGO one. We discuss the characteristics of this GBM transient, which are consistent with a weak short GRB arriving at a large angle to the direction in which Fermi was pointing. Furthermore, we report LAT upper limits (ULs for GW150914, and we present the strategy for follow-up observations of GW events with the LAT.

  1. An exploration of counterfeit medicine surveillance strategies guided by geospatial analysis: lessons learned from counterfeit Avastin detection in the US drug supply chain.

    Science.gov (United States)

    Cuomo, Raphael E; Mackey, Tim K

    2014-12-02

    To explore healthcare policy and system improvements that would more proactively respond to future penetration of counterfeit cancer medications in the USA drug supply chain using geospatial analysis. A statistical and geospatial analysis of areas that received notices from the Food and Drug Administration (FDA) about the possibility of counterfeit Avastin penetrating the US drug supply chain. Data from FDA warning notices were compared to data from 44 demographic variables available from the US Census Bureau via correlation, means testing and geospatial visualisation. Results were interpreted in light of existing literature in order to recommend improvements to surveillance of counterfeit medicines. This study analysed 791 distinct healthcare provider addresses that received FDA warning notices across 30,431 zip codes in the USA. Statistical outputs were Pearson's correlation coefficients and t values. Geospatial outputs were cartographic visualisations. These data were used to generate the overarching study outcome, which was a recommendation for a strategy for drug safety surveillance congruent with existing literature on counterfeit medication. Zip codes with greater numbers of individuals age 65+ and greater numbers of ethnic white individuals were most correlated with receipt of a counterfeit Avastin notice. Geospatial visualisations designed in conjunction with statistical analysis of demographic variables appeared more capable of suggesting areas and populations that may be at risk for undetected counterfeit Avastin penetration. This study suggests that dual incorporation of statistical and geospatial analysis in surveillance of counterfeit medicine may be helpful in guiding efforts to prevent, detect and visualise counterfeit medicines penetrations in the US drug supply chain and other settings. Importantly, the information generated by these analyses could be utilised to identify at-risk populations associated with demographic characteristics

  2. EVA1A inhibits GBM cell proliferation by inducing autophagy and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xue; Kan, Shifeng; Liu, Zhen [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Guang [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 (Singapore); Zhang, Xiaoyan [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Chen, Yingyu [Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Peking University Center for Human Disease Genomics, Beijing 100191 (China); Bai, Yun, E-mail: baiyun@bjmu.edu.cn [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2017-03-01

    Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner. EVA1A-mediated autophagy was associated with inactivation of the mTOR/RPS6KB1 signaling pathway. Furthermore in vivo, overexpression of EVA1A successfully inhibited tumor growth in NOD/SCID mice. Our data suggest that EVA1A-induced autophagy and apoptosis play a role in suppressing the development of GBM and their up-regulation may be an effective method for treating this form of cancer. - Highlights: • Overexpression of EVA1A suppresses GBM cell growth. • EVA1A induces autophagy through the mTOR/RPS6KB1 pathway. • EVA1A induces GBM cell apoptosis. • EVA1A inhibits the development of GBM in vivo.

  3. A Large-Scale RNAi Screen Identifies SGK1 as a Key Survival Kinase for GBM Stem Cells.

    Science.gov (United States)

    Kulkarni, Shreya; Goel-Bhattacharya, Surbhi; Sengupta, Sejuti; Cochran, Brent H

    2018-01-01

    Glioblastoma multiforme (GBM) is the most common type of primary malignant brain cancer and has a very poor prognosis. A subpopulation of cells known as GBM stem-like cells (GBM-SC) have the capacity to initiate and sustain tumor growth and possess molecular characteristics similar to the parental tumor. GBM-SCs are known to be enriched in hypoxic niches and may contribute to therapeutic resistance. Therefore, to identify genetic determinants important for the proliferation and survival of GBM stem cells, an unbiased pooled shRNA screen of 10,000 genes was conducted under normoxic as well as hypoxic conditions. A number of essential genes were identified that are required for GBM-SC growth, under either or both oxygen conditions, in two different GBM-SC lines. Interestingly, only about a third of the essential genes were common to both cell lines. The oxygen environment significantly impacts the cellular genetic dependencies as 30% of the genes required under hypoxia were not required under normoxic conditions. In addition to identifying essential genes already implicated in GBM such as CDK4, KIF11 , and RAN , the screen also identified new genes that have not been previously implicated in GBM stem cell biology. The importance of the serum and glucocorticoid-regulated kinase 1 (SGK1) for cellular survival was validated in multiple patient-derived GBM stem cell lines using shRNA, CRISPR, and pharmacologic inhibitors. However, SGK1 depletion and inhibition has little effect on traditional serum grown glioma lines and on differentiated GBM-SCs indicating its specific importance in GBM stem cell survival. Implications: This study identifies genes required for the growth and survival of GBM stem cells under both normoxic and hypoxic conditions and finds SGK1 as a novel potential drug target for GBM. Mol Cancer Res; 16(1); 103-14. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an international multicenter study.

    Science.gov (United States)

    Mahler, Michael; Radice, Antonella; Sinico, Renato A; Damoiseaux, Jan; Seaman, Andrea; Buckmelter, Kristen; Vizjak, Alenka; Buchner, Carol; Binder, Walter L; Fritzler, Marvin J; Cui, Zhao

    2012-01-01

    Autoantibodies to the non-collagen region (NC1) of the alpha-3 subunit of collagen IV represent a serological hallmark in the diagnosis of Goodpasture's syndrome (GPS). The objective of our study was to carefully analyze the performance characteristics of a novel anti-glomerular basement membrane (GBM) chemiluminescence immunoassay (CIA). Sera from patients with GPS (n = 90) were collected from four clinical centers. Samples from different disease groups (n = 397) and healthy individuals (n = 400) were used as controls. All samples were tested for anti-GBM antibodies by a rapid, random access CIA (QUANTA Flash™ GBM). Most of the samples were also tested using other methods including different commercial anti-GBM IgG assays and research assays for anti-GBM IgA and IgM. The sensitivity and specificity of the novel CIA was 95.6% [95% confidence interval (CI) 89.0-98.8%] and 99.6% (95% CI 98.9-99.9%), respectively. Receiver operating characteristic analysis showed good discrimination between GPS patients and controls. The area under the curve was 0.98 (CI 0.96-1.0). The three anti-GBM antibody-positive samples from the control group were from two healthy individuals and one human immunodeficiency virus (HIV)-infected patient. All three individuals had low levels of anti-GBM antibodies [20, 24 and 25 chemiluminescent unit (CU), cutoff 20 CU]. When the results of the new CIA were compared to other methods, good agreement was observed: 95.8% (kappa = 0.92) versus EliA™ GBM, 97.4% (kappa = 0.95) versus both BINDAZYME™ Anti-GBM and QUANTA Lite® GBM. Anti-GBM IgA was detectable in low concentrations in patients with GPS and was associated with anti-GBM IgG but was less useful in discriminating GPS patients and controls. No discrimination was found for anti-GBM IgM. The novel QUANTA Flash™ GBM CIA demonstrated good sensitivity and specificity and had good agreement with other methods. Our data confirm that ∼5% of patients with GPS do not have detectable levels of

  5. The Fermi GBM Gamma-Ray Burst Catalog: The First Two Years

    NARCIS (Netherlands)

    Paciesas, W.S.; Meegan, C.A.; von Kienlin, A.; Bhat, P.N.; Bissaldi, E.; Briggs, M.S.; M. Burgess, J.; Chaplin, V.; Connaughton, V.; Diehl, R.; Fishman, G.J.; Fitzpatrick, G.; Foley, S.; H. Gibby, M.; Giles, M.; Goldstein, A.; Greiner, J.; Gruber, D.; Guiriec, S.; van der Horst, A.J.; Kippen, R.M.; Kouveliotou, C.; Lichti, G.; Lin, L.; McBreen, S.; Preece, R.D.; Rau, A.; Tierney, D.; Wilson-Hodge, C.

    2012-01-01

    The Fermi Gamma-ray Burst Monitor (GBM) is designed to enhance the scientific return from Fermi in studying gamma-ray bursts (GRBs). In its first two years of operation GBM triggered on 491 GRBs. We summarize the criteria used for triggering and quantify the general characteristics of the triggered

  6. Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

    Science.gov (United States)

    Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

    2017-11-10

    Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

  7. Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).

    Science.gov (United States)

    Elkamhawy, Ahmed; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Kim, Hyeon Young; Heo, Jin-Chul; Park, Woo-Kyu; Lee, Chong-Ock; Yang, Heekyoung; Kim, Kang Ho; Nam, Do-Hyun; Seol, Ho Jun; Cho, Heeyeong; Roh, Eun Joo

    2015-10-20

    Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC₅₀ values were exhibited over a panel of three primary GBM patient-derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Fermi GBM Observations of LIGO Gravitational-Wave Event Gw150914

    Science.gov (United States)

    Connaughton, V.; Burns, E.; Goldstein, A.; Blackburn, L.; Briggs, M. S.; Zhang, B.-B.; Camp, J.; Christensen, N.; Hui, C. M.; Jenke, P.; hide

    2016-01-01

    With an instantaneous view of 70% of the sky, the Fermi Gamma-ray Burst Monitor (GBM) is an excellent partner in the search for electromagnetic counterparts to gravitational-wave (GW) events. GBM observations at the time of the Laser Interferometer Gravitational-wave Observatory (LIGO) event GW150914 reveal the presence of a weak transient above 50 keV, 0.4 s after the GW event, with a false-alarm probability of 0.0022 (2.9(sigma)). This weak transient lasting 1 s was not detected by any other instrument and does not appear to be connected with other previously known astrophysical, solar, terrestrial, or magnetospheric activity. Its localization is ill-constrained but consistent with the direction of GW150914. The duration and spectrum of the transient event are consistent with a weak short gamma-ray burst (GRB) arriving at a large angle to the direction in which Fermi was pointing where the GBM detector response is not optimal. If the GBM transient is associated with GW150914, then this electromagnetic signal from a stellar mass black hole binary merger is unexpected. We calculate a luminosity in hard X-ray emission between 1 keV and 10 MeV of 1.8(sup +1.5, sub -1.0) x 10(exp 49) erg/s. Future joint observations of GW events by LIGO/Virgo and Fermi GBM could reveal whether the weak transient reported here is a plausible counterpart to GW150914 or a chance coincidence, and will further probe the connection between compact binary mergers and short GRBs.

  9. Dismantling of the EB experiment: Experimental research on the retrieved GBM and bentonite blocks

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jiang-Feng, E-mail: jeafliu@hotmail.com [State Key Laboratory for Geomchanics & Deep Underground Engineering, and School of Mechanics and Civil Engineering, China University of Mining & Technology, Xuzhou, Jiangsu 221116 (China); Laboratoire de Méchanique de Lille (LML), and École Centrale de Lille, BP 48, F-59651 Villeneuve d’Ascq Cedex (France); Skoczylas, Frédéric [Laboratoire de Méchanique de Lille (LML), and École Centrale de Lille, BP 48, F-59651 Villeneuve d’Ascq Cedex (France); Talandier, Jean [ANDRA, 1-7 rue Jean Monnet, 92298 Châtenay-Malabry Cedex (France); Pu, Hai [State Key Laboratory for Geomchanics & Deep Underground Engineering, and School of Mechanics and Civil Engineering, China University of Mining & Technology, Xuzhou, Jiangsu 221116 (China)

    2016-04-15

    Graphical abstract: - Highlights: • We present a demonstration of a new concept of HLW (high-level waste) repositories. • The hydro-mechanical characteristics of GBM and blocks were determined. • The water retention curves (WRCs) of GBM and blocks were presented. • The effective gas permeability of the GBM and blocks were measured. • The homogeneity of the GBM and blocks were investigated. - Abstract: The Engineered Barrier Emplacement Experiment in Opalinus Clay (EB experiment) was a full-scale test for the demonstration of a new concept of high-level waste (HLW) repositories in horizontal drifts in the Opalinus Clay formation. After 10.5 years of hydration, the EB experiment was dismantled in autumn 2012. Samples obtained from the granular bentonite material (GBM), and bentonite blocks were sent to a laboratory for further analysis. The bentonite samples analyzed at the Laboratory of Mechanic of Lille (LML) were obtained from the CMT1, CMT2, CMT3 and RW sections. Their physical states were determined, as were their effective gas permeability and swelling capacity at different relative humidity (RH) levels. The results indicate that the water contents of the GBM determined in the laboratory ranged between 25.63% and 44.88% and that the dry densities ranged between 1.13 and 1.44 g/cm{sup 3}. The blocks had water contents similar to (or slightly higher than) those of the GBM, and their dry densities had decreased from an initial value of 1.69 g/cm{sup 3} to values close to 1.30 g/cm{sup 3}, which were similar to the average values found in the GBM. The effective gas permeabilities of the GBM samples were within the range of 1.50 × 10{sup −22} m{sup 2} and 1.03 × 10{sup −17} m{sup 2}, whereas, the corresponding values of the samples obtained from the blocks were between 2.20 × 10{sup −21} m{sup 2} and 5.12 × 10{sup −21} m{sup 2}. The permeability values are primarily related to the dry densities and water contents of the samples. Contact with

  10. Using GRB 080723B to cross-calibrate Fermi/GBM and INTEGRAL

    International Nuclear Information System (INIS)

    Kienlin, A. von; Briggs, M. S.; Connoughton, V.; Preece, R. D.; McBreen, S.; Sazonov, Sergey; Tsygankov, Sergey; Wilson-Hodge, C. A.

    2009-01-01

    On July 23, 2008 GRB 080723B, a bright GRB lasting about 105 s was detected by the INTEGRAL burst alert system. This burst was also detected by the Fermi Gamma-ray burst monitor. At this time no Fermi/GBM GCN notices were distributed to the public because Fermi was still in commissioning phase. The simultaneous detection of a bright GRB by both satellites gives us the opportunity to cross-calibrate the GBM with the already well-calibrated instruments on-board INTEGRAL, the Spectrometer SPI and the Imager IBIS. Time-resolved spectroscopy of this long and structured GRB is of special importance because Fermi was slewing during the GRB was still ongoing. In this paper we present a first and still preliminary analysis of the GBM spectra and compare them to those obtained by SPI for the same selection of time intervals. A more accurate cross-calibration will be forthcoming when the improved in-flight calibration of GBM is available and the corresponding data and responses can be reprocessed.

  11. THE THIRD FERMI GBM GAMMA-RAY BURST CATALOG: THE FIRST SIX YEARS

    International Nuclear Information System (INIS)

    Bhat, P. Narayana; Meegan, Charles A.; Briggs, Michael S.; Burns, Eric; Chaplin, Vandiver; Fitzpatrick, Gerard; Jenke, Peter A.; Von Kienlin, Andreas; Greiner, Jochen; Paciesas, William S.; Cleveland, William H.; Connaughton, Valerie; Burgess, J. Michael; Collazzi, Andrew C.; Diekmann, Anne M.; Gibby, Melissa H.; Giles, Misty M.; Goldstein, Adam M.; Kippen, R. Marc; Kouveliotou, Chryssa

    2016-01-01

    Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two γ -ray bursts (GRBs) every three days. Here, we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years through the middle of 2014 July. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM-detected GRBs. For each GRB, the location and main characteristics of the prompt emission, the duration, peak flux, and fluence are derived. The latter two quantities are calculated for the 50–300 keV energy band where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10 to 1000 keV, exploiting the full energy range of GBM's low-energy [Nai[Tl)] detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fit by a two-component model with short-hard and long-soft bursts than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.

  12. THE THIRD FERMI GBM GAMMA-RAY BURST CATALOG: THE FIRST SIX YEARS

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, P. Narayana; Meegan, Charles A.; Briggs, Michael S.; Burns, Eric; Chaplin, Vandiver; Fitzpatrick, Gerard; Jenke, Peter A. [The Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Von Kienlin, Andreas; Greiner, Jochen [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Paciesas, William S.; Cleveland, William H.; Connaughton, Valerie [Universities Space Research Association, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Burgess, J. Michael [The Oskar Klein Centre for Cosmoparticle Physics, AlbaNova, SE-106 91 Stockholm (Sweden); Collazzi, Andrew C. [SciTec Inc., 100 Wall Street, Princeton NJ, 08540 (United States); Diekmann, Anne M.; Gibby, Melissa H.; Giles, Misty M. [Jacobs Technology, Inc., Huntsville, Alabama (United States); Goldstein, Adam M. [ZP12 Astrophysics Office, NASA-Marshall Space Flight Center, Huntsville, AL 35812 (United States); Kippen, R. Marc [Los Alamos National Laboratory, MS B244, P.O. Box 1663, Los Alamos, NM 87545 (United States); Kouveliotou, Chryssa [Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052 (United States); and others

    2016-04-01

    Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two γ -ray bursts (GRBs) every three days. Here, we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years through the middle of 2014 July. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM-detected GRBs. For each GRB, the location and main characteristics of the prompt emission, the duration, peak flux, and fluence are derived. The latter two quantities are calculated for the 50–300 keV energy band where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10 to 1000 keV, exploiting the full energy range of GBM's low-energy [Nai[Tl)] detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fit by a two-component model with short-hard and long-soft bursts than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.

  13. The Latest Space-Borne Observations of TGFs from Fermi-GBM

    Science.gov (United States)

    Fishman, Gerald J.

    2010-01-01

    The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) is detecting about two TGFs per week. This rate has increased by a factor of approx.eight since launch when flight software was uploaded to the spacecraft in November 2009 in order to increase the sensitivity of GBM to TGFs. Weaker, un-triggered TGFs are now also being observed about once per day over selected low-latitude regions Americas. The high efficiency and time resolution (2 s) of GBM allows temporal features to be resolved so that some insight may be gained on the origin and transport of the gamma-ray photons through the atmosphere. TGFs are observed to be shorter than previously thought, with an average duration of approx.100 micro-s. The absolute times of TGFs are known to approx.10 micro-s, allowing accurate correlations of TGFs with lightning networks and other lightning-related phenomena. The events are observed in the thick bismuth germanate (BGO) scintillation detectors of GBM with photon energies above 40 MeV. Other new results on the temporal and spectral characteristics of TGFs will be presented, along with properties of several electron-positron TGF events that have been identified.

  14. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool.

    Science.gov (United States)

    Manterola, Lorea; Guruceaga, Elizabeth; Gállego Pérez-Larraya, Jaime; González-Huarriz, Marisol; Jauregui, Patricia; Tejada, Sonia; Diez-Valle, Ricardo; Segura, Victor; Samprón, Nicolás; Barrena, Cristina; Ruiz, Irune; Agirre, Amaia; Ayuso, Angel; Rodríguez, Javier; González, Alvaro; Xipell, Enric; Matheu, Ander; López de Munain, Adolfo; Tuñón, Teresa; Zazpe, Idoya; García-Foncillas, Jesús; Paris, Sophie; Delattre, Jean Yves; Alonso, Marta M

    2014-04-01

    Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients. To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients. We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis. Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.

  15. Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

    Science.gov (United States)

    Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

    2014-02-01

    Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

  16. GBM-associated mutations and altered protein expression are more common in young patients.

    Science.gov (United States)

    Ferguson, Sherise D; Xiu, Joanne; Weathers, Shiao-Pei; Zhou, Shouhao; Kesari, Santosh; Weiss, Stephanie E; Verhaak, Roeland G; Hohl, Raymond J; Barger, Geoffrey R; Reddy, Sandeep K; Heimberger, Amy B

    2016-10-25

    Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age ≥ 70) and younger (18 GBM cohort compared to the older cohort (P GBM cohort, younger patients had significantly more mutations in PDGFRA, PTPN11, SMARCA4, BRAF and TP53. GBMs from 178 elderly patients and 197 young patients were analyzed using DNA sequencing, immunohistochemistry, in situ hybridization, and MGMT-methylation assay to ascertain mutational and amplification/expressional status. Significant molecular differences occurred in GBMs from elderly and young patients. Except for the older cohort's more frequent PTEN mutation and MGMT methylation, younger patients had a higher frequency of potential therapeutic targets.

  17. Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM : Bone marrow derived cell in GBM

    NARCIS (Netherlands)

    Boer, Jennifer C.; Walenkamp, Annemiek M. E.; den Dunnen, Wilfred F. A.

    2014-01-01

    Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for

  18. Performance of two strategies for urgent ANCA and anti-GBM analysis in vasculitis.

    Science.gov (United States)

    de Joode, Anoek A E; Roozendaal, Caroline; van der Leij, Marcel J; Bungener, Laura B; Sanders, Jan Stephan F; Stegeman, Coen A

    2014-02-01

    In anti-neutrophil cytoplasmic antibodies (ANCA) associated small vessel vasculitis (AAV), rapid testing for ANCA and anti-glomerular basement membrane (GBM) antibodies may be beneficial for therapeutic purpose. We analysed the diagnostic performance of two rapid ANCA and anti-GBM test methods in 260 patients with suspected AAV. Between January 2004 and November 2010, we analysed 260 samples by qualitative Dotblot (Biomedical Diagnostics); retrospective analysis followed with directly coated highly sensitive automated Phadia ELiA and ELiA anti-GBM. Results were related to the final clinical diagnosis and compared with routine capture ELISA. Seventy-four patients had a final diagnosis of AAV (n=62) or anti-GBM disease (n=12). Both Dotblot and ELiA detected all 12 cases of anti-GBM disease; 2 false positive results were found. Dotblot detected ANCA in 56 of 62 AAV patients (sensitivity 90%, NPV 97%), and showed 5 false positives (specificity 97%, PPV 90%). The Phadia ELiA anti-PR3(s) or anti-MPO(s) was positive in 57 of 62 AAV patients (sensitivity 92%, NPV 97%), and had 5 false positives (specificity 97%, PPV 88%). Routine capture ELISA was equally accurate (sensitivity 94%, specificity 97%, PPV 88%, NPV 98%). The Dotblot and Phadia ELiA on anti-GBM, anti-PR3(s) and anti-MPO(s) performed excellently; results were almost identical to routine ELISA. When suspicion of AAV or anti-GBM disease is high and diagnosis is urgently needed, both tests are very powerful for rapid serological diagnosis. Further studies have to confirm the test performances in samples routinely presented for ANCA testing and in follow-up of positive patients. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  19. The Interplanetary Network Supplement to the Fermi GBM Catalog - An AO-2 and AO-3 Guest Investigator Project

    Science.gov (United States)

    Hurley, K.; Briggs, M.; Connaughton, V.; Meegan, C.; von Kienlin, A.; Rau, A.; Zhang, X.; Golenetskii, S.; Aptekar, R.; Mazets, E.; hide

    2012-01-01

    In the first two years of operation of the Fermi GBM, the 9-spacecraft Interplanetary Network (IPN) detected 158 GBM bursts with one or two distant spacecraft, and triangulated them to annuli or error boxes. Combining the IPN and GBM localizations leads to error boxes which are up to 4 orders of magnitude smaller than those of the GBM alone. These localizations comprise the IPN supplement to the GBM catalog, and they support a wide range of scientific investigations.

  20. Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma.

    Science.gov (United States)

    Hicks, Martin J; Funato, Kosuke; Wang, Lan; Aronowitz, Eric; Dyke, Jonathan P; Ballon, Douglas J; Havlicek, David F; Frenk, Esther Z; De, Bishnu P; Chiuchiolo, Maria J; Sondhi, Dolan; Hackett, Neil R; Kaminsky, Stephen M; Tabar, Viviane; Crystal, Ronald G

    2015-01-01

    The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.

  1. DW-MRI as a Predictive Biomarker of Radiosensitization of GBM through Targeted Inhibition of Checkpoint Kinases.

    Science.gov (United States)

    Williams, Terence M; Galbán, Stefanie; Li, Fei; Heist, Kevin A; Galbán, Craig J; Lawrence, Theodore S; Holland, Eric C; Thomae, Tami L; Chenevert, Thomas L; Rehemtulla, Alnawaz; Ross, Brian D

    2013-04-01

    The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms including checkpoint kinase (Chk1/2)-mediated increased DNA repair capability, which can attenuate the effects of genotoxic chemotherapies and radiation. The goal of this study was to evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a biomarker for Chk1/2 inhibitors in combination with radiation for enhancement of treatment efficacy in GBM. We evaluated a specific small molecule inhibitor of Chk1/2, AZD7762, in combination with radiation using in vitro human cell lines and in vivo using a genetically engineered GBM mouse model. DW-MRI and T1-contrast MRI were used to follow treatment effects on intracranial tumor cellularity and growth rates, respectively. AZD7762 inhibited clonal proliferation in a panel of GBM cell lines and increased radiosensitivity in p53-mutated GBM cell lines to a greater extent compared to p53 wild-type cells. In vivo efficacy of AZD7762 demonstrated a dose-dependent inhibitory effect on GBM tumor growth rate and a reduction in tumor cellularity based on DW-MRI scans along with enhancement of radiation efficacy. DW-MRI was found to be a useful imaging biomarker for the detection of radiosensitization through inhibition of checkpoint kinases. Chk1/2 inhibition resulted in antiproliferative activity, prevention of DNA damage-induced repair, and radiosensitization in preclinical GBM tumor models, both in vitro and in vivo. The effects were found to be maximal in p53-mutated GBM cells. These results provide the rationale for integration of DW-MRI in clinical translation of Chk1/2 inhibition with radiation for the treatment of GBM.

  2. Rituximab in anti-GBM disease: A retrospective study of 8 patients.

    Science.gov (United States)

    Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

    2015-06-01

    Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Finding Sub-threshold Short Gamma-ray Bursts in Fermi GBM Data

    Science.gov (United States)

    Burns, Eric; Fermi Gamma-ray Burst Monitor Team

    2018-01-01

    The all-sky monitoring capability of Fermi GBM makes it ideal for finding transients, and the most prolific detector of short gamma-ray bursts with about 40 on-board triggers per year. Because the observed brightness of short gamma-ray bursts has no correlation with redshift, weak short gamma-ray bursts are important during the gravitational wave era. With this in mind, we discuss two searches of GBM data to find short gamma-ray which were below the on-board trigger threshold. The untargeted search looks for significant background-subtracted signals in two or more detectors at various timescales in the continuous data, detecting ~80 additional short GRB candidates per year. The targeted search is the most sensitive search for weak gamma-ray signals in GBM data and is run over limited time intervals around sources of interest like gravitational waves.

  4. Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors.

    Science.gov (United States)

    Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

    2018-04-08

    Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-β₁ and -β₂ levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-β₁ significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

  5. Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors

    Directory of Open Access Journals (Sweden)

    Laurent-Olivier Roy

    2018-04-01

    Full Text Available Glioblastoma (GBM represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β. We hypothesized that TGF-β gene expression could correlate with overall survival (OS and serve as a prognostic biomarker. TGF-β1 and -β2 expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan–Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS. In GBM, TGF-β1 and -β2 levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan–Meier and multivariate analyses revealed that high to moderate expressions of TGF-β1 significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β1 is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β2. We believe our study is the first to unveil a significant relationship between TGF-β1 expression and OS or PFS in newly diagnosed GBM. TGF-β1 could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

  6. Photospheric Emission in the Joint GBM and Konus Prompt Spectra of GRB 120323A

    Energy Technology Data Exchange (ETDEWEB)

    Guiriec, S.; Kouveliotou, C. [Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052 (United States); Gehrels, N.; McEnery, J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Hartmann, D. H., E-mail: sylvain.guiriec@nasa.gov [Department of Physics and Astronomy, Clemson University, Kinard Lab of Physics (United States)

    2017-09-10

    GRB 120323A is a very intense short gamma -ray burst (GRB) detected simultaneously during its prompt γ -ray emission phase with the Gamma-ray Burst Monitor (GBM) on board the Fermi Gamma-ray Space Telescope and the Konus experiment on board the Wind satellite. GBM and Konus operate in the keV–MeV regime; however, the GBM range is broader toward both the low and the high parts of the γ -ray spectrum. Analyses of such bright events provide a unique opportunity to check the consistency of the data analysis as well as cross-calibrate the two instruments. We performed time-integrated and coarse time-resolved spectral analysis of GRB 120323A prompt emission. We conclude that the analyses of GBM and Konus data are only consistent when using a double-hump spectral shape for both data sets; in contrast, the single hump of the empirical Band function, traditionally used to fit GRB prompt emission spectra, leads to significant discrepancies between GBM and Konus analysis results. Our two-hump model is a combination of a thermal-like and a non-thermal component. We interpret the first component as a natural manifestation of the jet photospheric emission.

  7. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

    Science.gov (United States)

    Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

    2011-11-15

    The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

  8. Observations of Accreting Pulsars with the FERMI-GBM

    Science.gov (United States)

    Wilson-Hodge, Colleen

    2012-01-01

    The Gamma-ray Burst Monitor (GBM) on-board Fermi comprises 12 NaI detectors spanning the 8-1000 keV band and 2 BGO detectors spanning the 100 keV to 40 MeV band. These detectors view the entire unocculted sky, providing long (approximately 40 ks/day) observations of accreting pulsars daily, which allow long-term monitoring of spin-frequencies and pulsed uxes via epoch-folded searches plus daily blind searches for new pulsars. Phase averaged uxes can be measured using the Earth occultation technique. In this talk I will present highlights of GBM accretion-powered pulsar monitoring such as the discovery of a torque reversal in 4U1626-67, a high-energy QPO in A0535+26, and evidence for a stable accretion disk in OAO 1657-415.

  9. The Fermi Gamma-ray Burst Monitor (GBM) Terrestrial Gamma-ray Flash (TGF) Catalog

    Science.gov (United States)

    Briggs, M. S.; Roberts, O.; Fitzpatrick, G.; Stanbro, M.; Cramer, E.; Mailyan, B. G.; McBreen, S.; Connaughton, V.; Grove, J. E.; Chekhtman, A.; Holzworth, R.

    2017-12-01

    The revised Second Fermi GBM TGF catalog includes data on 4144 TGFs detected by the Fermi Gamma-ray Burst Monitor through 2016 July 31. The catalog includes 686 bright TGFs there were detected in orbit and 4135 TGFs that were discovered by ground analysis of GBM data (the two samples overlap). Thirty of the events may have been detected as electrons and positrons rather than gamma-rays: Terrestrial Electron Beams (TEBs). We also provide results from correlating the GBM TGFs with VLF radio detections of the World Wide Lightning Location Network (WWLLN). TGFs with WWLLN associations have their localization uncertainties improved from 800 to 10 km, making it possible to identify specific thunderstorms responsible for the TGFs and opening up new types of scientific investigations. There are 1544 TGFs with WWLLN associations; maps are provided for these and the other TGFs of the catalog. The data tables of the catalog are available for use by the scientific community at the Fermi Science Support Center, at https://fermi.gsfc.nasa.gov/ssc/data/access/gbm/tgf/.

  10. ON THE FERMI -GBM EVENT 0.4 s AFTER GW150914

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, J.; Yu, H.-F. [Max Planck Institute for Extraterrestrial Physics, Giessenbachstrasse, D-85748 Garching (Germany); Burgess, J. M. [Oskar Klein Centre for Cosmoparticle Physics, SE-106 91 Stockholm (Sweden); Savchenko, V., E-mail: jcg@mpe.mpg.de, E-mail: sptfung@mpe.mpg.de, E-mail: jamesb@kth.se, E-mail: savchenk@apc.in2p3.fr [Francois Arago Centre, APC, Université Paris Diderot, CNRS/IN2P3, CEA/Irfu, Observatoire Paris, Sorbonne Paris Cité, 10 rue Alice Domon et Léonie Duquet, F-75205 Paris Cedex 13 (France)

    2016-08-20

    In view of the recent report by Connaughton et al., we analyze continuous time-tagged event (TTE) data of Fermi -gamma-ray burst monitor (GBM) around the time of the gravitational-wave event GW 150914. We find that after proper accounting for low-count statistics, the GBM transient event at 0.4 s after GW 150914 is likely not due to an astrophysical source, but consistent with a background fluctuation, removing the tension between the INTEGRAL /ACS non-detection and GBM. Additionally, reanalysis of other short GRBs shows that without proper statistical modeling the fluence of faint events is over-predicted, as verified for some joint GBM–ACS detections of short GRBs. We detail the statistical procedure to correct these biases. As a result, faint short GRBs, verified by ACS detections, with significances in the broadband light curve even smaller than that of the GBM–GW150914 event are recovered as proper non-zero source, while the GBM–GW150914 event is consistent with zero fluence.

  11. Farewell to GBM-O: Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups.

    Science.gov (United States)

    Hinrichs, Benjamin H; Newman, Scott; Appin, Christina L; Dunn, William; Cooper, Lee; Pauly, Rini; Kowalski, Jeanne; Rossi, Michael R; Brat, Daniel J

    2016-01-13

    Glioblastoma with oligodendroglioma component (GBM-O) was recognized as a histologic pattern of glioblastoma (GBM) by the World Health Organization (WHO) in 2007 and is distinguished by the presence of oligodendroglioma-like differentiation. To better understand the genetic underpinnings of this morphologic entity, we performed a genome-wide, integrated copy number, mutational and transcriptomic analysis of eight (seven primary, primary secondary) cases. Three GBM-O samples had IDH1 (p.R132H) mutations; two of these also demonstrated 1p/19q co-deletion and had a proneural transcriptional profile, a molecular signature characteristic of oligodendroglioma. The additional IDH1 mutant tumor lacked 1p/19q co-deletion, harbored a TP53 mutation, and overall, demonstrated features most consistent with IDH mutant (secondary) GBM. Finally, five tumors were IDH wild-type (IDHwt) and had chromosome seven gains, chromosome 10 losses, and homozygous 9p deletions (CDKN2A), alterations typical of IDHwt (primary) GBM. IDHwt GBM-Os also demonstrated EGFR and PDGFRA amplifications, which correlated with classical and proneural expression subtypes, respectively. Our findings demonstrate that GBM-O is composed of three discrete molecular subgroups with characteristic mutations, copy number alterations and gene expression patterns. Despite displaying areas that morphologically resemble oligodendroglioma, the current results indicate that morphologically defined GBM-O does not correspond to a particular genetic signature, but rather represents a collection of genetically dissimilar entities. Ancillary testing, especially for IDH and 1p/19q, should be used for determining these molecular subtypes.

  12. Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy.

    Science.gov (United States)

    Tong, Luqing; Yi, Li; Liu, Peidong; Abeysekera, Iruni Roshanie; Hai, Long; Li, Tao; Tao, Zhennan; Ma, Haiwen; Xie, Yang; Huang, Yubao; Yu, Shengping; Li, Jiabo; Yuan, Feng; Yang, Xuejun

    2018-07-01

    Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

  13. Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines.

    Science.gov (United States)

    Tezcan, Gulcin; Tunca, Berrin; Bekar, Ahmet; Yalcin, Murat; Sahin, Saliha; Budak, Ferah; Cecener, Gulsah; Egeli, Unal; Demir, Cevdet; Guvenc, Gokcen; Yilmaz, Gozde; Erkan, Leman Gizem; Malyer, Hulusi; Taskapilioglu, Mevlut Ozgur; Evrensel, Turkkan; Bilir, Ayhan

    2015-03-01

    Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.

  14. Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review.

    Science.gov (United States)

    Anjum, Komal; Shagufta, Bibi Ibtesam; Abbas, Syed Qamar; Patel, Seema; Khan, Ishrat; Shah, Sayed Asmat Ali; Akhter, Najeeb; Hassan, Syed Shams Ul

    2017-08-01

    Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. THE FERMI –GBM THREE-YEAR X-RAY BURST CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Jenke, P. A. [CSPAR, SPA University of Alabama in Huntsville, Huntsville, AL 35805 (United States); Linares, M. [Instituto de Astrofísica de Canarias, c/Vía Láctea s/n, E-38205 La Laguna, Tenerife (Spain); Connaughton, V.; Camero-Arranz, A.; Finger, M. H. [Universities Space Research Association, Huntsville, AL 35805 (United States); Beklen, E. [Department of Physics, Suleyman Demirel University, 32260, Isparta (Turkey); Wilson-Hodge, C. A. [Marshall Space Flight Center, Huntsville, AL 35812 (United States)

    2016-08-01

    The Fermi Gamma-ray Burst Monitor (GBM) is an all-sky gamma-ray monitor well known in the gamma-ray burst (GRB) community. Although GBM excels in detecting the hard, bright extragalactic GRBs, its sensitivity above 8 keV and its all-sky view make it an excellent instrument for the detection of rare, short-lived Galactic transients. In 2010 March, we initiated a systematic search for transients using GBM data. We conclude this phase of the search by presenting a three-year catalog of 1084 X-ray bursts. Using spectral analysis, location, and spatial distributions we classified the 1084 events into 752 thermonuclear X-ray bursts, 267 transient events from accretion flares and X-ray pulses, and 65 untriggered gamma-ray bursts. All thermonuclear bursts have peak blackbody temperatures broadly consistent with photospheric radius expansion (PRE) bursts. We find an average rate of 1.4 PRE bursts per day, integrated over all Galactic bursters within about 10 kpc. These include 33 and 10 bursts from the ultra-compact X-ray binaries 4U 0614+09 and 2S 0918-549, respectively. We discuss these recurrence times and estimate the total mass ejected by PRE bursts in our Galaxy.

  16. Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy

    NARCIS (Netherlands)

    Kriz, Wilhelm; Loewen, Jana; Federico, Giuseppina; van den Born, Jacob; Groene, Elisabeth; Groene, Hermann Josef

    2017-01-01

    Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN), generally considered to emerge from different sites of overproduction: GBM components from podocytes and mesangial matrix from mesangial cells. Reevaluation of 918

  17. Correlative Spectral Analysis of Gamma-Ray Bursts using Swift-BAT and GLAST-GBM

    International Nuclear Information System (INIS)

    Stamatikos, Michael; Sakamoto, Taka; Band, David L.

    2008-01-01

    We discuss the preliminary results of spectral analysis simulations involving anticipated correlated multi-wavelength observations of gamma-ray bursts (GRBs) using Swift's Burst Alert Telescope (BAT) and the Gamma-Ray Large Area Space Telescope's (GLAST) Burst Monitor (GLAST-GBM), resulting in joint spectral fits, including characteristic photon energy (E peak ) values, for a conservative annual estimate of ∼30 GRBs. The addition of BAT's spectral response will (i) complement in-orbit calibration efforts of GBM's detector response matrices, (ii) augment GLAST's low energy sensitivity by increasing the ∼20-100 keV effective area, (iii) facilitate ground-based follow-up efforts of GLAST GRBs by increasing GBM's source localization precision, and (iv) help identify a subset of non-triggered GRBs discovered via off-line GBM data analysis. Such multi-wavelength correlative analyses, which have been demonstrated by successful joint-spectral fits of Swift-BAT GRBs with other higher energy detectors such as Konus-WIND and Suzaku-WAM, would enable the study of broad-band spectral and temporal evolution of prompt GRB emission over three energy decades, thus potentially increasing science return without placing additional demands upon mission resources throughout their contemporaneous orbital tenure over the next decade.

  18. Correlative Spectral Analysis of Gamma-Ray Bursts using Swift-BAT and GLAST-GBM

    International Nuclear Information System (INIS)

    Stamatikos, Michael; Sakamoto, Takanori; Band, David L.

    2008-01-01

    We discuss the preliminary results of spectral analysis simulations involving anticipated correlated multi-wavelength observations of gamma-ray bursts (GRBs) using Swift's Burst Alert Telescope (BAT) and the Gamma-Ray Large Area Space Telescope's (GLAST) Burst Monitor (GLAST-GBM), resulting in joint spectral fits, including characteristic photon energy (E peak ) values, for a conservative annual estimate of ∼30 GRBs. The addition of BAT/s spectral response will (i) complement in-orbit calibration efforts of GBM's detector response matrices, (ii) augment GLAST's low energy sensitivity by increasing the ∼20-100 keV effective area, (iii) facilitate ground-based follow-up efforts of GLAST GRBs by increasing GBM's source localization precision, and (iv) help identify a subset of non-triggered GRBs discovered via off-line GBM data analysis. Such multi-wavelength correlative analyses, which have been demonstrated by successful joint-spectral fits of Swift-BAT GRBs with other higher energy detectors such as Konus-WIND and Suzaku-WAM, would enable the study of broad-band spectral and temporal evolution of prompt GRB emission over three energy decades, thus potentially increasing science return without placing additional demands upon mission resources throughout their contemporaneous orbital tenure over the next decade

  19. Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.

    Science.gov (United States)

    Lee, Sang Y; Zhu, Junjia; Salzberg, Anna C; Zhang, Bo; Liu, Dajiang J; Muscat, Joshua E; Langan, Sara T; Connor, James R

    2017-01-01

    Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119-0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.

  20. Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.

    Directory of Open Access Journals (Sweden)

    Sang Y Lee

    Full Text Available Human hemochromatosis protein (HFE is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM. However, the effect of other single nucleotide variation (SNV in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA GBM (Caucasian only database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI: 0.2119-0.3223 or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159 HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.

  1. VizieR Online Data Catalog: Short GRBs with Fermi GBM and Swift BAT (Burns+, 2016)

    Science.gov (United States)

    Burns, E.; Connaughton, V.; Zhang, B.-B.; Lien, A.; Briggs, M. S.; Goldstein, A.; Pelassa, V.; Troja, E.

    2018-01-01

    Compact binary system mergers are expected to generate gravitational radiation detectable by ground-based interferometers. A subset of these, the merger of a neutron star with another neutron star or a black hole, are also the most popular model for the production of short gamma-ray bursts (GRBs). The Swift Burst Alert Telescope (BAT) and the Fermi Gamma-ray Burst Monitor (GBM) trigger on short GRBs (SGRBs) at rates that reflect their relative sky exposures, with the BAT detecting 10 per year compared to about 45 for GBM. We examine the SGRB populations detected by Swift BAT and Fermi GBM. (4 data files).

  2. The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review.

    Science.gov (United States)

    Monticelli, M; Zeppa, P; Zenga, F; Altieri, R; Mammi, M; Bertero, L; Castellano, I; Cassoni, P; Melcarne, A; La Rocca, G; Sabatino, G; Ducati, A; Garbossa, D

    2018-07-01

    Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies. We have also analyzed the cellular biology and the interactions between GBM and the surrounding environment. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells

    Directory of Open Access Journals (Sweden)

    Tzuu-Yuan Huang

    2012-01-01

    Full Text Available Demethoxycurcumin (DMC; a curcumin-related demethoxy compound has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC50 values at 22.71 μM and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP, DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

  4. Fermi GBM Observations During the Second Observing Run of LIGO/Virgo

    Science.gov (United States)

    Goldstein, Adam; Fermi-GBM

    2018-01-01

    The Fermi Gamma-ray Burst Monitor (GBM) is a prolific detector of gamma-ray bursts (GRBs) and detects more short duration GRBs than any other instrument currently in operation. Short GRBs are thought to be associated with the mergers of binary neutron star systems (or neutron star-black hole systems), and are therefore considered likely counterparts to gravitational-wave detections from LIGO/Virgo. We report on the GBM observations during the second observing run of LIGO/Virgo and detail the physical and astrophysical insights that might be gleaned from a joint detection of a short GRB and a gravitational-wave source.

  5. The InterPlanetary Network Supplement to the Second Fermi GBM Catalog of Cosmic Gamma-Ray Bursts

    Energy Technology Data Exchange (ETDEWEB)

    Hurley, K. [University of California, Berkeley, Space Sciences Laboratory, 7 Gauss Way, Berkeley, CA 94720-7450 (United States); Aptekar, R. L.; Golenetskii, S. V.; Frederiks, D. D.; Svinkin, D. S. [Ioffe Institute, Politekhnicheskaya 26, St. Petersburg 194021 (Russian Federation); Pal’shin, V. D. [Vedeneeva 2-31, St. Petersburg (Russian Federation); Briggs, M. S.; Meegan, C. [University of Alabama in Huntsville, NSSTC, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Connaughton, V. [Universities Space Research Association, NSSTC, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Goldsten, J. [Applied Physics Laboratory, Johns Hopkins University, Laurel, MD 20723 (United States); Boynton, W.; Fellows, C.; Harshman, K. [University of Arizona, Department of Planetary Sciences, Tucson, Arizona 85721 (United States); Mitrofanov, I. G.; Golovin, D. V.; Kozyrev, A. S.; Litvak, M. L.; Sanin, A. B. [Space Research Institute, 84/32, Profsoyuznaya, Moscow 117997 (Russian Federation); Rau, A.; Kienlin, A. von, E-mail: khurley@ssl.berkeley.edu [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse, Postfach 1312, Garching, D-85748 (Germany); and others

    2017-04-01

    InterPlanetary Network (IPN) data are presented for the gamma-ray bursts in the second Fermi Gamma-Ray Burst Monitor (GBM) catalog. Of the 462 bursts in that catalog between 2010 July 12 and 2012 July 11, 428, or 93%, were observed by at least 1 other instrument in the 9-spacecraft IPN. Of the 428, the localizations of 165 could be improved by triangulation. For these bursts, triangulation gives one or more annuli whose half-widths vary between about 2.′3° and 16°, depending on the peak flux, fluence, time history, arrival direction, and the distance between the spacecraft. We compare the IPN localizations with the GBM 1 σ , 2 σ , and 3 σ error contours and find good agreement between them. The IPN 3 σ error boxes have areas between about 8 square arcminutes and 380 square degrees, and are an average of 2500 times smaller than the corresponding GBM 3 σ localizations. We identify four bursts in the IPN/GBM sample whose origins were given as “uncertain,” but may in fact be cosmic. This leads to an estimate of over 99% completeness for the GBM catalog.

  6. Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor

    Directory of Open Access Journals (Sweden)

    Adam Autry

    2017-12-01

    Full Text Available BACKGROUND: Although the contrast-enhancing (CE lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM, there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh− challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh− and CE GBM (Enh+ samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Methods: Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. Results: The Enh+ and Enh− tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. CONCLUSIONS: The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh− tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM.

  7. Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

    Science.gov (United States)

    Autry, Adam; Phillips, Joanna J; Maleschlijski, Stojan; Roy, Ritu; Molinaro, Annette M; Chang, Susan M; Cha, Soonmee; Lupo, Janine M; Nelson, Sarah J

    2017-12-01

    Although the contrast-enhancing (CE) lesion on T 1 -weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T 2 -weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. The Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. CXCR4 expression varies significantly among different subtypes of glioblastoma multiforme (GBM) and its low expression or hypermethylation might predict favorable overall survival.

    Science.gov (United States)

    Ma, Xinlong; Shang, Feng; Zhu, Weidong; Lin, Qingtang

    2017-09-01

    CXCR4 is an oncogene in glioblastoma multiforme (GBM) but the mechanism of its dysregulation and its prognostic value in GBM have not been fully understood. Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on data from GSE16011 in GEO datasets and in GBM cohort in TCGA database (TCGA-GBM). Kaplan Meier curves of overall survival (OS) were generated to assess the association between CXCR4 expression/methylation and OS in patients with GBM. GBM patients with high CXCR4 expression had significantly worse 5 and 10 yrs OS (p GBM subtypes, there was an inverse relationship between overall DNA methylation and CXCR4 expression. CXCR4 expression was significantly lower in CpG island methylation phenotype (CIMP) group than in non CIMP group. Log rank test results showed that patients with high CXCR4 methylation (first tertile) had significantly better 5 yrs OS (p = 0.038). CXCR4 expression is regulated by DNA methylation in GBM and its low expression or hypermethylation might indicate favorable OS in GBM patients.

  9. miR-139-5p suppresses cancer cell migration and invasion through targeting ZEB1 and ZEB2 in GBM.

    Science.gov (United States)

    Yue, Sihai; Wang, Lihua; Zhang, Hui; Min, Youhui; Lou, Yongli; Sun, Hongshan; Jiang, Yu; Zhang, Wenjin; Liang, Aming; Guo, Yongkun; Chen, Ping; Lv, Guowei; Wang, Liuxiang; Zong, Qinghua; Li, Yong

    2015-09-01

    Invasion and migration of glioblastoma multiforme (GBM) is a multistep process and an important phenotype that causes this disease to invade surrounding tissues in the brain. Recent studies have highlighted that miRNAs play a pivotal role in controlling GBM cell plasticity. In this report, we used wound healing and transwell assays to identify a novel role of miR-139-5p in inhibition of GBM cell migration and invasion. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-139-5p inhibited expression of ZEB1 and ZEB2, which are master regulators of tumor metastasis. MiR-139-5p specifically interacts with the 3'-UTR regions of ZEB1 and ZEB2, attenuating their expression in GBM cells. To corroborate this finding, we rescued ZEB1 and ZEB2 expression and found partial but significant increases in miR-139-5p-suppressed invasion of GBM cells. The biological relevance of our study was validated by analyzing levels of miR-139-5p in GBM tissue. We found that its expression significantly downregulated compared to normal tissue and shorter overall survival rates in patients with lower miR-139-5p expression. These results confirm that miR-139-5p suppresses GBM migration and invasion and highlight its potential as a biomarker and therapeutic target for treating GBM.

  10. SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.

    Science.gov (United States)

    Zhang, Jing; Jiang, Huawei; Shao, Jiaofang; Mao, Ruifang; Liu, Jie; Ma, Yingying; Fang, Xuefeng; Zhao, Na; Zheng, Shu; Lin, Biaoyang

    2014-11-01

    SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM. Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells. High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways. Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

  11. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  12. The Successful Synergy of Swift and Fermi/GBM in Magnetars

    Science.gov (United States)

    Kouveliotou, Chryssa

    2011-01-01

    The magnetar rate of discovery has increased dramatically in the last decade. Five sources were discovered in the last three years alone as a result of the very efficient synergy among three X- and .gamma-ray instruments on NASA satellites: the Swift/Burst Alert Telescope (BAT), the Fermi/Gamma ray Burst Monitor (GBM), and the Rossi X-Ray Timing Explorer; RXTE/Proportional Counter Array (PCA). To date, there are approx. 25 magnetar candidates, of which two are (one each) in the Large and Small Magellanic Cloud and the rest reside on the Galactic plane of our Milky Way. I will discuss here the main properties of the Magnetar Population and the common projects that can be achieved with the synergy of Swift and GBM.

  13. Tamoxifen in combination with temozolomide induce a synergistic inhibition of PKC-pan in GBM cell lines.

    Science.gov (United States)

    Balça-Silva, Joana; Matias, Diana; do Carmo, Anália; Girão, Henrique; Moura-Neto, Vivaldo; Sarmento-Ribeiro, Ana Bela; Lopes, Maria Celeste

    2015-04-01

    Glioblastoma (GBM) is a highly proliferative, angiogenic grade IV astrocytoma that develops resistance to the alkylating agents used in chemotherapy, such as temozolomide (TMZ), which is considered the gold standard. The mean survival time for GBM patients is approximately 12 months, increasing to 14.6 months after TMZ treatment. The resistance of GBM to chemotherapy seems to be associated to genetic alterations and to the constitutive activation of several signaling pathways. Therefore, the combination of different drugs with different mechanisms of action may contribute to circumvent the chemoresistance of glioma cells. Here we describe the potential synergistic behavior of the therapeutic combination of tamoxifen (TMX), a known inhibitor of PKC, and TMZ in GBM. We used two GBM cell lines incubated in absence and presence of TMX and/or TMZ and measured cell viability, proliferation, apoptosis, cell cycle, migration ability, cytoskeletal organization and the phosphorylated amount of the p-PKC-pan. The combination of low doses of TMX with increasing doses of TMZ shows an increased antiproliferative and apoptotic effect compared to the effect with TMX alone. The combination of TMX and TMZ seems to potentiate the effect of each other. These alterations seem to be associated to a decrease in the phosphorylation status of PKC. We emphasize that TMX is an inhibitor of the p-PKC-pan and that these combination is more effective in the reduction of proliferation and in the increase of apoptosis than each drug alone, which presents a new therapeutic strategy in GBM treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel.

    Science.gov (United States)

    Grossman, Rachel; Burger, Peter; Soudry, Ethan; Tyler, Betty; Chaichana, Kaisorn L; Weingart, Jon; Olivi, Alessandro; Gallia, Gary L; Sidransky, David; Quiñones-Hinojosa, Alfredo; Ye, Xiaobu; Brem, Henry

    2015-12-01

    We examined the relationship between the O(6)-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p=0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p=0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p=0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis.

    Science.gov (United States)

    Fu, Yuyang; Du, Yong; Mohan, Chandra

    2007-08-01

    Lupus nephritis is an immune-mediated disease, where antibodies and T cells both play pathogenic roles. Since spontaneous lupus nephritis in mouse models takes 6-12 months to manifest, there is an urgent need for a mouse model that can be used to delineate the pathogenic processes that lead to immune nephritis, over a quicker time frame. We propose that the experimental anti-glomerular basement membrane (GBM) disease model might be a suitable tool for uncovering some of the molecular steps underlying lupus nephritis. This article reviews the current evidence that supports the use of the experimental anti-GBM nephritis model for studying spontaneous lupus nephritis. Importantly, out of about 25 different molecules that have been specifically examined in the experimental anti-GBM model and also spontaneous lupus nephritis, all influence both diseases concordantly, suggesting that the experimental model might be a useful tool for unraveling the molecular basis of spontaneous lupus nephritis. This has important clinical implications, both from the perspective of genetic susceptibility as well as clinical therapeutics.

  16. Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.

    Science.gov (United States)

    Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei

    2013-11-01

    The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

  17. Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

    Science.gov (United States)

    Ge, Haitao; Mu, Luyan; Jin, Linchun; Yang, Changlin; Chang, Yifan Emily; Long, Yu; DeLeon, Gabriel; Deleyrolle, Loic; Mitchell, Duane A; Kubilis, Paul S; Lu, Dunyue; Qi, Jiping; Gu, Yunhe; Lin, Zhiguo; Huang, Jianping

    2017-10-01

    Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM. © 2017 UICC.

  18. TU-AB-BRA-11: Evaluation of Fully Automatic Volumetric GBM Segmentation in the TCGA-GBM Dataset: Prognosis and Correlation with VASARI Features

    International Nuclear Information System (INIS)

    Rios Velazquez, E; Meier, R; Dunn, W; Gutman, D; Alexander, B; Wiest, R; Reyes, M; Bauer, S; Aerts, H

    2015-01-01

    Purpose: Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. Methods: MRI sets of 67 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA), including necrosis, edema, contrast enhancing and non-enhancing tumor. Spearman’s correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Results: Auto-segmented sub-volumes showed high agreement with manually delineated volumes (range (r): 0.65 – 0.91). Also showed higher correlation with VASARI features (auto r = 0.35, 0.60 and 0.59; manual r = 0.29, 0.50, 0.43, for contrast-enhancing, necrosis and edema, respectively). The contrast-enhancing volume and post-contrast abnormal volume showed the highest C-index (0.73 and 0.72), comparable to manually defined volumes (p = 0.22 and p = 0.07, respectively). The non-enhancing region defined by BraTumIA showed a significantly higher prognostic value (CI = 0.71) than the edema (CI = 0.60), both of which could not be distinguished by manual delineation. Conclusion: BraTumIA tumor sub-compartments showed higher correlation with VASARI data, and equivalent performance in terms of prognosis compared to manual sub-volumes. This method can enable more reproducible definition and quantification of imaging based biomarkers and has a large potential in high-throughput medical imaging research

  19. TU-AB-BRA-11: Evaluation of Fully Automatic Volumetric GBM Segmentation in the TCGA-GBM Dataset: Prognosis and Correlation with VASARI Features

    Energy Technology Data Exchange (ETDEWEB)

    Rios Velazquez, E [Dana-Farber Cancer Institute | Harvard Medical School, Boston, MA (United States); Meier, R [Institute for Surgical Technology and Biomechanics, Bern, NA (Switzerland); Dunn, W; Gutman, D [Emory University School of Medicine, Atlanta, GA (United States); Alexander, B [Dana- Farber Cancer Institute, Brigham and Womens Hospital, Harvard Medic, Boston, MA (United States); Wiest, R; Reyes, M [Institute for Surgical Technology and Biomechanics, University of Bern, Bern, NA (Switzerland); Bauer, S [Institute for Surgical Technology and Biomechanics, Support Center for Adva, Bern, NA (Switzerland); Aerts, H [Dana-Farber/Brigham Womens Cancer Center, Boston, MA (United States)

    2015-06-15

    Purpose: Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. Methods: MRI sets of 67 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA), including necrosis, edema, contrast enhancing and non-enhancing tumor. Spearman’s correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Results: Auto-segmented sub-volumes showed high agreement with manually delineated volumes (range (r): 0.65 – 0.91). Also showed higher correlation with VASARI features (auto r = 0.35, 0.60 and 0.59; manual r = 0.29, 0.50, 0.43, for contrast-enhancing, necrosis and edema, respectively). The contrast-enhancing volume and post-contrast abnormal volume showed the highest C-index (0.73 and 0.72), comparable to manually defined volumes (p = 0.22 and p = 0.07, respectively). The non-enhancing region defined by BraTumIA showed a significantly higher prognostic value (CI = 0.71) than the edema (CI = 0.60), both of which could not be distinguished by manual delineation. Conclusion: BraTumIA tumor sub-compartments showed higher correlation with VASARI data, and equivalent performance in terms of prognosis compared to manual sub-volumes. This method can enable more reproducible definition and quantification of imaging based biomarkers and has a large potential in high-throughput medical imaging research.

  20. Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.

    Science.gov (United States)

    Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

    2015-01-21

    Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.

  1. Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and growth of GBM.

    Science.gov (United States)

    Yang, Ji-Peng; Yang, Jian-Kai; Li, Chen; Cui, Zhi-Qiang; Liu, Hong-Jiang; Sun, Xiao-Feng; Geng, Shao-Mei; Lu, Sheng-Kui; Song, Jian; Guo, Cheng-Yong; Jiao, Bao-Hua

    2017-12-16

    ZMYND11 (zinc finger MYND-type containing 11) has been widely regarded to be involved in a variety of cancers as a potential suppressor. However, the biological role and mechanism of ZMYND11 in glioblastoma multiform (GBM) remain unknown. In this study, we found that ZMYND11 expression was remarkably decreased in GBM tissues from 20 cases and cell line (U87) compared to normal brain tissue from 10 cases (P GBM tissue and U87 cells by changing the expression level of miR-196a-5p with lentivirus and plasmid vector. Furthermore, we demonstrated that decreased ZMYND11 could reverse suppressive effect of downregulated miR-196a-5p on U87 by rescue experiment. Taken together, ZMYND11 was demonstrated to be a potential and extremely promising suppressor of GBM, while miRNA-196a-5p was quite an important target of treatment of GBM. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Selective anti-tumor activity of the novel fluoropyrimidine polymer F10 towards G48a orthotopic GBM tumors.

    Science.gov (United States)

    Gmeiner, William H; Lema-Tome, Carla; Gibo, Denise; Jennings-Gee, Jamie; Milligan, Carol; Debinski, Waldemar

    2014-02-01

    F10 is a novel anti-tumor agent with minimal systemic toxicity in vivo and which displays strong cytotoxicity towards glioblastoma (GBM) cells in vitro. Here we investigate the cytotoxicity of F10 towards GBM cells and evaluate the anti-tumor activity of locally-administered F10 towards an orthotopic xenograft model of GBM. The effects of F10 on thymidylate synthase (TS) inhibition and Topoisomerase 1 (Top1) cleavage complex formation were evaluated using TS activity assays and in vivo complex of enzyme bioassays. Cytotoxicity of F10 towards normal brain was evaluated using cortices from embryonic (day 18) mice. F10 displays minimal penetrance of the blood-brain barrier and was delivered by intra-cerebral (i.c.) administration and prospective anti-tumor response towards luciferase-expressing G48a human GBM tumors in nude mice was evaluated using IVIS imaging. Histological examination of tumor and normal brain tissue was used to assess the selectivity of anti-tumor activity. F10 is cytotoxic towards G48a, SNB-19, and U-251 MG GBM cells through dual targeting of TS and Top1. F10 is not toxic to murine primary neuronal cultures. F10 is well-tolerated upon i.c. administration and induces significant regression of G48a tumors that is dose-dependent. Histological analysis from F10-treated mice revealed tumors were essentially completely eradicated in F10-treated mice while vehicle-treated mice displayed substantial infiltration into normal tissue. F10 displays strong efficacy for GBM treatment with minimal toxicity upon i.c. administration establishing F10 as a promising drug-candidate for treating GBM in human patients.

  3. Differential role of EGF and BFGF in human GBM-TIC proliferation: relationship to EGFR-tyrosine kinase inhibitor sensibility.

    Science.gov (United States)

    Bajetto, A; Porcile, C; Pattarozzi, A; Scotti, L; Aceto, A; Daga, A; Barbieri, F; Florio, T

    2013-01-01

    Glioblastoma multiforme (GBM) is among the most devastating human tumors being rapidly fatal despite aggressive surgery, radiation and chemotherapies. It is characterized by extensive dissemination of tumor cells within the brain that hinders complete surgical resection. GBM tumor initiating-cells (TICs) are a rare subpopulation of cells responsible for tumor development, growth, invasiveness and recurrence after chemotherapy. TICs from human GBM can be selected in vitro using the same conditions permissive for the growth of normal neural cells, of which share some features including marker expression, self-renewal capacity, long-term proliferation, and ability to differentiate into neuronal and glial cells. EGFR overexpression and its constitutive activation is one of the most important signaling alteration identified in GBM, and its pharmacological targeting represents an attractive therapeutic goal. We previously demonstrated that human GBM TICs have different sensitivity to the EGFR kinase inhibitors erlotinib and gefitinib, depending on the differential modulation of downstream signaling cascades. In this work we investigated the mechanisms of resistance to erlotinib in two human GBM TIC cultures, analyzing EGF and bFGF individual contribution to proliferation, clonogenicity, and migration. We demonstrated the presence of a small cell subpopulation whose proliferation is supported by EGF and a larger one mainly dependent on bFGF. Thus, insensitivity to EGFR kinase inhibitors as far as TIC proliferation results from a predominant FGFR activation that hides the inhibitory effects induced on EGFR signaling. Conversely, EGF and bFGF induced cell migration with similar efficacy. In addition, unlike neural stem/progenitors cells, the removal of chondroitin sulphate proteoglycans from cell surface was unable to discern EGF- and bFGF-dependent subpopulations in GBM TICs.

  4. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

    International Nuclear Information System (INIS)

    Monticone, Massimiliano; Giaretti, Walter; Pfeffer, Ulrich; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi

    2012-01-01

    Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting. We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting. Massimiliano Monticone and Antonio Daga contributed equally to this work

  5. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells.

    Science.gov (United States)

    Monticone, Massimiliano; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi; Giaretti, Walter; Pfeffer, Ulrich; Castagnola, Patrizio

    2012-08-17

    Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.Massimiliano Monticone and Antonio Daga contributed equally to this work.

  6. IMPLICATIONS OF THE TENTATIVE ASSOCIATION BETWEEN GW150914 AND A FERMI -GBM TRANSIENT

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang; Yuan, Qiang; Jin, Zhi-Ping; Fan, Yi-Zhong; Liu, Si-Ming; Wei, Da-Ming [Key Laboratory of dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Science, Nanjing 210008 (China); Zhang, Fu-Wen, E-mail: yzfan@pmo.ac.cn, E-mail: dmwei@pmo.ac.cn, E-mail: fwzhang@glut.edu.cn [College of Science, Guilin University of Technology, Guilin 541004 (China)

    2016-08-10

    The merger-driven gamma-ray bursts (GRBs) and their associated gravitational-wave (GW) radiation, if both are successfully detected, have some far-reaching implications, including, for instance: (i) the statistical comparison of the physical properties of the short/long-short GRBs with and without GW detection can test the general origin model; (ii) revealing the physical processes taking place at the central engine; (iii) measuring the velocity of the gravitational wave directly/accurately. In this work, we discuss these implications in the case of a possible association of GW150914/Gamma-ray Burst Monitor (GBM) transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event may be a distinct outlier in some statistical diagrams, possibly due to its specific binary black hole merger origin. However, the presence of a “new” group of SGRBs with “unusual” physical parameters is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, the magnetic activity rather than the neutrino process is likely responsible for the energy extraction, and the accretion disk mass is estimated to be ∼10{sup −5} M {sub ⊙}. The GW150914/GBM transient 150914 association, if confirmed, would provide the first opportunity to directly measure the GW velocity, and its departure from the speed of the light should be within a factor of ∼10{sup −17}.

  7. Immunoadsorption in Anti-GBM Glomerulonephritis: Case Report in a Child and Literature Review.

    Science.gov (United States)

    Dorval, Guillaume; Lion, Mathilde; Guérin, Sophie; Krid, Saoussen; Galmiche-Rolland, Louise; Salomon, Rémi; Boyer, Olivia

    2017-11-01

    Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare autoimmune disease that is characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage. Anti-GBM GN is caused by autoantibodies (classically type G immunoglobulin) directed against the α3 subunit of type IV collagen. Without any appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. Immunoadsorption (IA) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. IA has seldom been used in adult patients with good tolerance and efficiency. We report herein the first pediatric case successfully treated with IA combined with immunosuppressive drugs in a 7-year-old girl who presented acute kidney injury (estimated glomerular filtration rate 38 mL/minute/1.73 m 2 ). A kidney biopsy revealed numerous >80% glomerular crescents and linear IgG deposits along the glomerular basement membrane. Ten IA sessions led to rapid and sustained clearance of autoantibodies and improvement of kidney function until 21 months after onset (glomerular filtration rate 87 mL/minute/1.73 m 2 ). No adverse effect was noted. This report adds to the growing body of evidence suggesting IA as a therapeutic alternative to plasma exchanges in anti-GBM GN. The other 27 published pediatric cases of anti-GBM GN are reviewed. Copyright © 2017 by the American Academy of Pediatrics.

  8. Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM).

    Science.gov (United States)

    Demeure, Kevin; Fack, Fred; Duriez, Elodie; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Bougnaud, Sébastien; Bjerkvig, Rolf; Domon, Bruno; Niclou, Simone P

    2016-02-01

    Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future

  9. Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM).

    Science.gov (United States)

    Brehmer, Stefanie; Grimm, Mario Alexander; Förster, Alex; Seiz-Rosenhagen, Marcel; Welzel, Grit; Stieler, Florian; Wenz, Frederik; Groden, Christoph; Mai, Sabine; Hänggi, Daniel; Giordano, Frank Anton

    2018-04-24

    Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

  10. Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort.

    Science.gov (United States)

    Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

    2015-05-01

    Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic

  11. Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression.

    Science.gov (United States)

    Tezcan, Gulcin; Tunca, Berrin; Bekar, Ahmet; Budak, Ferah; Sahin, Saliha; Cecener, Gulsah; Egeli, Unal; Taskapılıoglu, Mevlut Ozgur; Kocaeli, Hasan; Tolunay, Sahsine; Malyer, Hulusi; Demir, Cevdet; Tumen, Gulendam

    2014-01-01

    The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.

  12. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

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    Monticone Massimiliano

    2012-08-01

    Full Text Available Abstract Background Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting. We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type or highly diffuse single tumor cell infiltration (HD-type. Methods We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM. Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Results Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. Conclusions This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting. Massimiliano Monticone and Antonio Daga contributed equally to this work

  13. Fermi GBM Observations of Terrestrial Gamma-Ray Flashes

    Science.gov (United States)

    Wilson-Hodge, Colleen A.; Briggs, M. S.; Connaughton, V.; Fishman, G. J.; Bhat, P. N.; Paciesas, W. S.; Preece, R.; Kippen, R. M.; vonKienlin, A.; Dwyer, J. R.; hide

    2010-01-01

    This slide presentation explores the relationship between Terrestrial Gamma-Ray Flashes (TGF) and lightning. Using data from the World-Wide Lightning Location Network (WWLLN), and the gamma ray observations from Fermi's Gamma-ray Burst Monitor (GBM), the study reviews any causal relationship between TGFs and lightning. The conclusion of the study is that the TGF and lightning are simultaneous with out a causal relationship.

  14. Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

    Science.gov (United States)

    Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

    2017-08-01

    The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

  15. SOCS3 promoter hypermethylation is a favorable prognosticator and a novel indicator for G-CIMP-positive GBM patients.

    Science.gov (United States)

    Feng, Ying; Wang, Zheng; Bao, Zhaoshi; Yan, Wei; You, Gan; Wang, Yinyan; Hu, Huimin; Zhang, Wei; Zhang, Quangeng; Jiang, Tao

    2014-01-01

    Hypermethylation of the suppressor of cytokine signaling 3(SOCS3) promoter has been reported to predict a poor prognosis in several cancers including glioblastoma multiforme (GBM). We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP), when a large number of gene loci are simultaneously hypermethylated. A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months) and 20 short-term survivors (STS; overall survival ≤ 9 months). The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status. Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA) and the Chinese Cancer Genome Atlas(CGGA). In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients. Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.

  16. SOCS3 promoter hypermethylation is a favorable prognosticator and a novel indicator for G-CIMP-positive GBM patients.

    Directory of Open Access Journals (Sweden)

    Ying Feng

    Full Text Available Hypermethylation of the suppressor of cytokine signaling 3(SOCS3 promoter has been reported to predict a poor prognosis in several cancers including glioblastoma multiforme (GBM. We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP, when a large number of gene loci are simultaneously hypermethylated.A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months and 20 short-term survivors (STS; overall survival ≤ 9 months. The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status.Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA and the Chinese Cancer Genome Atlas(CGGA. In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients.Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.

  17. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-GBM autoantibodies specific for α345NC1 hexamers

    Science.gov (United States)

    Olaru, Florina; Wang, Xu-Ping; Luo, Wentian; Ge, Linna; Miner, Jeffrey H; Kleinau, Sandra; Geiger, Xochiquetzal J.; Wasiluk, Andrew; Heidet, Laurence; Kitching, A. Richard; Borza, Dorin-Bogdan

    2012-01-01

    Goodpasture disease is an autoimmune kidney disease mediated by autoAbs against NC1 monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis. We identified a novel type of human IgG4-restricted anti-GBM autoAbs associated with mild non-progressive glomerulonephritis, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these anti-GBM autoAbs were investigated in mouse models recapitulating this phenotype. Wild type and FcγRIIB−/− mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoAbs specific for α345NC1 hexamers, which bound to the GBM in vivo but did not cause glomerulonephritis. In these mice, intact collagen IV from murine GBM was not immunogenic. However, in Col4a3−/− Alport mice, both intact collagen IV and NC1 hexamers from murine GBM elicited IgG antibodies specific for α3α4α5NC1 hexamers, which were not subclass restricted. As heterologous antigen in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a and IgG2b autoAbs specific for α345NC1 hexamers and induced anti-GBM Ab glomerulonephritis. These findings indicate that tolerance toward autologous intact α3α4α5(IV) collagen is established in hosts expressing this antigen, even though autoreactive B cells specific for α345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic α3α4α5NC1 hexamers. This provides a mechanism eliciting autoAbs specific for α345NC1 hexamers, which are restricted to non-inflammatory IgG subclasses and non-nephritogenic. In Alport syndrome, lack of tolerance toward α3α4α5(IV) collagen promotes production of alloantibodies to α345NC1 hexamers, including pro-inflammatory IgG subclasses which mediate post-transplant anti-GBM nephritis. PMID:23303673

  18. VizieR Online Data Catalog: The Fermi-GBM three-year X-ray burst catalog (Jenke+, 2016)

    Science.gov (United States)

    Jenke, P. A.; Linares, M.; Connaughton, V.; Beklen, E.; Camero-Arranz, A.; Finger, M. H.; Wilson-Hodge, C. A.

    2018-03-01

    Gamma-ray Burst Monitor (GBM) is an all-sky monitor whose primary objective is to extend the energy range over which gamma-ray bursts are observed in the Large Area Telescope on Fermi (Meegan et al. 2009ApJ...702..791M). GBM consists of 12 NaI detectors with a diameter of 12.7 cm and a thickness of 1.27 cm and two bismuth germanate (BGO) detectors with a diameter and thickness of 12.7 cm. GBM has three continuous data types: CTIME data with nominal 0.256 s time resolution and 8-channel spectral resolution used for event detection and localization, CSPEC data with nominal 4.096 s time resolution and 128-channel spectral resolution, which are used for spectral modeling, and CTTE (continuous-time tagged event) data with time stamps (2 μs precision) on individual events at full 128-channel spectral resolution, which were made available in 2012 November. The Fermi-GBM X-ray Burst Monitor relies on daily inspection of CTIME channel 1 (12-25 keV) data and began operations on 2010 March 12. (3 data files).

  19. Overview of Green Building Material (GBM Policies and Guidelines with Relevance to Indoor Air Quality Management in Taiwan

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    Wen-Tien Tsai

    2017-12-01

    Full Text Available The objective of this paper was to offer a preliminary overview of Taiwan’s success in green building material (GBM efforts through legal systems and promotion measures, which are relevant to the contribution to indoor air quality (IAQ due to sustainability and health issues. In the first part of the paper, the IAQ regulations are summarized to highlight the second nation (i.e., Taiwan around the world in IAQ management by the law. In addition, the permissible exposure limits (PEL in Taiwan for airborne hazardous substances were first promulgated in 1974 to deal with occupational health issues in the workplace environment. In the second part of the paper, the developing status of the GBM in Taiwan is analyzed to unravel its connection with the Indoor Air Quality Management Act (IAQMA, promulgated on 23 November 2011. By the end of September 2017, a total of 645 GBM labels have been conferred, covering over 5000 green products. Due to the effectiveness of source control, the healthy GBM occupies most of the market, accounting for about 75%. The IAQMA, which took force in November 2012, is expected to significantly increase the use of healthy GBM in new building construction and remodeling, especially in low formaldehyde (HCHO/volatile organic compound (VOC-emitting products.

  20. Fermi GBM: Highlights from the First Year

    Science.gov (United States)

    Wilson-Hodge, Colleen A.

    2009-01-01

    The Fermi Gamma ray Burst Monitor is an all-sky instrument sensitive to photons from about 8 keV to 40 MeV. I will summarize highlights from the first year, including triggered observations of gamma ray bursts, soft gamma ray repeaters, and terrestrial gamma flashes, and observations in the continuous data of X-ray binaries and accreting X-ray pulsars. GBM provides complementary observations to Swift/BAT, observing many of the same sources, but over a wider energy range.

  1. Anti-glomerular basement membrane (anti-GBM) disease accompanied by vasculitis that was not positive for antineutrophil cytoplasmic antibodies to myeloperoxidase and proteinase 3: a report of two cases and the incidence of anti-GBM disease at one institution.

    Science.gov (United States)

    Nakabayashi, Kimimasa; Fujioka, Yasunori; Arimura, Yoshihiro; Fukuoka, Toshihito; Marumo, Tomohumi; Umino, Michiru; Kamiya, Yasushi; Okai, Takahiro; Tsurumaki, Shigeru; Nagasawa, Toshihiko; Yamada, Akira

    2011-08-01

    Anti-glomerular basement membrane (anti-GBM) disease is thought to be distinct from vasculitis. In contrast, there have been several papers suggesting the presence of angiitis in cases that were positive for anti-GBM antibody (Ab), as well as for either myeloperoxidase (MPO)- or proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA) (Group I). We experienced four patients who had anti-GBM Abs, but not MPO- and PR3-ANCA (Group II), and two of these patients were found to have vasculitis. Therefore, we performed an in-depth study on these two patients. The patients with anti-GBM disease were isolated from 578 cases whose renal tissues were examined, and they were categorized into two groups. We have already published the data about Group I. We then proceeded to study two vasculitic patients in Group II clinically, pathologically, and serologically. The anti-GBM Ab and ANCA levels were detected by enzyme-linked immunosorbent assays. Renal specimens were studied by routine staining as well as immunohistochemical investigations of CD31 and type IV collagen. The total number of patients with anti-GBM disease was 7 (7/578 = 1.2%), with 3 patients belonging to Group I and 4 patients belonging to Group II. Two patients in Group II were diagnosed to have vasculitis, but the remaining 2 patients did not. One vasculitic patient was complicated by pulmonary hemorrhage, while the other vasculitic patient displayed peripheral neuropathy as well as a small cavity lesion in the lung. The latter patient was found to be positive for perinuclear (p)-ANCA, but not for any other ANCA subsets. The renal pathology in the two vasculitic patients showed crescentic glomerulonephritis (CSGN) and immunoglobulin (Ig) G linear deposits along the glomerular capillary loops. The former patient showed fibrinoid angiitis in an afferent arteriole as well as peritubular capillaritis. The latter patient demonstrated peritubular capillaritis. These peritubular capillaritides were diagnosed by

  2. A low-latency pipeline for GRB light curve and spectrum using Fermi/GBM near real-time data

    Science.gov (United States)

    Zhao, Yi; Zhang, Bin-Bin; Xiong, Shao-Lin; Long, Xi; Zhang, Qiang; Song, Li-Ming; Sun, Jian-Chao; Wang, Yuan-Hao; Li, Han-Cheng; Bu, Qing-Cui; Feng, Min-Zi; Li, Zheng-Heng; Wen, Xing; Wu, Bo-Bing; Zhang, Lai-Yu; Zhang, Yong-Jie; Zhang, Shuang-Nan; Shao, Jian-Xiong

    2018-05-01

    Rapid response and short time latency are very important for Time Domain Astronomy, such as the observations of Gamma-ray Bursts (GRBs) and electromagnetic (EM) counterparts of gravitational waves (GWs). Based on near real-time Fermi/GBM data, we developed a low-latency pipeline to automatically calculate the temporal and spectral properties of GRBs. With this pipeline, some important parameters can be obtained, such as T 90 and fluence, within ∼ 20 min after the GRB trigger. For ∼ 90% of GRBs, T 90 and fluence are consistent with the GBM catalog results within 2σ errors. This pipeline has been used by the Gamma-ray Bursts Polarimeter (POLAR) and the Insight Hard X-ray Modulation Telescope (Insight-HXMT) to follow up the bursts of interest. For GRB 170817A, the first EM counterpart of GW events detected by Fermi/GBM and INTEGRAL/SPI-ACS, the pipeline gave T 90 and spectral information 21 min after the GBM trigger, providing important information for POLAR and Insight-HXMT observations.

  3. The Clinical and Immunologic Features of Patients With Combined Anti-GBM Disease and Castleman Disease.

    Science.gov (United States)

    Gu, Qiu-Hua; Jia, Xiao-Yu; Hu, Shui-Yi; Wang, Su-Xia; Zou, Wan-Zhong; Cui, Zhao; Zhao, Ming-Hui

    2018-06-01

    Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Decreased miR-106a inhibits glioma cell glucose uptake and proliferation by targeting SLC2A3 in GBM.

    Science.gov (United States)

    Dai, Dong-Wei; Lu, Qiong; Wang, Lai-Xing; Zhao, Wen-Yuan; Cao, Yi-Qun; Li, Ya-Nan; Han, Guo-Sheng; Liu, Jian-Min; Yue, Zhi-Jian

    2013-10-14

    MiR-106a is frequently down-regulated in various types of human cancer. However the underlying mechanism of miR-106a involved in glioma remains elusive. The association of miR-106a with glioma grade and patient survival was analyzed. The biological function and target of miR-106a were determined by bioinformatic analysis and cell experiments (Western blot, luciferase reporter, cell cycle, ntracellular ATP production and glucose uptake assay). Finally, rescue expression of its target SLC2A3 was used to test the role of SLC2A3 in miR-106a-mediated cell glycolysis and proliferation. Here we showed that miR-106a was a tumor suppressor miRNA was involved in GBM cell glucose uptake and proliferation. Decreased miR-106a in GBM tissues and conferred a poor survival of GBM patients. SLC2A3 was identified as a core target of miR-106a in GBM cells. Inhibition of SLC2A3 by miR-106a attenuated cell proliferation and inhibited glucose uptake. In addition, for each biological process we identified ontology-associated transcripts that significantly correlated with SLC2A3 expression. Finally, the expression of SLC2A3 largely abrogated miR-106a-mediated cell proliferation and glucose uptake in GBM cells. Taken together, miR-106a and SLC2A3 could be potential therapeutic approaches for GBM.

  5. Anti-GBM disease after nephrectomy for xanthogranulomatous pyelonephritis in a patient expressing HLA DR15 major histocompatibility antigens: a case report.

    Science.gov (United States)

    O'Hagan, Emma; Mallett, Tamara; Convery, Mairead; McKeever, Karl

    2015-01-01

    Antiglomerular basement membrane (anti-GBM) antibody disease is uncommon in the pediatric population. There are no cases in the literature describing the development of anti-GBM disease following XGP or nephrectomy. We report the case of a 7-year-old boy with no past history of urological illness, treated with antimicrobials and nephrectomy for diffuse, unilateral xanthogranulomatous pyelonephritis (XGP). Renal function and ultrasound scan of the contralateral kidney postoperatively were normal. Three months later, the child represented in acute renal failure with rapidly progressive glomerulonephritis requiring hemodialysis. Renal biopsy showed severe crescentic glomerulonephritis with 95% of glomeruli demonstrating circumferential cellular crescents. Strong linear IgG staining of the glomerular basement membranes was present, in keeping with anti-GBM disease. Circulating anti-GBM antibodies were positive. Treatment with plasma exchange, methylprednisolone, and cyclophosphamide led to normalization of anti-GBM antibody titers. Frequency of hemodialysis was reduced as renal function improved, and he is currently independent of dialysis with estimated glomerular filtration rate 20.7 mls/min/1.73 m 2 . Case studies in the adult literature have reported the development of a rapidly progressive anti-GBM antibody-induced glomerulonephritis following renal surgery where patients expressed HLA DR2/HLA DR15 major histocompatibility (MHC) antigens. Of note, our patient also expresses the HLA DR15 MHC antigen.

  6. GBM Observations of Be X-Ray Binary Outbursts

    Science.gov (United States)

    Wilson-Hodge, Colleen A.; Finger, M. H.; Jenke, P. A.

    2014-01-01

    Since 2008 we have been monitoring accreting pulsars using the Gamma ray Burst Monitor (GBM) on Fermi. This monitoring program includes daily blind full sky searches for previously unknown or previously quiescent pulsars and source specific analysis to track the frequency evolution of all detected pulsars. To date we have detected outbursts from 23 transient accreting pulsars, including 21 confirmed or likely Be/X-ray binaries. I will describe our techniques and highlight results for selected pulsars.

  7. Statistical properties of Fermi GBM GRBs' spectra

    Science.gov (United States)

    Rácz, István I.; Balázs, Lajos G.; Horvath, Istvan; Tóth, L. Viktor; Bagoly, Zsolt

    2018-03-01

    Statistical studies of gamma-ray burst (GRB) spectra may result in important information on the physics of GRBs. The Fermi GBM catalogue contains GRB parameters (peak energy, spectral indices, and intensity) estimated fitting the gamma-ray spectral energy distribution of the total emission (fluence, flnc), and during the time of the peak flux (pflx). Using contingency tables, we studied the relationship of the models best-fitting pflx and flnc time intervals. Our analysis revealed an ordering of the spectra into a power law - Comptonized - smoothly broken power law - Band series. This result was further supported by a correspondence analysis of the pflx and flnc spectra categorical variables. We performed a linear discriminant analysis (LDA) to find a relationship between categorical (spectral) and model independent physical data. LDA resulted in highly significant physical differences among the spectral types, that is more pronounced in the case of the pflx spectra, than for the flnc spectra. We interpreted this difference as caused by the temporal variation of the spectrum during the outburst. This spectral variability is confirmed by the differences in the low-energy spectral index and peak energy, between the pflx and flnc spectra. We found that the synchrotron radiation is significant in GBM spectra. The mean low-energy spectral index is close to the canonical value of α = -2/3 during the peak flux. However, α is ˜ -0.9 for the spectra of the fluences. We interpret this difference as showing that the effect of cooling is important only for the fluence spectra.

  8. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

    Science.gov (United States)

    Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

    2017-08-01

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

  9. Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, Cornelius [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); Moenninghoff, Christoph; Goericke, Sophia; Forsting, Michael; Umutlu, Lale [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kirchner, Julian [University Hospital Duesseldorf, Institute of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Koeppen, Susanne [University Hospital Essen, Department of Neurology, Essen (Germany); Binse, Ina; Poeppel, Thorsten D.; Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Hense, Joerg [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Schlamann, Marc [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Giessen, Department of Neuroradiology, Essen (Germany)

    2017-08-15

    The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM. (orig.)

  10. Survey of the effect of doxorubicin and flavonoid extract of white Morus alba leaf on apoptosis induction in a-172 GBM cell line.

    Science.gov (United States)

    Dabili, Sheyda; Fallah, Soudabeh; Aein, Mojdeh; Vatannejad, Akram; Panahi, Ghodratollah; Fadaei, Reza; Moradi, Nariman; Shojaii, Asie

    2018-02-20

    In this study, the effect of doxorubicin, flavonoid extract of white Morus alba leaf (MFE) and a combination of doxorubicin and flavonoid extract on Bax and Bcl2 levels and caspase 3 activity of cancer A-172 GBM cell line was investigated. Bax/Bcl2 levels of treated A-172 GBM cell line with flavonoid extract of white mulberry leaf were estimated by ELISA methods. Caspase 3 activity of treated A-172 GBM cells was determined by calorimetric assay. The flow cytometry assessment was used to estimate the apoptosis percent of treated A-172 GBM cells. Treatment of A-172 GBM cells with MFE, doxorubicin and a combination of MFE and doxorubicin caused a significant decrease in Bcl2 level and an increase in Bax level. The apoptosis percent of treated cells were also elevated significantly. Present results suggest that concomitant use of herbal medicine and chemotherapy may be an effective alternative method for the treatment of cancers.

  11. Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

    Science.gov (United States)

    Kim, Ju Han; Ha, Il Soo; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang

    2004-11-01

    Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

  12. VizieR Online Data Catalog: New spectral lag measurements of 50 Fermi/GBM GRBs (Shao+, 2017)

    Science.gov (United States)

    Shao, L.; Zhang, B.-B.; Wang, F.-R.; Wu, X.-F.; Cheng, Y.-H.; Zhang, Xi; Yu, B.-Y.; Xi, B.-J.; Wang, X.; Feng, H.-X.; Zhang, M.; Xu, D.

    2018-03-01

    This work made extensive use of the data from the Gamma-Ray Burst Monitor (GBM) on board the Fermi Gamma-ray Space Telescope. For the first step, we searched in the official GBM online burst catalog (Gruber+ 2014ApJS..211...12G ; von Kienlin+ 2014, J/ApJS/211/13) for bright bursts with a total fluence F>5x10-6erg/cm-2 in 10-1000keV. See section 2 for the details on the sample selection. (1 data file).

  13. The effect of silver nanoparticles (AgNPs) on proliferation and apoptosis of in ovo cultured glioblastoma multiforme (GBM) cells.

    Science.gov (United States)

    Urbańska, Kaja; Pająk, Beata; Orzechowski, Arkadiusz; Sokołowska, Justyna; Grodzik, Marta; Sawosz, Ewa; Szmidt, Maciej; Sysa, Paweł

    2015-01-01

    Recently, it has been shown that silver nanoparticles (AgNPs) provide a unique approach to the treatment of tumors, especially those of neuroepithelial origin. Thus, the aim of this study was to evaluate the impact of AgNPs on proliferation and activation of the intrinsic apoptotic pathway of glioblastoma multiforme (GBM) cells cultured in an in ovo model. Human GBM cells, line U-87, were placed on chicken embryo chorioallantoic membrane. After 8 days, the tumors were divided into three groups: control (non-treated), treated with colloidal AgNPs (40 μg/ml), and placebo (tumors supplemented with vehicle only). At the end of the experiment, all tumors were isolated. Assessment of cell proliferation and cell apoptosis was estimated by histological, immunohistochemical, and Western blot analyses. The results show that AgNPs can influence GBM growth. AgNPs inhibit proliferation of GBM cells and seem to have proapoptotic properties. Although there were statistically significant differences between control and AgNP groups in the AI and the levels of active caspase 9 and active caspase 3, the level of these proteins in GBM cells treated with AgNPs seems to be on the border between the spontaneous apoptosis and the induced. Our results indicate that the antiproliferative properties of silver nanoparticles overwhelm proapoptotic ones. Further research focused on the cytotoxic effect of AgNPs on tumor and normal cells should be conducted.

  14. Glioblastoma (GBM) effects on quantitative MRI of contralateral normal appearing white matter.

    Science.gov (United States)

    Mehrabian, Hatef; Lam, Wilfred W; Myrehaug, Sten; Sahgal, Arjun; Stanisz, Greg J

    2018-03-28

    The objective was to investigate (with quantitative MRI) whether the normal appearing white matter (NAWM) of glioblastoma (GBM) patients on the contralateral side (cNAWM) was different from NAWM of healthy controls. Thirteen patients with newly diagnosed GBM and nine healthy age-matched controls were MRI-scanned with quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), and transverse relaxation time (T 2 )-mapping. MRI scans were performed after surgery and before chemo-radiation treatment. Comprehensive qMT, CEST, T 2 data were acquired. A two-pool MT model was fit to qMT data in transient state, to calculate MT model parameters [Formula: see text]. CEST signal was isolated by removing the contributions from the MT and direct water saturation, and CEST signal was calculated for Amide (CEST Amide ), Amine (CEST Amine ) and nuclear overhauser effect, NOE (CEST NOE ). There was no difference between GBM patients and normal controls in the qMT properties of the macromolecular pool [Formula: see text]. However, their free water pool spectrum was different (1/R a T 2a , patient  = 28.1 ± 3.9, 1/R a T 2a , control  = 25.0 ± 1.1, p = 0.03). This difference could be attributed to the difference in their T 2 time ([Formula: see text] = 83 ± 4, [Formula: see text] = 88 ± 1, p = 0.004). CEST signals were statistically significantly different with the CEST Amide having the largest difference between the two cohorts (CEST Amide,patient  = 2.8 ± 0.4, CEST Amide,control  = 3.4 ± 0.5, p = 0.009). CEST in cNAWM of GBM patients was lower than healthy controls which could be caused by modified brain metabolism due to tumor cell infiltration. There was no difference in MT properties of the patients and controls, however, the differences in free water pool properties were mainly due to reduced T 2 in cNAWM of the patients (resulting from structural changes and increased cellularity).

  15. Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM.

    Directory of Open Access Journals (Sweden)

    Juan Li

    Full Text Available Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells and human hepatocellular carcinoma (Hep-G2 cells. Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP family members,(e.g., survivin and XIAP by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM.

  16. Saponin 1 Induces Apoptosis and Suppresses NF-κB-Mediated Survival Signaling in Glioblastoma Multiforme (GBM)

    Science.gov (United States)

    Tang, Chi; Li, Bo; Wang, Yuangang; Gao, Zhenhui; Luo, Peng; Yin, Anan; Wang, Xiaoyang; Cheng, Guang; Fei, Zhou

    2013-01-01

    Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM. PMID:24278406

  17. Direction Dependent Background Fitting for the Fermi GBM Data

    OpenAIRE

    Szécsi, Dorottya; Bagoly, Zsolt; Kóbori, József; Horváth, István; Balázs, Lajos G.

    2013-01-01

    We present a method for determining the background of Fermi GBM GRBs using the satellite positional information and a physical model. Since the polynomial fitting method typically used for GRBs is generally only indicative of the background over relatively short timescales, this method is particularly useful in the cases of long GRBs or those which have Autonomous Repoint Request (ARR) and a background with much variability on short timescales. We give a Direction Dependent Background Fitting...

  18. SU-F-R-04: Radiomics for Survival Prediction in Glioblastoma (GBM)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Molitoris, J; Bhooshan, N; Choi, W; Lu, W; Mehta, M; D’Souza, W [University of Maryland School of Medicine, Baltimore, MD (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Giacomelli, I; Scartoni, D [University of Florence, Florence (Italy); Gzell, C [Northern Sydney Cancer Centre, Sydney (Australia)

    2016-06-15

    Purpose: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). Methods: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection, whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92). Conclusion: Radiomics approach combined with patients’ demographics and clinical parameters can

  19. Investigating tumor perfusion by hyperpolarized (13) C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts

    DEFF Research Database (Denmark)

    Park, Ilwoo; von Morze, Cornelius; Lupo, Janine M

    2016-01-01

    glioblastoma (GBM) model for the characterization of tumor perfusion and compared with standard Gd-based dynamic susceptibility contrast (DSC) MRI data and immunohistochemical analysis from resected brains. Distinct HMCP perfusion characteristics were observed within the GBM tumors compared with contralateral...... for tumor that exhibited high levels of hyperpolarized HMCP signal. The results from this study have demonstrated that hyperpolarized HMCP data can be used as an indicator of tumor perfusion in an orthotopic xenograft model for GBM. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc....

  20. Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

    Science.gov (United States)

    Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

    2014-04-15

    Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

  1. Metformin inhibits TGF-β1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.

    Science.gov (United States)

    Song, Yang; Chen, Yong; Li, Yunqian; Lyu, Xiaoyan; Cui, Jiayue; Cheng, Ye; Zhao, Liyan; Zhao, Gang

    2018-01-23

    Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis is still relatively poor. The invasive property of GBM is the major cause of death in patients. Epithelial-to-mesenchymal transition-like process (EMT-like process) is considered to play an important role in the invasive property. Metformin has been reported as a regulator of EMT-like process. In this study, we confirmed that metformin inhibited TGF-β1-induced EMT-like process and EMT-associated migration and invasion in LN18 and U87 GBM cells. Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells. We further clarified that metformin specifically inhibited TGF-β1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1. Taken together, our data demonstrate that metformin inhibits TGF-β1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.

  2. A survival analysis of GBM patients in the West of Scotland pre- and post-introduction of the Stupp regime.

    Science.gov (United States)

    Teo, Mario; Martin, Sean; Owusu-Agyemang, Kevin; Nowicki, Stefan; Clark, Brian; Mackinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

    2014-06-01

    It is now accepted that the concomitant administration of temozolomide with radiotherapy (Stupp regime), in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM), significantly improves survival and this practice has been adopted locally since 2004. However, survival outcomes in cancer can vary in different population groups, and outcomes can be affected by a number of local factors including socioeconomic status. In the West of Scotland, we have one of the worse socioeconomic status and overall health record for a western European country. With the ongoing reorganisation and rationalisation in the National Health Service, the addition of prolonged courses of chemotherapy to patients' management significantly adds to the financial burden of a cash stripped NHS. A survival analysis in patients with GBM was therefore performed, comparing outcomes of pre- and post-introduction of the Stupp regime, to justify the current practice. Prospectively collected clinical data were analysed in 105 consecutive patients receiving concurrent chemoradiotherapy (Stupp regime) following surgical treatment of GBM between December 2004 and February 2009. This was compared to those of 106 consecutive GBM patients who had radical radiotherapy (pre-Stupp regime) post-surgery between January 2001 and February 2006. The median overall survival for the post-Stupp cohort was 15.3 months (range, 2.83-50.5 months), with 1-year and 2-year overall survival rates of 65.7% and 19%, respectively. This was in comparison with the median overall pre-Stupp survival of 10.7 months, with 1-year and 2-year survival rates of 42.6% and 12%, respectively (log-rank test, p GBM patients in the West of Scotland.

  3. A PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance.

    Science.gov (United States)

    Yan, Xiaoyan; Zhang, Chuanbao; Liang, Tingyu; Yang, Fan; Wang, Haoyuan; Wu, Fan; Wang, Wen; Wang, Zheng; Cheng, Wen; Xu, Jiangnan; Jiang, Tao; Chen, Jing; Ding, Yaozhong

    2017-10-17

    Collagen XVII expression has recently been demonstrated to be correlated with the tumor malignance. While Collagen XVII is known to be widely distributed in neurons of the human brain, its precise role in pathogenesis of glioblastoma multiforme (GBM) is unknown. In this study, we identified and characterized a new PTEN-COL17A1 fusion gene in GMB using transcriptome sequencing. Although fusion gene did not result in measurable fusion protein production, its presence is accompanied with high levels of COL17A1 expression, revealed a novel regulatory mechanism of Collagen XVII expression by PTEN-COL17A1 gene fusion. Knocked down Collagen XVII expression in glioma cell lines resulted in decreased tumor invasiveness, along with significant reduction of MMP9 expression, while increased Collagen XVII expression promotes invasive activities of glioma cells and associated with GBM recurrences. Together, our results uncovered a new PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance, and demonstrated that COL17A1 could serve as a useful prognostic biomarker and therapeutic targets for GBM.

  4. Seroadaptive Strategies of Gay & Bisexual Men (GBM) with the Highest Quartile Number of Sexual Partners in Vancouver, Canada.

    Science.gov (United States)

    Card, Kiffer G; Lachowsky, Nathan J; Cui, Zishan; Sereda, Paul; Rich, Ashleigh; Jollimore, Jody; Howard, Terry; Birch, Robert; Carter, Allison; Montaner, Julio; Moore, David; Hogg, Robert S; Roth, Eric Abella

    2017-05-01

    Despite continued research among men with more sexual partners, little information exists on their seroadaptive behavior. Therefore, we examined seroadaptive anal sex strategies among 719 Vancouver gay and bisexual men (GBM) recruited using respondent-driven sampling. We provide descriptive, bivariable, and multivariable adjusted statistics, stratified by HIV status, for the covariates of having ≥7 male anal sex partners in the past 6 months (Population fourth quartile versus <7). Sensitivity Analysis were also performed to assess the robustness of this cut-off. Results suggest that GBM with more sexual partners are more likely to employ seroadaptive strategies than men with fewer partners. These strategies may be used in hopes of offsetting risk, assessing needs for subsequent HIV testing, and balancing personal health with sexual intimacy. Further research is needed to determine the efficacy of these strategies, assess how GBM perceive their efficacy, and understand the social and health impacts of their widespread uptake.

  5. Discontinuation of Hemodialysis in a Patient with Anti-GBM Disease by the Treatment with Corticosteroids and Plasmapheresis despite Several Predictors for Dialysis-Dependence

    Directory of Open Access Journals (Sweden)

    Yoshihide Fujigaki

    2017-01-01

    Full Text Available A 26-year-old man highly suspected of having antiglomerular basement membrane (GBM disease was treated with corticosteroid pulse therapy 9 days after initial infection-like symptoms with high procalcitonin value. The patient required hemodialysis the next day of the treatment due to oliguria. In addition to corticosteroid therapy, plasmapheresis was introduced and the patient could discontinue hemodialysis 43 days after the treatment. Kidney biopsy after initiation of hemodialysis confirmed anti-GBM disease with 86.3% crescent formation. Physician should keep in mind that active anti-GBM disease shows even high procalcitonin value in the absence of infection. To pursue recovery of renal function, the challenge of the immediate and persistent treatment with high-dose corticosteroids plus plasmapheresis for highly suspected anti-GBM disease is vitally important despite the presence of reported predictors for dialysis-dependence including oliguria and requiring hemodialysis at presentation.

  6. An Ordinary Short Gamma-Ray Burst with Extraordinary Implications: Fermi -GBM Detection of GRB 170817A

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, A.; Roberts, O. J.; Connaughton, V. [Science and Technology Institute, Universities Space Research Association, Huntsville, AL 35805 (United States); Veres, P.; Briggs, M. S.; Hamburg, R.; Preece, R. D.; Poolakkil, S. [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States); Burns, E.; Racusin, J.; Canton, T. Dal [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Kocevski, D.; Wilson-Hodge, C. A.; Hui, C. M.; Littenberg, T. [Astrophysics Office, ST12, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Kienlin, A. von [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Christensen, N.; Broida, J. [Physics and Astronomy, Carleton College, MN 55057 (United States); Siellez, K. [Center for Relativistic Astrophysics and School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Blackburn, L., E-mail: Adam.M.Goldstein@nasa.gov [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); and others

    2017-10-20

    On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.

  7. Temozolomide, sirolimus and chloroquine is a new therapeutic combination that synergizes to disrupt lysosomal function and cholesterol homeostasis in GBM cells.

    Science.gov (United States)

    Hsu, Sanford P C; Kuo, John S; Chiang, Hsin-Chien; Wang, Hsin-Ell; Wang, Yu-Shan; Huang, Cheng-Chung; Huang, Yi-Chun; Chi, Mau-Shin; Mehta, Minesh P; Chi, Kwan-Hwa

    2018-01-23

    Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM. This repurposed triple therapy combination induced GBM apoptosis in vitro and inhibited GBM xenograft growth in vivo . Cytotoxicity is caused by induction of lysosomal membrane permeabilization and release of hydrolases, and may be rescued by cholesterol supplementation. Triple treatment inhibits lysosomal function, prevents cholesterol extraction from low density lipoprotein (LDL), and causes clumping of lysosome associated membrane protein-1 (LAMP-1) and lipid droplets (LD) accumulation. Co-treatment of the cell lines with inhibitor of caspases and cathepsin B only partially reverse of cytotoxicities, while N-acetyl cysteine (NAC) can be more effective. A combination of reactive oxygen species (ROS) generation from cholesterol depletion are the early event of underling mechanism. Cholesterol repletion abolished the ROS production and reversed the cytotoxicity from QRT treatment. The shortage of free cholesterol destabilizes lysosomal membranes converting aborted autophagy to apoptosis through either direct mitochondria damage or cathepsin B release. This promising anti-GBM triple therapy combination severely decreases mitochondrial function, induces lysosome-dependent apoptotic cell death, and is now poised for further clinical testing and validation.

  8. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

    Science.gov (United States)

    McAdoo, Stephen P; Tanna, Anisha; Hrušková, Zdenka; Holm, Lisa; Weiner, Maria; Arulkumaran, Nishkantha; Kang, Amy; Satrapová, Veronika; Levy, Jeremy; Ohlsson, Sophie; Tesar, Vladimir; Segelmark, Mårten; Pusey, Charles D

    2017-09-01

    Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Fermi/GBM Update on the Orbital Ephemeris of Swift J0243.6+6124

    Science.gov (United States)

    Jenke, P.; Wilson-Hodge, C. A.; Malacaria, C.

    2018-02-01

    Using Fermi/GBM data between MJD 58098 and 58154 (2017 December 11 to 2018 February 5) in the 12-50 keV range, we determine a new orbital ephemeris for the newly discovered (ATEL #10809) Be X-ray binary Swift J0243.6+6124.

  10. MAXIMIZATION OF DNA DAMAGE TO MGMT(+ EGFR(+ GBM CELLS USING OPTIMAL COMBINATION OF TEMOZOLOMIDE-ANTI EGFR MONOCLONAL ANTIBODY NIMOTUZUMAB

    Directory of Open Access Journals (Sweden)

    M. A. M. Inggas

    2015-09-01

    Full Text Available Background: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor in adultswith dismal prognosis due to the unavailability of an effective therapy. Up to now, there had been no definitive studies published on EGFR inhibition therapy as a chemosensitizer for GBM therapy using Temozolomide (TMZ. This study aims to reveal the most effective method and timing to administer TMZ-anti EGFR targeted therapy which causes maximal DNA damage on GBM cells.Methods: Various regimens of anti EGFR monoclonal antibody Nimotuzumab (NMZ was administered in different combinations with TMZ, performed on U87MG MGMT(+ EGFR(+ cells. The effectiveness of the combinations were evaluated by measuring yH2AX levels which reflects the degree of DNA damage. One-way Anova and LSD tests were performed to determine the effects of each treatment with p<0.05. Results and discussion: the mean SD of yH2AX of each treatment was: 11,90±1,25 for the control group; 29.33±1.91 for NMZ alone; 28.13±1.58 for TMZ alone; 41.53±3.51 for concurrent use; 35.67 ±2.65 for NMZ after 24 hours TMZ; 31.87±2.94 for NMZ after 48 hours TMZ; 39.57±4.2 for TMZ after 24 hours NMZ; and 35.93 ±3.56 for TMZ after 48 hours NMZ. The administration of TMZ concurrent with or after 24 hours NMZ gives the highest amount of DNA damage to GBM cells. Conclusion: The administration of Nimotuzumab targeted therapy up to 24 hours before Temozolomide chemotherapy has been proven to be effective in maximizing the amount of DNA damage done to GBM cells in vitro. 

  11. Circulating gamma delta T cells are activated and depleted during progression of high-grade gliomas: Implications for gamma delta T cell therapy of GBM

    Science.gov (United States)

    Glioblastoma multiforme (GBM) remains frustratingly impervious to any existing therapy. We have previously shown that GBM is sensitive to recognition and lysis by ex vivo activated gamma delta T cells, a minor subset of lymphocytes that innately recognize autologous stress-associated target antigens...

  12. Routinely used immunoassays do not detect circulating anti-GBM antibodies against native NC1 hexamer and EA epitope of the α3 chain of type IV collagen.

    Science.gov (United States)

    Clavarino, Giovanna; Gauthier, Arnaud; Hellmark, Thomas; Carron, Pierre-Louis; Giovannini, Diane; Colliard, Sophie; Dragon-Durey, Marie-Agnès; Segelmark, Mårten; Cesbron, Jean-Yves; Dumestre-Pérard, Chantal

    2018-04-12

    Detection of circulating anti-GBM antibodies has a key role for the diagnosis of Goodpasture syndrome but immunoassays using purified or recombinant alpha3(IV)NC1 as antigen do not recognize all anti-GBM antibodies. We show that anti-GBM antibodies directed against epitopes in their native conformation or cryptic epitopes are detected by indirect immunofluorescence. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models.

    Science.gov (United States)

    Salazar, Nicole; Carlson, Jeffrey C; Huang, Kexin; Zheng, Yayue; Oderup, Cecilia; Gross, Julia; Jang, Andrew D; Burke, Thomas M; Lewén, Susanna; Scholz, Alexander; Huang, Serina; Nease, Leona; Kosek, Jon; Mittelbronn, Michel; Butcher, Eugene C; Tu, Hua; Zabel, Brian A

    2018-05-02

    Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG 1 ) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells. We used hydrodynamic gene transfer to overexpress the antibody, with efficacy in vivo. X7Ab kills GBM tumor cells and ACKR3-expressing vascular endothelial cells by engaging the cytotoxic activity of natural killer (NK) cells and complement and the phagocytic activity of macrophages. Combining X7Ab with TMZ allows the TMZ dosage to be lowered, without compromising therapeutic efficacy. Mice treated with X7Ab and in combination with TMZ showed significant tumor reduction by MRI and longer survival overall. Brain-tumor-infiltrating leukocyte analysis revealed that X7Ab enhances the activation of M1 macrophages to support anti-tumor immune response in vivo. Targeting ACKR3 with immunotherapeutic monoclonal antibodies (mAbs) in combination with standard of care therapies may prove effective in treating GBM. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells.

    Science.gov (United States)

    Tang, Nou-Ying; Chueh, Fu-Shin; Yu, Chien-Chih; Liao, Ching-Lung; Lin, Jen-Jyh; Hsia, Te-Chun; Wu, King-Chuen; Liu, Hsin-Chung; Lu, Kung-Wen; Chung, Jing-Gung

    2016-04-01

    Glioblastoma multiforme (GBM) is a highly malignant devastating brain tumor in adults. Benzyl isothiocyanate (BITC) is one of the isothiocyanates that have been shown to induce human cancer cell apoptosis and cell cycle arrest. Herein, the effect of BITC on cell viability and apoptotic cell death and the genetic levels of human brain glioblastoma GBM 8401 cells in vitro were investigated. We found that BITC induced cell morphological changes, decreased cell viability and the induction of cell apoptosis in GBM 8401 cells was time-dependent. cDNA microarray was used to examine the effects of BITC on GBM 8401 cells and we found that numerous genes associated with cell death and cell cycle regulation in GBM 8401 cells were altered after BITC treatment. The results show that expression of 317 genes was upregulated, and two genes were associated with DNA damage, the DNA-damage-inducible transcript 3 (DDIT3) was increased 3.66-fold and the growth arrest and DNA-damage-inducible α (GADD45A) was increased 2.34-fold. We also found that expression of 182 genes was downregulated and two genes were associated with receptor for cell responses to stimuli, the EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1) was inhibited 2.01-fold and the TNF receptor-associated protein 1 (TRAP1) was inhibited 2.08-fold. BITC inhibited seven mitochondria ribosomal genes, the mitochondrial ribosomal protein; tumor protein D52 (MRPS28) was inhibited 2.06-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein L23 (MRPL23) decreased 2.08-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein S12 (MRPS12) decreased 2.08-fold, the mitochondria ribosomal protein L12 (MRPL12) decreased 2.25-fold and the mitochondria ribosomal protein S34 (MRPS34) was decreased 2.30-fold in GBM 8401 cells. These changes of gene expression can provide the effects of BITC on the genetic level and are

  15. On the Interpretation of the Fermi-GBM Transient Observed in Coincidence with LIGO Gravitational-wave Event GW150914

    Science.gov (United States)

    Connaughton, V.; Burns, E.; Goldstein, A.; Blackburn, L.; Briggs, M. S.; Christensen, N.; Hui, C. M.; Kocevski, D.; Littenberg, T.; McEnery, J. E.; Racusin, J.; Shawhan, P.; Veitch, J.; Wilson-Hodge, C. A.; Bhat, P. N.; Bissaldi, E.; Cleveland, W.; Giles, M. M.; Gibby, M. H.; von Kienlin, A.; Kippen, R. M.; McBreen, S.; Meegan, C. A.; Paciesas, W. S.; Preece, R. D.; Roberts, O. J.; Stanbro, M.; Veres, P.

    2018-01-01

    The weak transient detected by the Fermi Gamma-ray Burst Monitor (GBM) 0.4 s after GW150914 has generated much speculation regarding its possible association with the black hole binary merger. Investigation of the GBM data by Connaughton et al. revealed a source location consistent with GW150914 and a spectrum consistent with a weak, short gamma-ray burst. Greiner et al. present an alternative technique for fitting background-limited data in the low-count regime, and call into question the spectral analysis and the significance of the detection of GW150914-GBM presented in Connaughton et al. The spectral analysis of Connaughton et al. is not subject to the limitations of the low-count regime noted by Greiner et al. We find Greiner et al. used an inconsistent source position and did not follow the steps taken in Connaughton et al. to mitigate the statistical shortcomings of their software when analyzing this weak event. We use the approach of Greiner et al. to verify that our original spectral analysis is not biased. The detection significance of GW150914-GBM is established empirically, with a false-alarm rate (FAR) of ∼ {10}-4 Hz. A post-trials false-alarm probability (FAP) of 2.2× {10}-3 (2.9σ ) of this transient being associated with GW150914 is based on the proximity in time to the gravitational-wave event of a transient with that FAR. The FAR and the FAP are unaffected by the spectral analysis that is the focus of Greiner et al.

  16. Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

    Science.gov (United States)

    Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; Biswas, Nidhan K; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N; Deb, Sumit; Saha, Suniti K; Chowdhury, Anup K; Ghosh, Subhashish; Rudin, Charles M; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

  17. FERMI GBM OBSERVATIONS OF V404 CYG DURING ITS 2015 OUTBURST

    Energy Technology Data Exchange (ETDEWEB)

    Jenke, P. A.; Veres, P.; Briggs, M. S.; Burns, E. [University of Alabama in Huntsville, Huntsville, AL 35805 (United States); Wilson-Hodge, C. A.; Hui, M. [Marshall Space Flight Center, Huntsville, AL 35812 (United States); Homan, Jeroen [MIT Kavli Institute for Astrophysics and Space Research, 77 Massachusetts Avenue 37-582D, Cambridge, MA 02139 (United States); Connaughton, V.; Finger, M. H., E-mail: peter.a.jenke@nasa.gov [Universities Space Research Association, Huntsville, AL 35805 (United States)

    2016-07-20

    V404 Cygni was discovered in 1989 by the Ginga X-ray satellite during its only previously observed X-ray outburst and soon after confirmed as a black hole binary. On 2015 June 15, the Gamma-ray Burst Monitor (GBM) triggered on a new outburst of V404 Cygni. We present 13 days of GBM observations of this outburst, including Earth occultation flux measurements and spectral and temporal analysis. The Earth occultation fluxes reached 30 Crab with detected emission to 100 keV and determined, via hardness ratios, that the source was in a hard state. At high luminosity, spectral analysis between 8 and 300 keV showed that the electron temperature decreased with increasing luminosity. This is expected if the protons and electrons are in thermal equilibrium during an outburst with the electrons cooled by the Compton scattering of softer seed photons from the disk. However, the implied seed photon temperatures are unusually high, suggesting a contribution from another source, such as the jet. No evidence of state transitions is seen during this time period. The temporal analysis reveals power spectra that can be modeled with two or three strong, broad Lorentzians, similar to the power spectra of black hole binaries in their hard state.

  18. Combinatorial Drug Testing in 3D Microtumors Derived from GBM Patient-Derived Xenografts Reveals Cytotoxic Synergy in Pharmacokinomics-informed Pathway Interactions.

    Science.gov (United States)

    Gilbert, Ashley N; Anderson, Joshua C; Duarte, Christine W; Shevin, Rachael S; Langford, Catherine P; Singh, Raj; Gillespie, G Yancey; Willey, Christopher D

    2018-05-30

    Glioblastoma multiforme (GBM), the most common form of primary malignant brain cancer in adults, is a devastating disease for which effective treatment has remained elusive for over 75 years. One reason for the minimal progress during this time is the lack of accurate preclinical models to represent the patient's tumor's in vivo environment, causing a disconnect in drug therapy effectiveness between the laboratory and clinic. While patient-derived xenografts (PDX's or xenolines) are excellent human tumor representations, they are not amenable to high throughput testing. Therefore, we developed a miniaturized xenoline system (microtumors) for drug testing. Nineteen GBM xenolines were profiled for global kinase (kinomic) activity revealing actionable kinase targets associated with intracranial tumor growth rate. Kinase inhibitors for these targets (WP1066, selumetinib, crizotinib, and cediranib) were selected for single and combination therapy using a fully human-derived three-dimensional (3D) microtumor model of GBM xenoline cells embedded in HuBiogel for subsequent molecular and phenotype assays. GBM microtumors closely resembled orthotopically-implanted tumors based on immunohistochemical analysis and displayed kinomic and morphological diversity. Drug response testing could be reproducibly performed in a 96-well format identifying several synergistic combinations. Our findings indicate that 3D microtumors can provide a suitable high-throughput model for combination drug testing.

  19. Experimental anti-GBM nephritis as an analytical tool for studying spontaneous lupus nephritis.

    Science.gov (United States)

    Du, Yong; Fu, Yuyang; Mohan, Chandra

    2008-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that results in immune-mediated damage to multiple organs. Among these, kidney involvement is the most common and fatal. Spontaneous lupus nephritis (SLN) in mouse models has provided valuable insights into the underlying mechanisms of human lupus nephritis. However, SLN in mouse models takes 6-12 months to manifest; hence there is clearly the need for a mouse model that can be used to unveil the pathogenic processes that lead to immune nephritis over a shorter time frame. In this article more than 25 different molecules are reviewed that have been studied both in the anti-glomerular basement membrane (anti-GBM) model and in SLN and it was found that these molecules influence both diseases in a parallel fashion, suggesting that the two disease settings share common molecular mechanisms. Based on these observations, the authors believe the experimental anti-GBM disease model might be one of the best tools currently available for uncovering the downstream molecular mechanisms leading to SLN.

  20. DISTRIBUTION OF GBM HEPARAN-SULFATE PROTEOGLYCAN CORE PROTEIN AND SIDE-CHAINS IN HUMAN GLOMERULAR-DISEASES

    NARCIS (Netherlands)

    VANDENBORN, J; VANDENHEUVEL, LPWJ; BAKKER, MAH; VEERKAMP, JH; ASSMANN, KJM; WEENING, JJ; BERDEN, JHM

    Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve

  1. Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

    Science.gov (United States)

    Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

    2015-01-01

    Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

  2. Techniques for Targeted Fermi-GBM Follow-Up of Gravitational-Wave Events

    Science.gov (United States)

    Blackburn, L.; Camp, J.; Briggs, M. S.; Connaughton, V.; Jenke, P.; Christensen, N.; Veitch, J.

    2012-01-01

    The Advanced LIGO and Advanced Virgo ground-based gravitational-wave (GW) detectors are projected to come online 2015 2016, reaching a final sensitivity sufficient to observe dozens of binary neutron star mergers per year by 2018. We present a fully-automated, targeted search strategy for prompt gamma-ray counterparts in offline Fermi-GBM data. The multi-detector method makes use of a detailed model response of the instrument, and benefits from time and sky location information derived from the gravitational-wave signal.

  3. MODELING THE AFTERGLOW OF THE POSSIBLE FERMI -GBM EVENT ASSOCIATED WITH GW150914

    International Nuclear Information System (INIS)

    Morsony, Brian J.; Workman, Jared C.; Ryan, Dominic M.

    2016-01-01

    We model the possible afterglow of the Fermi Gamma-ray Burst Monitor (GBM) event associated with LIGO detection GW150914, under the assumption that the gamma-rays are produced by a short GRB-like relativistic outflow. We model GW150914-GBM as both a weak, on-axis short GRB and normal short GRB seen far off-axis. Given the large uncertainty in the position of GW150914, we determine that the best chance of finding the afterglow is with ASKAP or possibly the Murchinson Widefield Array (MWA), with the flux from an off-axis short GRB reaching 0.2–4 mJy (0.12–16 mJy) at 150 MHz (863.5 MHz) by 1–12 months after the initial event. At low frequencies, the source would evolve from a hard to soft spectrum over several months. The radio afterglow would be detectable for several months to years after it peaks, meaning the afterglow may still be detectable and increasing in brightness NOW (2016 mid-July). With a localization from the MWA or ASKAP, the afterglow would be detectable at higher radio frequencies with the ATCA and in X-rays with Chandra or XMM .

  4. MODELING THE AFTERGLOW OF THE POSSIBLE FERMI -GBM EVENT ASSOCIATED WITH GW150914

    Energy Technology Data Exchange (ETDEWEB)

    Morsony, Brian J. [Department of Astronomy, University of Maryland, 1113 Physical Sciences Complex, College Park, MD 20742-2421 (United States); Workman, Jared C. [Department of Physical and Environmental Sciences, Colorado Mesa University, Grand Junction, CO 81501 (United States); Ryan, Dominic M., E-mail: morsony@astro.umd.edu [Department of Astronomy, University of California, Berkeley, 501 Campbell Hall #3411, Berkeley, CA 94720-3411 (United States)

    2016-07-10

    We model the possible afterglow of the Fermi Gamma-ray Burst Monitor (GBM) event associated with LIGO detection GW150914, under the assumption that the gamma-rays are produced by a short GRB-like relativistic outflow. We model GW150914-GBM as both a weak, on-axis short GRB and normal short GRB seen far off-axis. Given the large uncertainty in the position of GW150914, we determine that the best chance of finding the afterglow is with ASKAP or possibly the Murchinson Widefield Array (MWA), with the flux from an off-axis short GRB reaching 0.2–4 mJy (0.12–16 mJy) at 150 MHz (863.5 MHz) by 1–12 months after the initial event. At low frequencies, the source would evolve from a hard to soft spectrum over several months. The radio afterglow would be detectable for several months to years after it peaks, meaning the afterglow may still be detectable and increasing in brightness NOW (2016 mid-July). With a localization from the MWA or ASKAP, the afterglow would be detectable at higher radio frequencies with the ATCA and in X-rays with Chandra or XMM .

  5. The role of Gliadel wafers in the treatment of newly diagnosed GBM: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xing WK

    2015-06-01

    Full Text Available Wei-kang Xing,1 Chuan Shao,2 Zhen-yu Qi,1 Chao Yang,1 Zhong Wang1 1Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 2Department of Neurosurgery, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China Background: Standard treatment for high-grade glioma (HGG includes surgery followed by radiotherapy and/or chemotherapy. Insertion of carmustine wafers into the resection cavity as a treatment for malignant glioma is currently a controversial topic among neurosurgeons. Our meta-analysis focused on whether carmustine wafer treatment could significantly benefit the survival of patients with newly diagnosed glioblastoma multiforme (GBM.Method: We searched the PubMed and Web of Science databases without any restrictions on language using the keywords “Gliadel wafers”, “carmustine wafers”, “BCNU wafers”, or “interstitial chemotherapy” in newly diagnosed GBM for the period from January 1990 to March 2015. Randomized controlled trials (RCTs and cohort studies/clinical trials that compared treatments designed with and without carmustine wafers and which reported overall survival or hazard ratio (HR or survival curves were included in this study. Moreover, the statistical analysis was conducted by the STATA 12.0 software.Results: Six studies including two RCTs and four cohort studies, enrolling a total of 513 patients (223 with and 290 without carmustine wafers, matched the selection criteria. Carmustine wafers showed a strong advantage when pooling all the included studies (HR =0.63, 95% confidence interval (CI =0.49–0.81; P=0.019. However, the two RCTs did not show a statistical increase in survival in the group with carmustine wafer compared to the group without it (HR =0.51, 95% CI =0.18–1.41; P=0.426, while the cohort studies demonstrated a significant survival increase (HR =0.59, 95% CI =0.44–0.79; P<0.0001.Conclusion

  6. Test of the Weak Equivalence Principle using LIGO observations of GW150914 and Fermi observations of GBM transient 150914

    Directory of Open Access Journals (Sweden)

    Molin Liu

    2017-07-01

    Full Text Available About 0.4 s after the Laser Interferometer Gravitational-Wave Observatory (LIGO detected a transient gravitational-wave (GW signal GW150914, the Fermi Gamma-ray Burst Monitor (GBM also found a weak electromagnetic transient (GBM transient 150914. Time and location coincidences favor a possible association between GW150904 and GBM transient 150914. Under this possible association, we adopt Fermi's electromagnetic (EM localization and derive constraints on possible violations of the Weak Equivalence Principle (WEP from the observations of two events. Our calculations are based on four comparisons: (1 The first is the comparison of the initial GWs detected at the two LIGO sites. From the different polarizations of these initial GWs, we obtain a limit on any difference in the parametrized post-Newtonian (PPN parameter Δγ≲10−10. (2 The second is a comparison of GWs and possible EM waves. Using a traditional super-Eddington accretion model for GBM transient 150914, we again obtain an upper limit Δγ≲10−10. Compared with previous results for photons and neutrinos, our limits are five orders of magnitude stronger than those from PeV neutrinos in blazar flares, and seven orders stronger than those from MeV neutrinos in SN1987A. (3 The third is a comparison of GWs with different frequencies in the range [35 Hz, 250 Hz]. (4 The fourth is a comparison of EM waves with different energies in the range [1 keV, 10 MeV]. These last two comparisons lead to an even stronger limit, Δγ≲10−8. Our results highlight the potential of multi-messenger signals exploiting different emission channels to strengthen existing tests of the WEP.

  7. Model study of the impacts of future climate change on the hydrology of Ganges-Brahmaputra-Meghna (GBM) basin

    Science.gov (United States)

    Masood, M.; Yeh, P. J.-F.; Hanasaki, N.; Takeuchi, K.

    2014-06-01

    The intensity, duration, and geographic extent of floods in Bangladesh mostly depend on the combined influences of three river systems, Ganges, Brahmaputra and Meghna (GBM). In addition, climate change is likely to have significant effects on the hydrology and water resources of the GBM basins and might ultimately lead to more serious floods in Bangladesh. However, the assessment of climate change impacts on basin-scale hydrology by using well-constrained hydrologic modelling has rarely been conducted for GBM basins due to the lack of data for model calibration and validation. In this study, a macro-scale hydrologic model H08 has been applied regionally over the basin at a relatively fine grid resolution (10 km) by integrating the fine-resolution (~0.5 km) DEM data for accurate river networks delineation. The model has been calibrated via analyzing model parameter sensitivity and validated based on a long-term observed daily streamflow data. The impact of climate change on not only the runoff, but also the basin-scale hydrology including evapotranspiration, soil moisture and net radiation have been assessed in this study through three time-slice experiments; present-day (1979-2003), near-future (2015-2039) and far-future (2075-2099) periods. Results shows that, by the end of 21st century (a) the entire GBM basin is projected to be warmed by ~3°C (b) the changes of mean precipitation are projected to be +14.0, +10.4, and +15.2%, and the changes of mean runoff to be +14, +15, and +18% in the Brahmaputra, Ganges and Meghna basin respectively (c) evapotranspiration is predicted to increase significantly for the entire GBM basins (Brahmaputra: +14.4%, Ganges: +9.4%, Meghna: +8.8%) due to increased net radiation (Brahmaputra: +6%, Ganges: +5.9%, Meghna: +3.3%) as well as warmer air temperature. Changes of hydrologic variables will be larger in dry season (November-April) than that in wet season (May-October). Amongst three basins, Meghna shows the largest hydrological

  8. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

    Science.gov (United States)

    Schijns, Virgil E J C; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Chen, Thomas C; Mespouille, Pascal; Hantos, Peter; Glorieux, Philippe; Bota, Daniela A; Stathopoulos, Apostolos

    2015-05-28

    Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Neil Hayes, M.D., M.P.H., Explains TCGA Findings on GBM Subtypes - TCGA

    Science.gov (United States)

    New findings by researchers at UNC Lineberger Comprehensive Cancer Center suggest that the most common form of malignant brain cancer in adults, glioblastoma multiforme (GBM), is probably not a single disease but a set of diseases, each with a distinct underlying molecular disease process. The study was published by Cell Press in the January issue of the journal Cancer Cell and the researchers are part of the The Cancer Genome Atlas.

  10. Does age matter? Sexual event-level analysis of age-disparate sexual partners among gay, bisexual and other men who have sex with men (GBM) in Vancouver, Canada.

    Science.gov (United States)

    Closson, K; Lachowsky, N J; Cui, Z; Shurgold, S; Sereda, P; Rich, A; Moore, D M; Roth, E A; Hogg, R S

    2017-08-01

    To determine factors associated with age-disparate sexual partners among Vancouver gay, bisexual and other men who have sex with men (GBM). Sexually active GBM aged ≥16 years were recruited from February 2012 to February 2014. Participants self-completed a questionnaire on demographics, attitudes and sexual behaviour and substance use at last sexual event with five most recent partners. Two generalised linear mixed models identified factors associated with: (1) 'same-age' (referent), 'younger' or 'much-younger' and (2) 'same-age' (referent), 'older' or 'much-older' partners. Statistical interactions between age and HIV status were tested. Participants (n=719) were predominantly gay (85.1%), White (75.0%), HIV-negative/unknown status (72.9%) with median age of 33 years (Q1,Q3: 26,47). A minority of sexual events were reported with much-older/much-younger partners (13.7%). In the multivariable models, GBM reporting older partners were more likely to be Asian or Latino, have greater Escape Motivation scores, report their partner used erectile dysfunction drugs (EDDs) and have received something for sex; compared with condom-protected insertive anal sex, participants with older partners were more likely to report condomless insertive anal sex with a serodiscordant or unknown status partner or no insertive anal sex. GBM reporting older partners were less likely to be bisexual-identified, have given something for sex and report event-level alcohol and EDD use. GBM reporting younger partners were more likely to have annual incomes >$30 000 and have met their partner online. As per significant statistical interactions, age-disparate relations were more common for younger HIV-positive and older HIV-negative GBM. Differences among age-disparate partners highlight important targets for health promotion and future research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

    Directory of Open Access Journals (Sweden)

    Kistler Thomas

    2011-06-01

    Full Text Available Abstract Background Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA. Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. Case Presentation We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppresive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2, a novel autoantigen in patients with active small-vessel vasculitis (SVV. The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. Conclusion We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts.

  12. ANCA-GBM dot-blot : Evaluation of an assay in the differential diagnosis of patients presenting with rapidly progressive glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Damoiseaux, Jan; Roozendaal, Caroline; Limburg, Pieter C; Stegeman, Coen A; Tervaert, Jan Willem Cohen

    Rapidly progressive glomerulonephritis (RPGN) is characterized by rapid and progressive loss of renal function and the presence of crescentic glomerulonephritis (CGN). Early diagnosis and appropriate treatment is mandatory to prevent death and/or renal failure. We have evaluated an ANCA-GBM dot-blot

  13. GRAVITATIONAL-WAVE OBSERVATIONS MAY CONSTRAIN GAMMA-RAY BURST MODELS: THE CASE OF GW150914–GBM

    Energy Technology Data Exchange (ETDEWEB)

    Veres, P. [CSPAR, University of Alabama in Huntsville, 320 Sparkman Dr., Huntsville, AL 35805 (United States); Preece, R. D. [Dept. of Space Science, University of Alabama in Huntsville, 320 Sparkman Dr., Huntsville, AL 35805 (United States); Goldstein, A.; Connaughton, V. [Universities Space Research Association, 320 Sparkman Dr. Huntsville, AL 35806 (United States); Mészáros, P. [Dept. of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Burns, E., E-mail: peter.veres@uah.edu [Physics Dept., University of Alabama in Huntsville, 320 Sparkman Dr., Huntsville, AL 35805 (United States)

    2016-08-20

    The possible short gamma-ray burst (GRB) observed by Fermi /GBM in coincidence with the first gravitational-wave (GW) detection offers new ways to test GRB prompt emission models. GW observations provide previously inaccessible physical parameters for the black hole central engine such as its horizon radius and rotation parameter. Using a minimum jet launching radius from the Advanced LIGO measurement of GW 150914, we calculate photospheric and internal shock models and find that they are marginally inconsistent with the GBM data, but cannot be definitely ruled out. Dissipative photosphere models, however, have no problem explaining the observations. Based on the peak energy and the observed flux, we find that the external shock model gives a natural explanation, suggesting a low interstellar density (∼10{sup −3} cm{sup −3}) and a high Lorentz factor (∼2000). We only speculate on the exact nature of the system producing the gamma-rays, and study the parameter space of a generic Blandford–Znajek model. If future joint observations confirm the GW–short-GRB association we can provide similar but more detailed tests for prompt emission models.

  14. Epidermal growth factor receptor (EGFR mutation status and Rad51 determine the response of glioblastoma (GBM to multimodality therapy with cetuximab, temozolomide and radiation

    Directory of Open Access Journals (Sweden)

    Phyllis Rachelle Wachsberger

    2013-02-01

    Full Text Available Purpose: EGFR amplification and mutation (i.e., EGFRvIII are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolamide (TMZ and radiation therapy (RT Methods and Materials: In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR and the other overexpressing EGFRvIII (U87EGFRvIII. Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing, Conclusions: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.

  15. Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery.

    Science.gov (United States)

    Carlson, Brett L; Pokorny, Jenny L; Schroeder, Mark A; Sarkaria, Jann N

    2011-03-01

    Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important for advancement of basic and translational biology. One model that has gained wide acceptance in the neuro-oncology community is the primary xenograft model. This model entails the engraftment of patient tumor specimens into the flank of nude mice and subsequent serial passage of these tumors in the flank of mice. These tumors are then used to establish short-term explant cultures or intracranial xenografts. This unit describes detailed procedures for establishment, maintenance, and utilization of a primary GBM xenograft panel for the purpose of using them as tumor models for basic or translational studies.

  16. Testing the Isotropic Universe Using the Gamma-Ray Burst Data of Fermi/GBM

    Science.gov (United States)

    Řípa, Jakub; Shafieloo, Arman

    2017-12-01

    The sky distribution of gamma-ray bursts (GRBs) has been intensively studied by various groups for more than two decades. Most of these studies test the isotropy of GRBs based on their sky number density distribution. In this work, we propose an approach to test the isotropy of the universe through inspecting the isotropy of the properties of GRBs such as their duration, fluences, and peak fluxes at various energy bands and different timescales. We apply this method on the Fermi/Gamma-ray Burst Monitor (GBM) data sample containing 1591 GRBs. The most noticeable feature we found is near the Galactic coordinates l≈ 30^\\circ , b≈ 15^\\circ , and radius r≈ 20^\\circ {--}40^\\circ . The inferred probability for the occurrence of such an anisotropic signal (in a random isotropic sample) is derived to be less than a percent in some of the tests while the other tests give results consistent with isotropy. These are based on the comparison of the results from the real data with the randomly shuffled data samples. Considering the large number of statistics we used in this work (some of which are correlated with each other), we can anticipate that the detected feature could be a result of statistical fluctuations. Moreover, we noticed a considerably low number of GRBs in this particular patch, which might be due to some instrumentation or observational effects that can consequently affect our statistics through some systematics. Further investigation is highly desirable in order to clarify this result, e.g., utilizing a larger future Fermi/GBM data sample as well as data samples of other GRB missions and also looking for possible systematics.

  17. Food and nutrition security trends and challenges in the Ganges Brahmaputra Meghna (GBM delta

    Directory of Open Access Journals (Sweden)

    Arnout van Soesbergen

    2017-09-01

    Full Text Available The population of the Ganges Brahmaputra Meghna (GBM delta is highly vulnerable to food insecurity and malnutrition due to the specific environmental, climatic and human development factors affecting agricultural production and fisheries. To better understand the impacts of climate and environmental change on food security and nutrition in this delta, this study combines spatially explicit data from the 2007 and 2011 Bangladesh Demographic and Health Survey (BDHS with a standard satellite remotely sensed vegetation greenness index (Normalised Difference Vegetation Index, NDVI, used as a proxy for rice production. The strength of association between NDVI and child nutrition in this tropical mega-delta were tested, showing correlations between two widely used indicators of child malnutrition; stunting and wasting, and deviations from a 10 year mean NDVI (anomalies for rice crop growing seasons – regarded as critical to individual children’s early lives. For children surveyed in 2007 we found that the likelihood of being stunted decreased with increased NDVI as a measure of food production. Similarly, for children surveyed in 2011, the likelihood of being wasted reduced with increased NDVI. However, regression results for stunting in 2011 and wasting in 2007 were not statistically significant. Our findings suggest that NDVI can be regarded as indicative of climatic variability and periods of low food production but is only partly successful as an indicator of climate related impacts on child nutrition in the GBM delta. Furthermore, our study highlights some of the uncertainties and challenges with linking environmental indicators such as the NDVI with household survey data across spatial and temporal scales.

  18. Spectral evolution of GRBs with negative spectral lag using Fermi GBM observations

    Science.gov (United States)

    Chakrabarti, Arundhati; Chaudhury, Kishor; Sarkar, Samir K.; Bhadra, Arunava

    2018-06-01

    The positive spectral lag of Gamma Ray Bursts (GRBs) is often explained in terms of hard-to-soft spectral evolution of GRB pulses. While positive lags of GRBs is very common, there are few GRB pulses that exhibits negative spectral lags. In the present work we examine whether negative lags of GRBs also can be interpreted in terms of spectral evolution of GRB pulses or not. Using Fermi-GBM data, we identify two GRBs, GRB 090426C and GRB 150213A, with clean pulses that exhibit negative spectral lag. An indication of soft to hard transition has been noticed for the negative spectral lag events from the spectral evolution study. The implication of the present findings on the models of GRB spectral lags are discussed.

  19. Size of shell universe in light of Fermi GBM transient associated with GW150914

    Directory of Open Access Journals (Sweden)

    Merab Gogberashvili

    2016-12-01

    Full Text Available The possible burst occurred in location and temporal consistence with gravitational wave event GW150914, as reported by Fermi GBM, offers a new way of constraining models with extra dimensions. Using the time delay in arrival of the gamma ray transient observed by Fermi Gamma-ray Burst Monitor (GMB relative to the gravitational waves event triggered by the LIGO detectors we investigate the size of the spherical brane-universe expanding in multi-dimensional space–time. It is shown that a joint observation of gravitational waves in association with gamma ray burst can provide a very stringent bound on the spatial curvature of the brain.

  20. Size of shell universe in light of Fermi GBM transient associated with GW150914

    Energy Technology Data Exchange (ETDEWEB)

    Gogberashvili, Merab, E-mail: gogber@gmail.com [Department of Exact and Natural Sciences, Javakhishvili Tbilisi State University, Tbilisi 0179, Georgia (United States); Department of High Energy Physics, Andronikashvili Institute of Physics, Tbilisi 0177, Georgia (United States); Sakharov, Alexander S., E-mail: Alexandre.Sakharov@cern.ch [Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Physics Department, Manhattan College, 4513 Manhattan College Parkway, Riverdale, NY 10471 (United States); Experimental Physics Department, CERN, CH-1211 Genève 23 (Switzerland); Sarkisyan-Grinbaum, Edward K., E-mail: sedward@cern.ch [Experimental Physics Department, CERN, CH-1211 Genève 23 (Switzerland); Department of Physics, The University of Texas at Arlington, 502 Yates Street, Box 19059, Arlington, TX 76019 (United States)

    2016-12-10

    The possible burst occurred in location and temporal consistence with gravitational wave event GW150914, as reported by Fermi GBM, offers a new way of constraining models with extra dimensions. Using the time delay in arrival of the gamma ray transient observed by Fermi Gamma-ray Burst Monitor (GMB) relative to the gravitational waves event triggered by the LIGO detectors we investigate the size of the spherical brane-universe expanding in multi-dimensional space–time. It is shown that a joint observation of gravitational waves in association with gamma ray burst can provide a very stringent bound on the spatial curvature of the brain.

  1. The IPV-GBM scale: a new scale to measure intimate partner violence among gay and bisexual men.

    Science.gov (United States)

    Stephenson, Rob; Finneran, Catherine

    2013-01-01

    The paper describes the creation of a new scale to measure intimate partner violence (IPV) among gay and bisexual men. Seven focus group discussions were held with gay and bisexual men, focusing on defining intimate partner violence: 30 forms of IPV were identified. A venue-recruited sample of 912 gay and bisexual men was surveyed, examining definitional understanding and recent experiences of each of the 30 forms of IPV. Participants were also asked questions from the CDC definition of intimate partner violence and the short-form of the Conflicts Tactics Scale (CTS2S). Factor analysis of responses to the definitional questions was used to create the IPV-GBM scale, and the prevalence of intimate partner violence was compared with that identified by the CDC and CTS2S measures of intimate partner violence. A 23-item scale, with 5 unique domains, was created, with strong internal reliability (Cronbach Alpha >.90). The IPV-GBM scale mirrored both the CDC and CTS2S definitions of intimate partner violence, but contained additional domains such as controlling violence, monitoring behaviors, emotional violence, and HIV-related violence. The new scale identified a significantly higher prevalence of IPV than either of the more commonly used measures. The results presented here provide encouraging evidence for a new, more accurate measure of intimate partner violence among gay and bisexual men in the U.S.

  2. The IPV-GBM scale: a new scale to measure intimate partner violence among gay and bisexual men.

    Directory of Open Access Journals (Sweden)

    Rob Stephenson

    Full Text Available The paper describes the creation of a new scale to measure intimate partner violence (IPV among gay and bisexual men.Seven focus group discussions were held with gay and bisexual men, focusing on defining intimate partner violence: 30 forms of IPV were identified. A venue-recruited sample of 912 gay and bisexual men was surveyed, examining definitional understanding and recent experiences of each of the 30 forms of IPV. Participants were also asked questions from the CDC definition of intimate partner violence and the short-form of the Conflicts Tactics Scale (CTS2S. Factor analysis of responses to the definitional questions was used to create the IPV-GBM scale, and the prevalence of intimate partner violence was compared with that identified by the CDC and CTS2S measures of intimate partner violence.A 23-item scale, with 5 unique domains, was created, with strong internal reliability (Cronbach Alpha >.90. The IPV-GBM scale mirrored both the CDC and CTS2S definitions of intimate partner violence, but contained additional domains such as controlling violence, monitoring behaviors, emotional violence, and HIV-related violence. The new scale identified a significantly higher prevalence of IPV than either of the more commonly used measures.The results presented here provide encouraging evidence for a new, more accurate measure of intimate partner violence among gay and bisexual men in the U.S.

  3. SU-F-R-17: Advancing Glioblastoma Multiforme (GBM) Recurrence Detection with MRI Image Texture Feature Extraction and Machine Learning

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Ruan, D; Nguyen, D; Kaprealian, T; Chin, R; Sheng, K [UCLA School of Medicine, Los Angeles, CA (United States)

    2016-06-15

    Purpose: To test the potential of early Glioblastoma Multiforme (GBM) recurrence detection utilizing image texture pattern analysis in serial MR images post primary treatment intervention. Methods: MR image-sets of six time points prior to the confirmed recurrence diagnosis of a GBM patient were included in this study, with each time point containing T1 pre-contrast, T1 post-contrast, T2-Flair, and T2-TSE images. Eight Gray-level co-occurrence matrix (GLCM) texture features including Contrast, Correlation, Dissimilarity, Energy, Entropy, Homogeneity, Sum-Average, and Variance were calculated from all images, resulting in a total of 32 features at each time point. A confirmed recurrent volume was contoured, along with an adjacent non-recurrent region-of-interest (ROI) and both volumes were propagated to all prior time points via deformable image registration. A support vector machine (SVM) with radial-basis-function kernels was trained on the latest time point prior to the confirmed recurrence to construct a model for recurrence classification. The SVM model was then applied to all prior time points and the volumes classified as recurrence were obtained. Results: An increase in classified volume was observed over time as expected. The size of classified recurrence maintained at a stable level of approximately 0.1 cm{sup 3} up to 272 days prior to confirmation. Noticeable volume increase to 0.44 cm{sup 3} was demonstrated at 96 days prior, followed by significant increase to 1.57 cm{sup 3} at 42 days prior. Visualization of the classified volume shows the merging of recurrence-susceptible region as the volume change became noticeable. Conclusion: Image texture pattern analysis in serial MR images appears to be sensitive to detecting the recurrent GBM a long time before the recurrence is confirmed by a radiologist. The early detection may improve the efficacy of targeted intervention including radiosurgery. More patient cases will be included to create a generalizable

  4. Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab.

    Science.gov (United States)

    Nelson, Sarah J; Li, Yan; Lupo, Janine M; Olson, Marram; Crane, Jason C; Molinaro, Annette; Roy, Ritu; Clarke, Jennifer; Butowski, Nicholas; Prados, Michael; Cha, Soonmee; Chang, Susan M

    2016-10-01

    Interpretation of changes in the T1- and T2-weighted MR images from patients with newly diagnosed glioblastoma (GBM) treated with standard of care in conjunction with anti-angiogenic agents is complicated by pseudoprogression and pseudoresponse. The hypothesis being tested in this study was that 3D H-1 magnetic resonance spectroscopic imaging (MRSI) provides estimates of levels of choline, creatine, N-acetylaspartate (NAA), lactate and lipid that change in response to treatment and that metrics describing these characteristics are associated with survival. Thirty-one patients with newly diagnosed GBM and being treated with radiation therapy (RT), temozolomide, erlotinib and bevacizumab were recruited to receive serial MR scans that included 3-D lactate edited MRSI at baseline, mid-RT, post-RT and at specific follow-up time points. The data were processed to provide estimates of metrics representing changes in metabolite levels relative to normal appearing brain. Cox proportional hazards analysis was applied to examine the relationship of these parameters with progression free survival (PFS) and overall survival (OS). There were significant reductions in parameters that describe relative levels of choline to NAA and creatine, indicating that the treatment caused a decrease in tumor cellularity. Changes in the levels of lactate and lipid relative to the NAA from contralateral brain were consistent with vascular normalization. Metabolic parameters from the first serial follow-up scan were associated with PFS and OS, when accounting for age and extent of resection. Integrating metabolic parameters into the assessment of patients with newly diagnosed GBM receiving therapies that include anti-angiogenic agents may be helpful for tracking changes in tumor burden, resolving ambiguities in anatomic images caused by non-specific treatment effects and for predicting outcome.

  5. CADrx for GBM Brain Tumors: Predicting Treatment Response from Changes in Diffusion-Weighted MRI

    Directory of Open Access Journals (Sweden)

    Matthew S. Brown

    2009-11-01

    Full Text Available The goal of this study was to develop a computer-aided therapeutic response (CADrx system for early prediction of drug treatment response for glioblastoma multiforme (GBM brain tumors with diffusion weighted (DW MR images. In conventional Macdonald assessment, tumor response is assessed nine weeks or more post-treatment. However, we will investigate the ability of DW-MRI to assess response earlier, at five weeks post treatment. The apparent diffusion coefficient (ADC map, calculated from DW images, has been shown to reveal changes in the tumor’s microenvironment preceding morphologic tumor changes. ADC values in treated brain tumors could theoretically both increase due to the cell kill (and thus reduced cell density and decrease due to inhibition of edema. In this study, we investigated the effectiveness of features that quantify changes from pre- and post-treatment tumor ADC histograms to detect treatment response. There are three parts to this study: first, tumor regions were segmented on T1w contrast enhanced images by Otsu’s thresholding method, and mapped from T1w images onto ADC images by a 3D region of interest (ROI mapping tool using DICOM header information; second, ADC histograms of the tumor region were extracted from both pre- and five weeks post-treatment scans, and fitted by a two-component Gaussian mixture model (GMM. The GMM features as well as standard histogram-based features were extracted. Finally, supervised machine learning techniques were applied for classification of responders or non-responders. The approach was evaluated with a dataset of 85 patients with GBM under chemotherapy, in which 39 responded and 46 did not, based on tumor volume reduction. We compared adaBoost, random forest and support vector machine classification algorithms, using ten-fold cross validation, resulting in the best accuracy of 69.41% and the corresponding area under the curve (Az of 0.70.

  6. Role of extent of resection on quality of life in patients with newly diagnosed GBM.

    Science.gov (United States)

    Choudry, Usama Khalid; Shaikh, Huzaifa Ismail; Nisar, Areeba; Khan, Saad Akhtar; Shamim, Muhammad Shahzad

    2018-01-01

    Glioblastomas known for their adverse outcomes are most reportedly managed by surgical resection. Studies on the impact of (Extent of Resection) EOR against Quality of Life (QOL) are very limited. We have collected data from recent studies in this review to extract a general consensus among the neurosurgeons regarding the EOR. Key parameters like functional independence, neurocognitive improvements and global health status have been explored in the context of QOL. The currently available data suggests that an increased EOR may help improve QOL in GBM patients. With the help of recent advancements it may be possible to attain a better extent of resection while operating on GBMs.

  7. TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

    International Nuclear Information System (INIS)

    Wang, Chao; Cao, Shouqiang; Yan, Ying; Ying, Qiao; Jiang, Tao; Xu, Ke; Wu, Anhua

    2010-01-01

    Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy

  8. Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG

    International Nuclear Information System (INIS)

    Belloli, Sara; Brioschi, Andrea; Politi, Letterio Salvatore; Ronchetti, Francesca; Calderoni, Sara; Raccagni, Isabella; Pagani, Antonella; Monterisi, Cristina; Zenga, Francesco; Zara, Gianpaolo; Fazio, Ferruccio; Mauro, Alessandro

    2013-01-01

    Introduction: The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods: Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [ 18 F]FDG- and [ 18 F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results: Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [ 18 F]FAZA and high-glucose metabolism regions recognized with [ 18 F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [ 18 F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [ 18 F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy. Conclusions: In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression

  9. The Problem with Briefs, in Brief

    Science.gov (United States)

    Conaway, Carrie L.

    2013-01-01

    Policy briefs written by academics--the kind typically published in "Education Finance and Policy"--should be a crucial source of information for policy makers. Yet too frequently these briefs fail to garner the consideration they deserve. Their authors are too focused on the potential objections of their fellow academics, who are…

  10. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Directory of Open Access Journals (Sweden)

    Nicolas M Bertagnolli

    Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  11. BBB disruption with unfocused ultrasound alone-A paradigm shift

    Science.gov (United States)

    Kyle, Al

    2012-10-01

    One paradigm for ultrasound-enabled blood brain barrier disruption uses image guided focused ultrasound and preformed microbubble agents to enable drug delivery to the brain. We propose an alternative approach: unguided, unfocused ultrasound with no adjunctive agent. Compared with the focused approach, the proposed method affects a larger region of the brain, and is aimed at treatment of regional neurological disease including glioblastoma multiforme (GBM). Avoidance of image guidance and focusing reduces cost for equipment and staff training. Avoidance of adjunctive agents also lowers cost and is enabled by a longer exposure time. Since 2004, our group has worked with two animal models, three investigators in four laboratories to safely deliver five compounds, increasing the concentration of large molecule markers in brain tissue two fold or more. Safety and effectiveness data for four studies have been presented at the Ultrasound Industry Association meetings in 2007 and 2010. This paper describes new safety and effectiveness results for a fifth study. We present evidence of delivery of large molecules - including Avastin-to the brains of a large animal model correlated with acoustic pressure, and summarize the advantages and disadvantages of this novel approach.

  12. Gbm.auto: A software tool to simplify spatial modelling and Marine Protected Area planning

    Science.gov (United States)

    Officer, Rick; Clarke, Maurice; Reid, David G.; Brophy, Deirdre

    2017-01-01

    Boosted Regression Trees. Excellent for data-poor spatial management but hard to use Marine resource managers and scientists often advocate spatial approaches to manage data-poor species. Existing spatial prediction and management techniques are either insufficiently robust, struggle with sparse input data, or make suboptimal use of multiple explanatory variables. Boosted Regression Trees feature excellent performance and are well suited to modelling the distribution of data-limited species, but are extremely complicated and time-consuming to learn and use, hindering access for a wide potential user base and therefore limiting uptake and usage. BRTs automated and simplified for accessible general use with rich feature set We have built a software suite in R which integrates pre-existing functions with new tailor-made functions to automate the processing and predictive mapping of species abundance data: by automating and greatly simplifying Boosted Regression Tree spatial modelling, the gbm.auto R package suite makes this powerful statistical modelling technique more accessible to potential users in the ecological and modelling communities. The package and its documentation allow the user to generate maps of predicted abundance, visualise the representativeness of those abundance maps and to plot the relative influence of explanatory variables and their relationship to the response variables. Databases of the processed model objects and a report explaining all the steps taken within the model are also generated. The package includes a previously unavailable Decision Support Tool which combines estimated escapement biomass (the percentage of an exploited population which must be retained each year to conserve it) with the predicted abundance maps to generate maps showing the location and size of habitat that should be protected to conserve the target stocks (candidate MPAs), based on stakeholder priorities, such as the minimisation of fishing effort displacement. Gbm

  13. Lahore general hospital protocol for treatment of neovascular glaucoma caused by retinal disease

    International Nuclear Information System (INIS)

    Khaqan, H.A.; Haider, S.A.

    2013-01-01

    To evaluate efficacy of LGH (Lahore General Hospital) protocol for treatment of neovascular glaucoma caused by retinal diseases. Material and Methods: This case series was performed on 9 consecutive eyes of nine patients with uncontrolled neovascular glaucoma at Department of Ophthalmology, Unit II, Lahore General Hospital/PGMI, Lahore. All nine patients completed six months follow up. Among them 6 patients were having PDR (proliferative diabetic retinopathy) and 3 patients having CRVO (central retinal vein occlusion). LGH protocol for treatment of neovascular glaucoma was: To give intravitreal injection of avastin and then PRP (Pan Retinal Photocoagulation) or Trabeculectomy with MMC (Mitomycin C), if PRP and intravitreal avastin fails to control the intra ocular-pressure (IOP). Results: Three patients had IOP control after intravitreal injection of avastin and PRP, 5 patients had uncontrolled IOP after intravitreal avastin and two sessions of PRP, so they under went trabeculectomy with MMC. One patient had uncontrolled IOP despite of full treatment protocol. All other 8 patients IOP remained stable for six months. Conclusion: Significant decrease in intraocular pressure was achieved after observing LGH protocol for treatment of NVG (Neovascular Glaucoma) caused by retinal diseases. (author)

  14. Simulation of glioblastoma multiforme (GBM) tumor cells using ising model on the Creutz Cellular Automaton

    Science.gov (United States)

    Züleyha, Artuç; Ziya, Merdan; Selçuk, Yeşiltaş; Kemal, Öztürk M.; Mesut, Tez

    2017-11-01

    Computational models for tumors have difficulties due to complexity of tumor nature and capacities of computational tools, however, these models provide visions to understand interactions between tumor and its micro environment. Moreover computational models have potential to develop strategies for individualized treatments for cancer. To observe a solid brain tumor, glioblastoma multiforme (GBM), we present a two dimensional Ising Model applied on Creutz cellular automaton (CCA). The aim of this study is to analyze avascular spherical solid tumor growth, considering transitions between non tumor cells and cancer cells are like phase transitions in physical system. Ising model on CCA algorithm provides a deterministic approach with discrete time steps and local interactions in position space to view tumor growth as a function of time. Our simulation results are given for fixed tumor radius and they are compatible with theoretical and clinic data.

  15. Restriction spectrum imaging of bevacizumab-related necrosis in a patient with GBM

    Directory of Open Access Journals (Sweden)

    Nikdokht eFarid

    2013-09-01

    Full Text Available Importance:With the increasing use of antiangiogenic agents in the treatment of high grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations:We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI, an advanced diffusion-weighted imaging (DWI technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.Conclusions and Relevance:Our report increases the number of pathologically-proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

  16. Inclusive Briefing and User Involvement

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2011-01-01

    Briefing is not just about specifying needs as requirements but also about evaluating how well design proposals fulfil needs and aspirations. Furthermore, briefing is not only about building design. Briefing starts at the preproject stage to create a basis for the project decision and can include...... by top management. The article describes the briefing processes and the methods for user involvement, identifies problem areas and points out possible improvements. The author was actively involved in the project as deputy project director, with responsibility for the briefing process, and is now...... includes a literature study on briefing and user involvement in building projects, and presents a case study of a major building project of a new headquarters and media centre for the Danish Broadcasting Corporation in Copenhagen. The building project was actively used as part of a corporate change process...

  17. Dextrose-mediated aggregation of therapeutic monoclonal antibodies in human plasma: Implication of isoelectric precipitation of complement proteins.

    Science.gov (United States)

    Luo, Shen; Zhang, Baolin

    2015-01-01

    Many therapeutic monoclonal antibodies (mAbs) are clinically administered through intravenous infusion after mixing with a diluent, e.g., saline, 5% dextrose. Such a clinical setting increases the likelihood of interactions among mAb molecules, diluent, and plasma components, which may adversely affect product safety and efficacy. Avastin® (bevacizumab) and Herceptin® (trastuzumab), but not Remicade® (infliximab), were shown to undergo rapid aggregation upon dilution into 5% dextrose when mixed with human plasma in vitro; however, the biochemical pathways leading to the aggregation were not clearly defined. Here, we show that dextrose-mediated aggregation of Avastin or Herceptin in plasma involves isoelectric precipitation of complement proteins. Using mass spectrometry, we found that dextrose-induced insoluble aggregates were composed of mAb itself and multiple abundant plasma proteins, namely complement proteins C3, C4, factor H, fibronectin, and apolipoprotein. These plasma proteins, which are characterized by an isoelectronic point of 5.5-6.7, lost solubility at the resulting pH in the mixture with formulated Avastin (pH 6.2) and Herceptin (pH 6.0). Notably, switching formulation buffers for Avastin (pH 6.2) and Remicade (pH 7.2) reversed their aggregation profiles. Avastin formed little, if any, insoluble aggregates in dextrose-plasma upon raising the buffer pH to 7.2 or above. Furthermore, dextrose induced pH-dependent precipitation of plasma proteins, with massive insoluble aggregates being detected at pH 6.5-6.8. These data show that isoelectric precipitation of complement proteins is a prerequisite of dextrose-induced aggregation of mAb in human plasma. This finding highlights the importance of assessing the compatibility of a therapeutic mAb with diluent and human plasma during product development.

  18. Usability Briefing for hospital design

    DEFF Research Database (Denmark)

    Fronczek-Munter, Aneta

    This PhD thesis is a contribution to an ongoing debate in Denmark about improving the building design processes of complex buildings, especially in relation to the current hospital developments. It provides knowledge about capturing user needs and defines the process model for usability briefing...... and evaluations, can be fed into briefing and design processes. This PhD thesis proposes methods for usability briefing.Usability is a concept similar to functionality, but usability depends on: subjective view of users, context, culture, situation and experience. Understanding usability is achieved by involving...... users. This PhD thesis extends the research in usability of buildings to include all building design phases, therefore not only proposes usability evaluations, but also defines usability briefing. Briefing, also called architectural programming, is usually understood as one of the first phases...

  19. TU-CD-BRB-04: Automated Radiomic Features Complement the Prognostic Value of VASARI in the TCGA-GBM Dataset

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez, E Rios [Dana-Farber Cancer Institute | Harvard Medical School, Boston, MA (United States); Narayan, V [Dana-Farber Cancer Institute, Brigham and Womens Hospital, Harvard Medic, Boston, MA (United States); Grossmann, P [Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA (United States); Dunn, W; Gutman, D [Emory University School of Medicine, Atlanta, GA (United States); Aerts, H [Dana-Farber/Brigham Womens Cancer Center, Boston, MA (United States)

    2015-06-15

    Purpose: To compare the complementary prognostic value of automated Radiomic features to that of radiologist-annotated VASARI features in TCGA-GBM MRI dataset. Methods: For 96 GBM patients, pre-operative MRI images were obtained from The Cancer Imaging Archive. The abnormal tumor bulks were manually defined on post-contrast T1w images. The contrast-enhancing and necrotic regions were segmented using FAST. From these sub-volumes and the total abnormal tumor bulk, a set of Radiomic features quantifying phenotypic differences based on the tumor intensity, shape and texture, were extracted from the post-contrast T1w images. Minimum-redundancy-maximum-relevance (MRMR) was used to identify the most informative Radiomic, VASARI and combined Radiomic-VASARI features in 70% of the dataset (training-set). Multivariate Cox-proportional hazards models were evaluated in 30% of the dataset (validation-set) using the C-index for OS. A bootstrap procedure was used to assess significance while comparing the C-Indices of the different models. Results: Overall, the Radiomic features showed a moderate correlation with the radiologist-annotated VASARI features (r = −0.37 – 0.49); however that correlation was stronger for the Tumor Diameter and Proportion of Necrosis VASARI features (r = −0.71 – 0.69). After MRMR feature selection, the best-performing Radiomic, VASARI, and Radiomic-VASARI Cox-PH models showed a validation C-index of 0.56 (p = NS), 0.58 (p = NS) and 0.65 (p = 0.01), respectively. The combined Radiomic-VASARI model C-index was significantly higher than that obtained from either the Radiomic or VASARI model alone (p = <0.001). Conclusion: Quantitative volumetric and textural Radiomic features complement the qualitative and semi-quantitative annotated VASARI feature set. The prognostic value of informative qualitative VASARI features such as Eloquent Brain and Multifocality is increased with the addition of quantitative volumetric and textural features from the

  20. Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Tan

    2017-01-01

    Full Text Available Intravitreal bevacizumab (Avastin use in preterm infants with retinopathy of prematurity is associated with severe neurological disabilities, suggesting vascular leakage. We examined the hypothesis that intermittent hypoxia (IH potentiates intravitreal Avastin leakage. Neonatal rats at birth were exposed to IH from birth (P0–P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg was injected intravitreally into the left eye. Animals were placed in room air (RA until P23 or P45 for recovery (IHR. Hyperoxia-exposed and RA littermates served as oxygen controls, and equivalent volume saline served as the placebo controls. At P23 and P45 ocular angiogenesis, retinal pathology and ocular and systemic biomarkers of angiogenesis were examined. Retinal flatmounts showed poor peripheral vascularization in Avastin-treated and fellow eyes at P23, with numerous punctate hemorrhages and dilated, tortuous vessels with anastomoses at P45 in the rats exposed to IH. These adverse effects were associated with robust increases in systemic VEGF and in both treated and untreated fellow eyes. Histological analysis showed severe damage in the inner plexiform and inner nuclear layers. Exposure of IH/IHR-induced injured retinal microvasculature to anti-VEGF substances can result in vascular leakage and adverse effects in the developing neonate.

  1. Characteristics of team briefings in gynecological surgery.

    Science.gov (United States)

    Forsyth, Katherine L; Hildebrand, Emily A; Hallbeck, M Susan; Branaghan, Russell J; Blocker, Renaldo C

    2018-02-24

    Preoperative briefings have been proven beneficial for improving team performance in the operating room. However, there has been minimal research regarding team briefings in specific surgical domains. As part of a larger project to develop a briefing structure for gynecological surgery, the study aimed to better understand the current state of pre-operative team briefings in one department of an academic hospital. Twenty-four team briefings were observed and video recorded. Communication was analyzed and social network metrics were created based on the team member verbal interactions. Introductions occurred in only 25% of the briefings. Network analysis revealed that average team briefings exhibited a hierarchical structure of communication, with the surgeon speaking the most frequently. The average network for resident-led briefings displayed a non-hierarchical structure with all team members communicating with the resident. Briefings conducted without a standardized protocol can produce variable communication between the role leading and the team members present. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Testing the anisotropy in the angular distribution of Fermi/GBM gamma-ray bursts

    Science.gov (United States)

    Tarnopolski, M.

    2017-12-01

    Gamma-ray bursts (GRBs) were confirmed to be of extragalactic origin due to their isotropic angular distribution, combined with the fact that they exhibited an intensity distribution that deviated strongly from the -3/2 power law. This finding was later confirmed with the first redshift, equal to at least z = 0.835, measured for GRB970508. Despite this result, the data from CGRO/BATSE and Swift/BAT indicate that long GRBs are indeed distributed isotropically, but the distribution of short GRBs is anisotropic. Fermi/GBM has detected 1669 GRBs up to date, and their sky distribution is examined in this paper. A number of statistical tests are applied: nearest neighbour analysis, fractal dimension, dipole and quadrupole moments of the distribution function decomposed into spherical harmonics, binomial test and the two-point angular correlation function. Monte Carlo benchmark testing of each test is performed in order to evaluate its reliability. It is found that short GRBs are distributed anisotropically in the sky, and long ones have an isotropic distribution. The probability that these results are not a chance occurrence is equal to at least 99.98 per cent and 30.68 per cent for short and long GRBs, respectively. The cosmological context of this finding and its relation to large-scale structures is discussed.

  3. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

    Directory of Open Access Journals (Sweden)

    Garcia Juan L

    2010-08-01

    Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

  4. Sustainable Markets Investment Briefings: Overview

    Energy Technology Data Exchange (ETDEWEB)

    Cotula, Lorenzo

    2007-08-15

    This is the first of a series of briefings which discuss the sustainable development issues raised by legal arrangements for the protection of foreign investment. The briefings are based on legal research by IIED and its partners. The goal is to provide accessible but accurate information for human rights, development and environmental organisations working on issues raised by foreign investment in low- and middle-income countries. Briefing 1 provides a general overview of key issues.

  5. Performance-Based Funding Brief

    Science.gov (United States)

    Washington Higher Education Coordinating Board, 2011

    2011-01-01

    A number of states have made progress in implementing performance-based funding (PFB) and accountability. This policy brief summarizes main features of performance-based funding systems in three states: Tennessee, Ohio, and Indiana. The brief also identifies key issues that states considering performance-based funding must address, as well as…

  6. Professional Development. Issue Brief

    Science.gov (United States)

    Keleher, Julia

    2017-01-01

    In this professional development research brief, the author sets forth the overarching considerations that should be kept in mind when conceptualizing professional development for educators working with neglected or delinquent youth (N or D). The brief begins by defining professional development and demonstrating why it is a critical support for…

  7. Management of cataract with macular oedema due to diabetes mellitus Type-II and hypertension with grid laser prior to surgery and intra-vitreal bevacizumab (avastin) peroperatively

    International Nuclear Information System (INIS)

    Wahab, S.; Ahmed, J.

    2010-01-01

    To study the visual outcome in patients subjected to cataract extraction with prior grid laser and intraoperative intravitreal bevacizumab injection. Methods: This prospective case series comprised of 38 patients subjected to phacoemulsification and in the bag intraocular lens implantation at Al-Noor Eye Hospital and Sindh Govt Lyari General Hospital Karachi from January 2007 to December 2008. All the patients had prior macular grid treatment and intra-operative injection of intra-vitreal Avastin. Diabetes mellitus duration, preoperative glycosylated haemoglobin (HbA1c) level and other systemic and local complications of diabetes were recorded. The patients were clinically assessed with bio microscopic examination preoperatively, and postoperatively on day 1, week 1, and in months 1, 2, 3 and 6 respectively. Visual acuity and state of macular oedema was clinically assessed and documented. Results: Out of thirty-eight patients, eighteen were males and 20 were females. Mean duration of diabetes was 9.92 +- 5.5 years (Range 4-16) while that of hypertension was 7.87 +- 3.66 years (Range = 2-15). HbA1c level was 8.36% +- 1.93% (range 6.3 - 12.3). Thirty-one (81.5%) patients had HbA1c level 8.0% or above indicating a poor control. At 6 months of follow up best corrected distant visual acuity of 6/6 to 6/9 was achieved in 23(60.5 %), 6/12 in 11(28.9%) and 6/24 in 4(10.5%) cases while best corrected near acuity of N/6 was achieved in 22(57.8%) N/8 in 12(31.4%) and N/12 in 4(10.5%) cases. At 6 months follow up visual acuity declined in two cases because of uncontrolled diabetes and hypertension. Conclusion: Cataract surgery in diabetic patients with macular oedema and hypertension has a good visual outcome if prior macular grid laser is performed and intra-vitreal anti VEGF is injected during surgery. (author)

  8. Cybernetics of Brief Family Therapy.

    Science.gov (United States)

    Keeney, Bradford P.; Ross, Jeffrey M.

    1983-01-01

    Presents a cybernetic view of brief family therapy. Includes a historical discussion of the key ideas underlying brief family therapy, a cybernetic model of therapeutic change, and a clinical case for exemplification. (Author/JAC)

  9. Management briefs 2/92

    International Nuclear Information System (INIS)

    1993-01-01

    Brief reports inform about research activities and meetings. The German industry's alarm at the introduction of a carbon dioxide tax is expressed in an article, and a short note refers to the disquiet on the part of the natural gas industry. A brief account is given of the continuation and expansion of nuclear power generation in Japan. (DG) [de

  10. Recent developments: Industry briefs

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Recent nuclear industry briefs are presented. These briefs include: Swiss voters reject phaseout; EdF confirms order for Civaux 1; NDP surprise victor in Ontario; Czechoslovakia joins Foratom; Poland abandons Zarnowiec; Cogema's UP3 facility operationa; Wismut to clsoe mining operations; court rules in favor of US government in Yucca Mountain waste site; Italian government ratifies ENEL reactor shutdowns; and Seabrook enters commercial operation

  11. What does "brief" mean? A theoretical critique of the concept of brief therapy from a psychoanalytic viewpoint.

    Science.gov (United States)

    Migone, Paolo

    2014-08-01

    The concept of "brief therapy" contains internal contradictions. The techniques suggested by brief therapists are the same techniques that have been discussed historically in debates on theory of technique, both within and without psychoanalysis (e.g., the experiential factor at the center of the Freud-Ferenczi confrontation is also an important aspect of Gestalt therapy). A time limit is the only operational criterion that allows a rigorous definition of brief therapy; without this criterion it is impossible to discriminate between "brief" and simply "good" therapies (i.e., those in which patients are successfully treated in a short time). An important question is why, with a given patient, a therapist should decide, a priori, to terminate a treatment within a set time. Two clinical examples are presented, illustrating the usefulness of Eissler's concept of parameters as a heuristic framework to identify the potentially defensive nature of both "brief" and "long-term" therapy. © 2014 by the American Psychoanalytic Association.

  12. Brief communication

    Indian Academy of Sciences (India)

    2011-03-14

    Mar 14, 2011 ... 1Department of Crop, Soil and Environmental Sciences, 2Department of Horticulture, University of Arkansas, ... controlled by the soybean heat-shock promoter is an effective tool for conditional removal ... Brief communication ...

  13. 6 CFR 13.36 - Post-hearing briefs.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Post-hearing briefs. 13.36 Section 13.36 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.36 Post-hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event...

  14. Brief communication

    Indian Academy of Sciences (India)

    2013-11-05

    Nov 5, 2013 ... Brief communication. Published ... showed longer FIDs in response to a human looking at them than to a human not looking at them (Burger et al. 1992). ..... Rivas JA and Burghardt GM 2001 Understanding sexual size dimor-.

  15. Sustainable Markets Investment Briefings: Investment Treaties

    Energy Technology Data Exchange (ETDEWEB)

    Cotula, Lorenzo

    2007-08-15

    This is the second of a series of briefings which discuss the sustainable development issues raised by legal arrangements for the protection of foreign investment. The briefings are based on legal research by IIED and its partners. The goal is to provide accessible but accurate information for human rights, development and environmental organisations working on issues raised by foreign investment in low- and middle-income countries. Briefing 2 explains how investment treaties between states work to protect and promote foreign investment.

  16. 39 CFR 3001.34 - Briefs.

    Science.gov (United States)

    2010-07-01

    ..., due regard shall be given to the nature of the proceeding, the complexity and importance of the issues... brief at the same time. In cases where, because of the nature of the issues and the record or the... any other brief, pleading or document. (d) Excerpts from the record. Testimony and exhibits shall not...

  17. Graph analysis of cell clusters forming vascular networks

    Science.gov (United States)

    Alves, A. P.; Mesquita, O. N.; Gómez-Gardeñes, J.; Agero, U.

    2018-03-01

    This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks.

  18. Recent developments: Industry briefs

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The January 1992 Industry Briefs includes brief articles on: (1) the startup of Chinese and Indian nuclear units, (2) agreements between China and Pakistan for the construction of a nuclear unit, (3) international safeguards agreements, (4) restart of a nuclear unit in Armenia, (5) closure of a German nuclear waste site, (6) restructuring of the Hungarian state-owned utility MVMT, (7) requests for bids for Wolsong Units 3 and 4, (8) signing of the European Energy charter, (9) continued operation of the MAGNOX reactors, and (10) changing Canadian requirements on uranium

  19. Our Ocean Wealth - Background Briefing Documents: Part II: Sectoral Briefs

    OpenAIRE

    Department of Agriculture, Food and the Marine

    2012-01-01

    This briefing document provides a profile our marine sectors including an overview of current Government plans and policies in place (seafood, seaweed, shipping and maritime transport, renewable and non-renewable energy, marine ICT and biotechnology).

  20. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

    Directory of Open Access Journals (Sweden)

    Anjali Shiras

    2003-11-01

    Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

  1. 45 CFR 99.31 - Posthearing briefs.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Posthearing briefs. 99.31 Section 99.31 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND DEVELOPMENT FUND Posthearing Procedures, Decisions § 99.31 Posthearing briefs. The...

  2. A review of obesity-themed policy briefs.

    Science.gov (United States)

    Dodson, Elizabeth A; Eyler, Amy A; Chalifour, Stephanie; Wintrode, Christopher G

    2012-09-01

    Policy approaches are one of the most promising population-based means of addressing the epidemic of obesity in the U.S., especially as they create supportive environments for healthy living. Policy briefs can be an effective means of disseminating research information to inform obesity prevention efforts; however, they are often ineffective because of length, density, and inaccessibility. The purposes of this project were to identify a collection of obesity-related policy briefs, analyze the content, and make recommendations for model policy briefs. In 2010, online searching strategies were developed with criteria that included a primary topical focus on obesity, written between 2000 and 2010, targeting any population age group, including a policy-change message, and being readily available online. The research team developed a coding tool and used it to analyze briefs. A subsample of the briefs was used for further analysis on dissemination. Analyses were conducted on 100 briefs. Most (72%) were developed between 2005 and 2010; the average length was five pages. The majority had no tables, few figures, and only 36% included photos. The average reading level was high. A lack of monitoring or evaluating dissemination efforts prevailed. Policy briefs represent an effective, often-preferred, potent tool for public health practitioners and researchers to communicate information to policymakers. Recommendations include presenting information clearly, using a concise format, including design elements, noting reference and contact information, employing active and targeted dissemination efforts, and conducting evaluation. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Paradox of Migration in Kolkata: A Megacity in GBM Delta

    Science.gov (United States)

    Das, S.; Hazra, S.; Ghosh, T.

    2015-12-01

    Contrary to other coastal cities (Mumbai, Chennai, Bhubaneswar etc.) in India, Kolkata, the largest city of India until 1990, has been showing a persistent trend of out-migration over the last decade. The situation is more paradoxical when compared to Dhaka in Bangladesh, the other coastal city in Ganga-Brahmaputra-Meghna (GBM) delta. Exacerbating impacts of Climate Change like accelerated sea level rise, impact of cyclones, rising temperature and high rainfall events and waterlogging, vis-à-vis the density of poor population in slums, Kolkata has been assessed as one of the most vulnerable cities of the world. However, Kolkata has long been a preferred destination for migrants for its port based economy, existence of industrial belt with labour intensive industries. The city and its surrounding districts attracted a massive influx of trans-border migrants when India and Bangladesh gained Independence in 1947 and 1971 respectively. The paper attempts to explore reasons behind the present trend of depopulation in the erstwhile preferred migration destination. This paper distinguishes between 'Kolkata City' (census district) with 4.5 million residents and 'Kolkata Megacity' which encompasses also the peri-urban areas and home to almost 14.1 million people according to Census 2011. Analysing migration as an ongoing research activity under DECCMA project, an overall 'in-migration' pattern can be deciphered in Kolkata 'megacity'. On the contrary, the Kolkata 'city' located right in the heart of the megacity exhibits negative net migration (-5.11%) i.e. high 'out-migration'. Plausible causes can be movement of people from Kolkata 'city' to peri-urban areas and satellite towns (urban to urban migration) probably due to closure of labour intensive industries, comparatively lower land prices, availability of space and accommodation, lower costs of living, development of different modes of commutation and communication. Further growth of population in the Kolkata Megacity

  4. Boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM), using the epithermal neutron beam at the Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Chadha, Manjeet; Capala, Jacek; Coderre, Jeffrey A.; Elowitz, Eric H.; Joel, Darrel D.; Hungyuan, B. Liu; Slatkin, Daniel N.; Chanana, Arjun D.

    1996-01-01

    Objective: BNCT is a binary treatment modality based on the nuclear reactions that occur when boron ( 10 B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objective of the Phase I/II trial was to evaluate BPA-fructose (BPA-F) as a boron delivery agent for GBM and to study the feasibility and safety of a single-fraction of BNCT. Materials and Methods: The trial design required i) a BPA-F biodistribution study performed at the time of craniotomy; and ii) BNCT within 4 weeks of the craniotomy. From September 94 to July 95, 10 patients with biopsy proven GBM were treated. All but 1 patient underwent a biodistribution study receiving IV BPA-F at the time of craniotomy. Multiple tissue samples and concurrent blood and urine samples were collected for evaluation of the boron concentration and clearance kinetics. For BNCT all patients received 250 mg/kgm of BPA-F (IV infusion over 2 hrs) followed by neutron irradiation. The blood 10 B concentration during irradiation was used to calculate the time of neutron exposure. The 3D treatment planning was done using the BNCT treatment planning software developed at the Idaho National Engineering Laboratory. The BNCT dose is expressed as the sum of the physical dose components corrected for both the RBE and the 10 B localization factor with the unit Gy-Eq. The photon-equivalent dose, where the thermal neutron fluence reaches a maximum, is the peak-dose equivalent. A single-fraction of BNCT was delivered prescribing 10.5 Gy-Eq (9 patients) and 13.8 Gy-Eq (1 patient) as the peak dose-equivalent to the normal brain. The peak dose rate was kept below 27 cGy-Eq/min. Results: Biodistribution data: The maximum blood 10 B concentration was observed at the end of the infusion and scaled as a linear function of the administered dose. The 10 B concentration in the scalp and in the GBM tissue was higher than in blood by 1.5 x and at least 3.5 x

  5. 37 CFR 2.128 - Briefs at final hearing.

    Science.gov (United States)

    2010-07-01

    ... brief, and the rebuttal brief by the parties. (3) When a party in the position of plaintiff fails to.... If plaintiff fails to file a response to the order, or files a response indicating that he has lost... index of cited cases. Without prior leave of the Trademark Trial and Appeal Board, a main brief on the...

  6. Continuous Briefing and User Participation in Building Projects

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2006-01-01

    and the methods for user participation, identifies problem areas and point out possible improvements. The author has been actively involved in the project as deputy project director with re-sponsibility for the briefing process until spring 2005 and is now a researcher.......Briefing is not just about specifying needs as requirements but also about evaluating how well design pro-posals fulfill the needs and aspirations. Furthermore, briefing is not only about building design. Briefing starts at the pre-project stage to create a basis for the project decision...... into the building is required. A building project is often part of a change process of the organisation that is going to occupy the building, and this change process should be management carefully to reach a successful result. An important aspect of briefing is to manage the par-ticipation of the coming users...

  7. Gas-fired power. IEA ETSAP technology brief E02

    Energy Technology Data Exchange (ETDEWEB)

    Seebregts, A.J. [Energy research Centre of the Netherlands (Netherlands)], E-mail: seebregts@ecn.nl

    2010-04-15

    This technology brief on gas-fired power is part of a series produced by the IEA called the energy technology data source (E-Tech-DS). The E-Tech-DS series consists of a number of 5-10 page technology briefs similar to the IEA Energy Technology Essentials. Based on the data collected for the models that the Energy Technology Systems Analysis Programme (ETSAP) is known for, ETSAP also prepares technology briefs, called E-TechDS. The E-TechDS briefs are standardized presentations of basic information (process, status, performance, costs, potential, and barriers) for key energy technology clusters. Each brief includes an overview of the technology, charts and graphs, and a summary data table, and usually ending with some key references and further information. The E TechDS briefs are intended to offer essential, reliable and quantitative information to energy analysts, experts, policymakers, investors and media from both developed and developing countries. This specific brief focuses on the state of combined-cycle gas turbines (CCGT). CCGT's have become the technology of choice for new gas-fired power plants since the 1990's.

  8. Sustainable Markets Investment Briefings: Foreign investment contracts

    Energy Technology Data Exchange (ETDEWEB)

    Cotula, Lorenzo

    2007-08-15

    This is the fourth of a series of briefings which discuss the sustainable development issues raised by legal arrangements for the protection of foreign investment. The briefings are based on legal research by IIED and its partners. The goal is to provide accessible but accurate information for human rights, development and environmental organisations working on issues raised by foreign investment in low- and middle-income countries. Briefing 4 sets out some of the ways in which foreign investment contracts can impact on sustainable development.

  9. SUCCESSFUL REGISTRATION OF DOMESTIC BIOANALOGUE OF BEVACIZUMAB – NEW OPPORTUNITIES FOR EFFECTIVE TREA TMENT OF PATIENTS WITH NON-SQUAMOUS CELL NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    S. V. Orlov

    2015-01-01

    Full Text Available Comparison of the efficacy and safety of drugs "Avegra®" and "Avastin®" used in combination with paclitaxel and carboplatin as first-line therapy in patients with locally inoperable or metastatic NSCLC. The study included 138 patients, male and female aged 18 to 75 years with newly diagnosed inoperable or widespread metastatic NSCLC (except squamous cell NSCLC, relevant eligibility criteria. After passing screening, patients were centrally randomized in one of the study groups in a 1:1 ratio. Treatment was carried out according to the following scheme: "Avegra®" or "Avastin®", 15 mg/kg intravenously over 90 minutes immediately after carboplatin on day 1 of each 3‑week cycle + paclitaxel 175 mg/m² intravenously over 3 hours on day 1 of each 3‑week cycle + carboplatin dose required to achieve AUC 6 mg/ml×min, intravenously over 15–30 minutes, immediately following paclitaxel, on the first day of each three-week cycle. The treatment lasted for six cycles of three weeks or until progression or until the development of intolerable toxic effects. Based on CT scan assessment performed by an independent specialist, the overall response rate (ORR, partial response rate + complete response rate defined as a primary endpoint was 42.59% (95% CI 30.33–55.83% in "Avegra®" arm and 39.29% (95% CI 27.58–52.27% in "Avastin®" arm, respectively. The difference in ORR between study drug and comparator was 3.30% with 95% CI –14.96–21.40% (р =0.874, the Pearson x² test with Yates correction. The lower limit of calculated 95% CI (-14.96% exceeds the specified non-inferiority margin and it is indicating the non-inferiority of "Avegra®" efficacy compared to "Avastin®". During the study period the incidence of adverse events, including severe adverse events (grade 3–4 according to CTCAE related with the investigational drugs, did not have statistically significant differences in both study arms.The drug "Avegra®" in direct comparison to

  10. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

  11. Citizens Science for Sustainability (SuScit) Project Briefing

    DEFF Research Database (Denmark)

    Eames, Malcolm; Mortensen, Jonas Egmose; Adebowale, Maria

    This project briefing gives a short overview of the Citizens Science for Sustainability (SuScit) Project.......This project briefing gives a short overview of the Citizens Science for Sustainability (SuScit) Project....

  12. Extra-Curricular Inequality. Research Brief. Edition 1

    Science.gov (United States)

    Sutton Trust, 2014

    2014-01-01

    This Research Briefing analyses Office for National Statistics data and finds children from the most advantaged households benefit from significantly more spending on extra-curricular activities and private tutoring than their poorer peers. The brief also includes the Trust's annual polling on private tuition and new polling on parents and…

  13. My brief history

    CERN Document Server

    Hawking, Stephen

    2013-01-01

    My Brief History recounts Stephen Hawking’s improbable journey, from his postwar London boyhood to his years of international acclaim and celebrity. Lavishly illustrated with rarely seen photographs, this concise, witty, and candid account introduces readers to a Hawking rarely glimpsed in previous books: the inquisitive schoolboy whose classmates nicknamed him Einstein; the jokester who once placed a bet with a colleague over the existence of a particular black hole; and the young husband and father struggling to gain a foothold in the world of physics and cosmology. Writing with characteristic humility and humor, Hawking opens up about the challenges that confronted him following his diagnosis of ALS at age twenty-one. Tracing his development as a thinker, he explains how the prospect of an early death urged him onward through numerous intellectual breakthroughs, and talks about the genesis of his masterpiece A Brief History of Time—one of the iconic books of the twentieth century.

  14. Pre-surgery briefings and safety climate in the operating theatre.

    Science.gov (United States)

    Allard, Jon; Bleakley, Alan; Hobbs, Adrian; Coombes, Lee

    2011-08-01

    In 2008, the WHO produced a surgical safety checklist against a background of a poor patient safety record in operating theatres. Formal team briefings are now standard practice in high-risk settings such as the aviation industry and improve safety, but are resisted in surgery. Research evidence is needed to persuade the surgical workforce to adopt safety procedures such as briefings. To investigate whether exposure to pre-surgery briefings is related to perception of safety climate. Three Safety Attitude Questionnaires, completed by operating theatre staff in 2003, 2004 and 2006, were used to evaluate the effects of an educational intervention introducing pre-surgery briefings. Individual practitioners who agree with the statement 'briefings are common in the operating theatre' also report a better 'safety climate' in operating theatres. The study reports a powerful link between briefing practices and attitudes towards safety. Findings build on previous work by reporting on the relationship between briefings and safety climate within a 4-year period. Briefings, however, remain difficult to establish in local contexts without appropriate team-based patient safety education. Success in establishing a safety culture, with associated practices, may depend on first establishing unidirectional, positive change in attitudes to create a safety climate.

  15. ISAF Overview Brief

    Science.gov (United States)

    2011-01-01

    Eager Afghans NEW PA STUDENTS NATO / ISAF UNCLASSIFIED NATO / ISAF UNCLASSIFIED ISAF Overview Brief, MHS Conference 2011 – Attrition, Leader deficit...doctors (male/fem), 2 nurses, 2 midwives. 100k-300k XRAY, surgery, OB, physiotherapy , pediatrician, pharmacist, dentist. 10k-15k An extension of the BHC

  16. iPad-based patient briefing for radiological examinations-a clinical trial.

    Science.gov (United States)

    Schlechtweg, Philipp M; Hammon, Matthias; Giese, David; Heberlein, Christian; Uder, Michael; Schwab, Siegfried A

    2014-08-01

    To analyze if an iPad-based patient briefing can serve as a digital alternative to conventional documentations prior to radiological examinations. One hundred one patients referred for routine MRI were randomized into two groups, who underwent iPad-based and classic written briefing in opposite order. For each briefing completion time, completeness and correctness were noted. Patient's knowledge about the content of either briefing modality was subsequently tested. The influence of patient-related factors on the performance of the electronic briefing (EB) was analyzed. Finally, the patient's subjective impression of the EB was assessed. The mean durations were 4.4 ± 2.2 min for EB and 1.7 ± 1.3 min for the classic briefing (p iPad briefings were returned entirely filled out, whereas 11 % of the classic forms were returned with missing data. No significant differences in memorization of the briefing's information were objectified. There was a positive correlation between the duration of EB and age (r = 0.53; p iPads transfers the information for the patients equally well compared to the classic written approach. Although iPad briefing took patients longer to perform, the majority would prefer it to written consent briefings in the future. Nevertheless, measures have to be undertaken to improve the overall acceptance and performance.

  17. Patient and practitioner characteristics predict brief alcohol intervention in primary care.

    Science.gov (United States)

    Kaner, E F; Heather, N; Brodie, J; Lock, C A; McAvoy, B R

    2001-10-01

    The effectiveness of an evidence-based health care intervention depends on it being delivered consistently to appropriate patients. Brief alcohol intervention is known to be effective at reducing excessive drinking and its concomitant health and social problems. However, a recent implementation trial reported partial delivery of brief alcohol intervention by general practitioners (GPs) which is likely to have reduced its impact. To investigate patient-practitioner characteristics influencing brief alcohol intervention in primary care. Cross-sectional analysis of 12,814 completed Alcohol Use Disorders Identification Test (AUDIT) screening questionnaires. Eighty-four GPs who had implemented a brief alcohol intervention programme in a previous trial based in the Northeast of England. GPs were requested to screen all adults (aged over 16 years) presenting to their surgery and follow a structured protocol to give a brief intervention (five minutes of advice plus an information booklet) to all 'risk' drinkers. Anonymized carbon copies of the screening questionnaire were collected from all practices after a three-month implementation period. Although AUDIT identified 4080 'risk' drinkers, only 2043 (50%) received brief intervention. Risk drinkers that were most likely to receive brief intervention were males (58%), unemployed (61%), and technically-trained patients (55%). Risk drinkers that were least likely to receive brief intervention were females (44%), students (38%), and university educated patients (46%). Logistic regression modelling showed that patients' risk status was the most influential predictor of brief intervention. Also, GPs' experience of relevant training and longer average practice consultations predicted brief intervention. However, personal characteristics relating to patients and GPs also predicted brief intervention in routine practice. Interpersonal factors relating to patients and practitioners contributed to the selective provision of brief

  18. A Brief History.

    Science.gov (United States)

    Yalouris, Nicolaos

    1996-01-01

    Provides a brief but concise overview of the historical development of the Olympic Games in ancient Greece. Originally conceived as a one day, single-race event, the Games grew to the point where they represented an apotheosis of Greek culture. Discusses the role played by conflict within the city-states. (MJP)

  19. Sustainable Markets Investment Briefings: the regulatory taking doctrine

    Energy Technology Data Exchange (ETDEWEB)

    Cotula, Lorenzo

    2007-08-15

    This is the third of a series of briefings which discuss the sustainable development issues raised by legal arrangements for the protection of foreign investment. The briefings are based on legal research by IIED and its partners. The goal is to provide accessible but accurate information for human rights, development and environmental organisations working on issues raised by foreign investment in low- and middle-income countries. Briefing 3 introduces one of the most controversial legal doctrines of investment law – 'regulatory taking' – and sets out its implications for sustainable development.

  20. 'n Brief van strooi?: Die Evangelie in Jakobus

    Directory of Open Access Journals (Sweden)

    P. P. A. Kotz�

    1985-08-01

    Full Text Available Jakobus is 'n juweel. Dit is so jammer dat Luther die brief 'n slegte naam gegee het deur dit "eyn rechte stroern Epistel..." te noem, omdat dit, volgens hom, geen evangeliese inslag het nie ("den sie doch keyn Euangelisch art an yhr hat. So is dit as't ware 'ge�tiketteer' en die naam het bly kleef. Die meeste ondersoeke van die brief begin met die vermelding van Luther se uitspraak en probeer vanaf hierdie punt om die vaandel vir die brief te swaai, hetsy op Protestantse hetsy op Rooms - Katolieke wyse.

  1. Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme (GBM) cells due to c-Myc silencing.

    Science.gov (United States)

    Rajagopalan, Vishal; Vaidyanathan, Muthukumar; Janardhanam, Vanisree Arambakkam; Bradner, James E

    2014-10-01

    Glioblastoma Multiforme (GBM) is an aggressive form of brain Tumor that has few cures. In this study, we analyze the anti-proliferative effects of a new molecule JQ1 against GBMs induced in Wistar Rats. JQ1 is essentially a Myc inhibitor. c-Myc is also known for altering the biochemistry of a tumor cell. Therefore, the study is intended to analyze certain other oncogenes associated with c-Myc and also the change in cellular biochemistry upon c-Myc inhibition. The quantitative analysis of gene expression gave a co-expressive pattern for all the three genes involved namely; c-Myc, Bcl-2, and Akt. The cellular biochemistry analysis by transmission electron microscopy revealed high glycogen and lipid aggregation in Myc inhibited cells and excessive autophagy. The study demonstrates the role of c-Myc as a central metabolic regulator and Bcl-2 and Akt assisting in extending c-Myc half-life as well as in regulation of autophagy, so as to regulate cell survival on the whole. The study also demonstrates that transient treatment by JQ1 leads to aggressive development of tumor and therefore, accelerating death, emphasizing the importance of dosage fixation, and duration for clinical use in future.

  2. Analytical modeling of pulse-pileup distortion using the true pulse shape; applications to Fermi-GBM

    International Nuclear Information System (INIS)

    Chaplin, Vandiver; Bhat, Narayana; Briggs, Michael S.; Connaughton, Valerie

    2013-01-01

    Pulse-pileup affects most photon counting systems and occurs when photon detections occur faster than the detector's shaping and recovery time. At high input rates, shaped pulses interfere and the source spectrum, as well as intensity information, get distorted. For instruments using bipolar pulse shaping there are two aspects to consider: ‘peak’ and ‘tail’ pileup effects, which raise and lower the measured energy, respectively. Peak effects have been extensively modeled in the past. Tail effects have garnered less attention due to increased complexity. We leverage previous work to derive an accurate, semi-analytical prediction for peak and tail pileup including high order effects. We use the pulse shape of the detectors of the Fermi Gamma-ray Burst Monitor. The measured spectrum is calculated by expressing exposure time with a state-space expansion of overlapping pileup states and is valid up to very high rates. The model correctly predicts deadtime and pileup losses, and energy-dependent losses due to tail subtraction (sub-threshold) effects. We discuss total losses in terms of the true rate of photon detections versus the recorded count rate. -- Highlights: • A derivation of pulse-pileup spectral and intensity distortion is presented. • Applies to bipolar shaping instruments in general, but is calculated for Fermi-GBM. • Exposure time is partitioned with pulse widths as states of a Poisson process. • Each state has an associated energy distribution function for peak and tail pileup. • The total spectrum is the union of pulse states and their associated spectra

  3. 76 FR 50715 - Briefing on Partner Vetting System Pilot Program

    Science.gov (United States)

    2011-08-16

    ... Development Briefing on Partner Vetting System Pilot Program AGENCY: U.S. Department of State and U.S. Agency... briefing on the Partner Vetting System (PVS) pilot program. The objective of the briefing is to provide information about the PVS pilot program. Members of the public may attend in person or join via teleconference...

  4. Conventional Oil and Gas Technologies. IEA ETSAP technology brief P01

    Energy Technology Data Exchange (ETDEWEB)

    Seljom, Pernille [IFE (Norway)], E-mail: pernille.seljom@ife.no

    2010-05-15

    This technology brief on conventional oil and gas technologies is part of a series produced by the IEA ETSAP agreement called the energy technology data source (E-Tech-DS). The E-Tech-DS series consists of a number of 5-10 page technology briefs similar to the IEA Energy Technology Essentials. Based on the data collected for the models that the Energy Technology Systems Analysis Programme (ETSAP) is known for, ETSAP also prepares technology briefs, called E-TechDS. The E-TechDS briefs are standardized presentations of basic information (process, status, performance, costs, potential, and barriers) for key energy technology clusters. Each brief includes an overview of the technology, charts and graphs, and a summary data table, and usually ending with some key references and further information. The E TechDS briefs are intended to offer essential, reliable and quantitative information to energy analysts, experts, policymakers, investors and media from both developed and developing countries. This specific brief focuses on the state of oil and gas exploration, development, and production/recovery technologies.

  5. Clustering of gamma-ray burst types in the Fermi GBM catalogue: indications of photosphere and synchrotron emissions during the prompt phase

    Science.gov (United States)

    Acuner, Zeynep; Ryde, Felix

    2018-04-01

    Many different physical processes have been suggested to explain the prompt gamma-ray emission in gamma-ray bursts (GRBs). Although there are examples of both bursts with photospheric and synchrotron emission origins, these distinct spectral appearances have not been generalized to large samples of GRBs. Here, we search for signatures of the different emission mechanisms in the full Fermi Gamma-ray Space Telescope/GBM (Gamma-ray Burst Monitor) catalogue. We use Gaussian Mixture Models to cluster bursts according to their parameters from the Band function (α, β, and Epk) as well as their fluence and T90. We find five distinct clusters. We further argue that these clusters can be divided into bursts of photospheric origin (2/3 of all bursts, divided into three clusters) and bursts of synchrotron origin (1/3 of all bursts, divided into two clusters). For instance, the cluster that contains predominantly short bursts is consistent of photospheric emission origin. We discuss several reasons that can determine which cluster a burst belongs to: jet dissipation pattern and/or the jet content, or viewing angle.

  6. Case Briefs in Legal English Classes

    Directory of Open Access Journals (Sweden)

    Bilová Stĕpánka

    2016-06-01

    Full Text Available A case brief can be described as a succinct summary of a case which specifies the facts, procedural history, legal issue(s, court decision and legal reasoning supporting the judgment, even though exact formats may vary. Case briefing is a demanding activity which is required from students during their law studies. The goal is to teach students to focus on the essential parts of the case and to obtain a thorough understanding of the case and the reasoning, which means the students need to employ their analytical and critical thinking skills.

  7. ETV Tech Brief: Rapid Fungi and Bacteria Detection Technologies

    Science.gov (United States)

    Technical brief that summarizes the results for Mycometer, Inc. Mycometer®-test and Bactiquant®-test, which are rapid detection technologies for fungi and bacteria. The brief summarizes the results of the verification report and statement.

  8. 46 CFR 502.221 - Briefs; requests for findings.

    Science.gov (United States)

    2010-10-01

    ... presiding officer shall fix the time and manner of filing briefs and any enlargement of time. The period of... subject index or table of contents with page references and a list of authorities cited. (f) All briefs... pages containing the table of contents, table of authorities, and certificate of service, unless the...

  9. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  10. Can the documented patient briefing be carried out with an iPad app?

    Science.gov (United States)

    Schlechtweg, Philipp Martin; Hammon, Matthias; Heberlein, Christian; Giese, David; Uder, Michael; Schwab, Siegfried Alexander

    2013-06-01

    To evaluate the feasibility of an iPad-based documented patient briefing for Magnetic Resonance Imaging (MRI) examinations. A standard briefing sheet and questionnaire for a MRI scan was converted from paper form into an iPad application. Twenty patients, who had been referred for an MRI scan, were briefed about the examination in paper form as well as via the iPad application before performing the MRI scan. Time each patient needed for the briefing and the number of questions that came up were documented. Patients' acceptance of the electronic briefing was assessed using a questionnaire. The mean processing time was 2.36 min (range 0.58 to 09.35 min., standard deviation ±2.05 min) for the paper-based briefing and 4.15 min (range 1.56 to 13.48 min, SD ± 2.36 min) for the app-based briefing. Concerning technical aspects, patients asked two questions during the app-based briefing; no questions arose during the paper-based briefing. Six patients preferred electronic briefing and four patients, the paper-based form. No patient preferred the electronic form with additional multimedial information. Eight participants did not mind which briefing version was used; two participants did not express their preference at all. Our experiences showed that electronic briefing using an iPad is feasible and has the potential to become a user-friendly alternative to the conventional paper-based approach. Owing to the broad range of the results, a follow-up study will seek to determine the influencing factors on processing time and other potential questions.

  11. Environmental actual situation in Guatemala. Executive brief

    International Nuclear Information System (INIS)

    2000-01-01

    In this brief prepared by the Consejo Permanente de Cambio y Variabilidad Climatica the climate in Guatemala is described including the current situation on variation of rainy season, air humidity, influence of the Nino current. This brief was prepared in order to plan a strategy to be adopted by all the institutions that are involved in environmental issues and in this way to deal with the climate change and the impact of the different energy sources in the environment

  12. What Is Macular Edema?

    Medline Plus

    Full Text Available ... remains. Macular edema is often a complication of diabetic retinopathy , and is the most common form of ... 2016 Study Compares Eylea, Lucentis and Avastin for Diabetic Macular Edema Jul 17, 2015 Top 5 Risk ...

  13. Evaluation of a Brief Homework Assignment Designed to Reduce Citation Problems

    Science.gov (United States)

    Schuetze, Pamela

    2004-01-01

    I evaluated a brief homework assignment designed to reduce citation problems in research-based term papers. Students in 2 developmental psychology classes received a brief presentation and handout defining plagiarism with tips on how to cite sources to avoid plagiarizing. In addition, students in 1 class completed 2 brief homework assignments in…

  14. The influence of client brief and change order in construction project

    Science.gov (United States)

    Mahat, N. A. A.; Adnan, H.

    2018-02-01

    Construction briefing is a statement of needs about intentions and projects objectives. Briefing process is the preliminary stage in the design process and successful briefing can achieve project delivery right on target time, cost and quality of project confidently. Although there are many efforts to approach client’s requirement and needs for a project, it is still not collected adequately to make proper solutions in design. Thus, these may lead the client to include change orders during the construction phase. This paper is concerned toward the influence of client’s briefing of a construction project that impact on the change order on the construction works. The research objective is to identify the influence of client’s brief on change orders, therefore, the aims of the research is to reduce change orders in project delivery. This research adopted both qualitative and quantitative data collection methods which are content analysis and semi structure interview. The findings highlight factors contributing to change orders and the essential attributes of clients during the briefing stage that may help minimise them.

  15. The Briefing Book Concept.

    Science.gov (United States)

    Minix, Dean A.

    1990-01-01

    Describes an open admissions program, a public university's nontraditional population, and their unique academic needs. Provides a political science briefing book assignment in which students research and write about one country. Claims the book is effective in helping students to organize and focus their thoughts and to improve their research and…

  16. Effects of perioperative briefing and debriefing on patient safety: a prospective intervention study.

    Science.gov (United States)

    Leong, Katharina Brigitte Margarethe Siew Lan; Hanskamp-Sebregts, Mirelle; van der Wal, Raymond A; Wolff, Andre P

    2017-12-14

    This study was carried out to improve patient safety in the operating theatre by the introduction of perioperative briefing and debriefing, which focused on an optimal collaboration between surgical team members. A prospective intervention study with one pretest and two post-test measurements: 1 month before and 4 months and 2.5 years after the implementation of perioperative briefing and debriefing, respectively. Operating theatres of a tertiary care hospital with 875 beds in the Netherlands. All members of five surgical teams participated in the perioperative briefing and debriefing. The implementation of perioperative briefing and debriefing from July 2012 to January 2014. The primary outcome was changes in the team climate, measured by the Team Climate Inventory. Secondary outcomes were the experiences of surgical teams with perioperative briefing and debriefing, measured with a structured questionnaire, and the duration of the briefings, measured by an independent observer. Two and a half years after the introduction of perioperative briefing and debriefing, the team climate increased statistically significant (p≤0.05). Members of the five surgical teams strongly agreed with the positive influence of perioperative briefing and debriefing on clear agreements and reminding one another of the agreements of the day. They perceived a higher efficiency of the surgical programme with more operations starting on time and less unexpectedly long operation time. The perioperative briefing took less than 4 min to conduct. Perioperative briefing and debriefing improved the team climate of surgical teams and the efficiency of their work within the operating theatre with acceptable duration per briefing. Surgical teams with alternating team compositions have the most benefit of briefing and debriefing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  17. The early history of ideas on brief interventions for alcohol.

    Science.gov (United States)

    McCambridge, Jim; Cunningham, John A

    2014-04-01

    This study explores the early development of brief interventions for alcohol using a history of ideas approach with a particular focus on intervention content. The source publications of the key primary studies published from approximately 1962 to 1992 were examined, followed by a brief review of the earliest reviews in this field. These studies were placed in the context of developments in alcohol research and in public health. After early pioneering work on brief interventions, further advances were not made until thinking about alcohol problems and their treatment, most notably on controlled drinking, along with wider changes in public health, created new conditions for progress. There was then a golden era of rapid advance in the late 1980s and early 1990s, when preventing the development of problem drinking became important for public health reasons, in addition to helping already problematic drinkers. Many research challenges identified at that time remain to be met. The content of brief interventions changed over the period of study, although not in ways well informed by research advances, and there were also obvious continuities, with a renewed emphasis on the facilitation of self-change being one important consequence of the development of internet applications. Ideas about brief interventions have changed in important ways. Brief interventions have been studied with different populations of drinkers, with aims embracing both individual and population-level perspectives, and without well-specified contents. The brief intervention field is an appropriate target for further historical investigations, which may help thinking about addressing alcohol and other problems. © 2013 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  18. Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007.

    Science.gov (United States)

    Dubrow, Robert; Darefsky, Amy S

    2011-07-29

    We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM) and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes. We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages 30-69 years. We compared 15,088 GBM cases with 9,252 non-GBM cases. We used Poisson regression to calculate adjusted rate ratios and 95% confidence intervals. The GBM incidence rate increased proportionally with the 4th power of age, whereas the non-GBM rate increased proportionally with the square root of age. For each subtype, compared to non-Hispanic Whites, the incidence rate among Blacks, Asians/Pacific Islanders, and American Indians/Alaskan Natives was substantially lower (one-fourth to one-half for GBM; about two-fifths for non-GBM). Secondary to this primary effect, race/ethnic group variation in incidence was significantly less for non-GBM than for GBM. For each subtype, the incidence rate was higher for males than for females, with the male/female rate ratio being significantly higher for GBM (1.6) than for non-GBM (1.4). We observed significant calendar period trends of increasing incidence for GBM and decreasing incidence for non-GBM. For the two subtypes combined, we observed a 3% decrease in incidence between 1992-1995 and 2004-2007. The substantial difference in age effect between GBM and non-GBM suggests a fundamental difference in the genesis of primary GBM (the driver of GBM incidence) versus non-GBM. However, the commonalities between GBM and non-GBM with respect to race/ethnic group and sex variation, more notable than the somewhat subtle, albeit statistically significant, differences, suggest that within the context of a fundamental difference, some aspects of the complex process of

  19. Bevacizumab improves survival for patients with advanced cervical cancer

    Science.gov (United States)

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  20. Briefing Products - Tools for Communicating Technical Issues to a Non-Technical Audience

    International Nuclear Information System (INIS)

    Clark, Harvey; Foster, Kevin T.

    2011-01-01

    Briefing Products are a new NARAC/IMAAC product line designed to communicate the consequences of a radiological, nuclear, chemical or biological agent incident to non-technical decision makers and key leaders. Each Briefing Product addresses a single decision or issue focused on potential actions that should be considered when responding to a hazard, while avoiding the use of technical or regulatory jargon. Briefing Products do not make protective action recommendations, although they do concretely assist decision-makers with development of their own protective actions by quoting or paraphrasing the published guidance relevant to the decision at hand. Briefing Products are produced in sets tailored to specific types of incident which together depict the key decisions and characteristics of the incident. Each Briefing Product in the set consists of three elements: (1) Primary Effects, (2) Key Points and (3) Presenter Notes. Both the Primary Effects and Key Points are ready for direct presentation, while the Presenter Notes are designed to provide background information to the presenter and are not for direct presentation to the audience. The Briefing Products themselves are alternative presentations of results from the customary standard NARAC/IMAAC technical products. Currently, Briefing Products are available for detonation of both RDDs (Radiological Dispersal Devices) and INDs (Improvised Nuclear Devices). A new set of products tailored to nuclear power plant (NPP) accidents is currently under development. This paper describes the scope, structure and content of the Briefing Product sets. Examples from the two sets of Briefing Products now available are presented.

  1. Deep Learning for Computer Vision: A Brief Review

    Science.gov (United States)

    Doulamis, Nikolaos; Doulamis, Anastasios; Protopapadakis, Eftychios

    2018-01-01

    Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein. PMID:29487619

  2. Deep Learning for Computer Vision: A Brief Review

    Directory of Open Access Journals (Sweden)

    Athanasios Voulodimos

    2018-01-01

    Full Text Available Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.

  3. Deep Learning for Computer Vision: A Brief Review.

    Science.gov (United States)

    Voulodimos, Athanasios; Doulamis, Nikolaos; Doulamis, Anastasios; Protopapadakis, Eftychios

    2018-01-01

    Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.

  4. Alaska State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Alaska State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste generators in Alaska. The profile is the result of a survey of NRC licensees in Alaska. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Alaska

  5. 22 CFR 401.25 - Government brief regarding navigable waters.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Government brief regarding navigable waters. 401... PROCEDURE Applications § 401.25 Government brief regarding navigable waters. When in the opinion of the Commission it is desirable that a decision should be rendered which affects navigable waters in a manner or...

  6. Recent developments: Industry briefs

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This is the February 1992 'Industry Briefs' portion of the 'Recent Developments' section. Issues mentioned are: (1) closure of San Onofre Unit 1, (2) start-up of Penly Unit 2, (3) signing of a safeguards agreement with North Korea, (4) Canadian nuclear activities in Romania, and (5) the merger of two Japanese fuel cycle companies

  7. When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

    Science.gov (United States)

    Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

  8. Aikido: a model for brief strategic therapy.

    Science.gov (United States)

    Saposnek, D T

    1980-09-01

    Building on Watzlawick's observations of certain similarities between judo and brief strategic therapy, this paper develops theoretic and pragmatic parallels between brief strategic therapy and a sophisticated martial art system, Aikido. After presenting the contextual similarities of the two conceptual systems as parallel "challenges" to the therapist and Aikidoist to effect change, the similarities in basic principles of practice are presented. The similarities in the philosophical and attitudinal positions of these conceptual systems are then delineated, followed by a case example that integrates the various concepts in the paper.

  9. Organizational Structures to Support Oakland Community Schools. Knowledge Brief

    Science.gov (United States)

    John W. Gardner Center for Youth and Their Communities, 2015

    2015-01-01

    This brief is part of a series that shares findings from a research collaboration between the John W. Gardner Center for Youth and Their Communities at Stanford University and Oakland Unified School District (OUSD) focused on understanding implementation of the community school model in the district. This brief highlights findings related to…

  10. Three brief assessments of math achievement.

    Science.gov (United States)

    Steiner, Eric T; Ashcraft, Mark H

    2012-12-01

    Because of wide disparities in college students' math knowledge-that is, their math achievement-studies of cognitive processing in math tasks also need to assess their individual level of math achievement. For many research settings, however, using existing math achievement tests is either too costly or too time consuming. To solve this dilemma, we present three brief tests of math achievement here, two drawn from the Wide Range Achievement Test and one composed of noncopyrighted items. All three correlated substantially with the full achievement test and with math anxiety, our original focus, and all show acceptable to excellent reliability. When lengthy testing is not feasible, one of these brief tests can be substituted.

  11. Comparison of Brief Summary Formats Through a Health Literacy Lens.

    Science.gov (United States)

    Sharp, Michele L; Hall, Lori; Eleftherion, Anthony; Simpson, Katherine; Neuhauser, Linda

    2018-01-01

    Print pharmaceutical advertisements in the United States require inclusion of a brief summary of side effects, warnings, precautions, and contraindications from the labeling. The full package insert, which sponsors have traditionally used to fulfill the brief summary requirement, does not adhere to health literacy best practices, limiting its value to consumers. This study compared the understandability and usability of brief summaries in 3 formats designed to be more consumer friendly. Three brief summary formats were tested: (1) 2-column "Question and Answer"; (2) "Prescription Drug Facts Box," similar to current US over-the-counter drug facts labeling; and (3) "Health Literacy," based on clear communication principles. Researchers evaluated the formats using the Suitability Assessment of Materials (SAM) tool and conducted structured, scripted, one-on-one interviews (usability tests) with participants with estimated low to average education levels. This research was replicated across 2 therapeutic areas (type 2 diabetes and plaque psoriasis). SAM scores showed that the Health Literacy format outperformed the Question and Answer format and the Prescription Drug Facts Box format in both therapeutic areas, with both Health Literacy brief summaries rated on the SAM as "superior." Qualitative usability tests supported the SAM findings, with the Health Literacy format preferred consistently over the Question and Answer format, and more often than not over the Prescription Drug Facts Box format. Sponsors can employ a user-tested Health Literacy format to improve the understandability and usability of brief summaries with patients.

  12. Illinois State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1980-11-01

    The Illinois State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Illinois. The profile is the result of a survey of NRC licensees in Illinois. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Illinois

  13. Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007

    Directory of Open Access Journals (Sweden)

    Darefsky Amy S

    2011-07-01

    Full Text Available Abstract Background We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes. Methods We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages 30-69 years. We compared 15,088 GBM cases with 9,252 non-GBM cases. We used Poisson regression to calculate adjusted rate ratios and 95% confidence intervals. Results The GBM incidence rate increased proportionally with the 4th power of age, whereas the non-GBM rate increased proportionally with the square root of age. For each subtype, compared to non-Hispanic Whites, the incidence rate among Blacks, Asians/Pacific Islanders, and American Indians/Alaskan Natives was substantially lower (one-fourth to one-half for GBM; about two-fifths for non-GBM. Secondary to this primary effect, race/ethnic group variation in incidence was significantly less for non-GBM than for GBM. For each subtype, the incidence rate was higher for males than for females, with the male/female rate ratio being significantly higher for GBM (1.6 than for non-GBM (1.4. We observed significant calendar period trends of increasing incidence for GBM and decreasing incidence for non-GBM. For the two subtypes combined, we observed a 3% decrease in incidence between 1992-1995 and 2004-2007. Conclusions The substantial difference in age effect between GBM and non-GBM suggests a fundamental difference in the genesis of primary GBM (the driver of GBM incidence versus non-GBM. However, the commonalities between GBM and non-GBM with respect to race/ethnic group and sex variation, more notable than the somewhat subtle, albeit statistically significant, differences, suggest that within the context of a

  14. Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

    OpenAIRE

    Li, Rui; Li, Hailin; Yan, Wei; Yang, Pei; Bao, Zhaoshi; Zhang, Chuanbao; Jiang, Tao; You, Yongping

    2015-01-01

    Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and...

  15. Gbm.auto: A software tool to simplify spatial modelling and Marine Protected Area planning.

    Directory of Open Access Journals (Sweden)

    Simon Dedman

    Full Text Available Marine resource managers and scientists often advocate spatial approaches to manage data-poor species. Existing spatial prediction and management techniques are either insufficiently robust, struggle with sparse input data, or make suboptimal use of multiple explanatory variables. Boosted Regression Trees feature excellent performance and are well suited to modelling the distribution of data-limited species, but are extremely complicated and time-consuming to learn and use, hindering access for a wide potential user base and therefore limiting uptake and usage.We have built a software suite in R which integrates pre-existing functions with new tailor-made functions to automate the processing and predictive mapping of species abundance data: by automating and greatly simplifying Boosted Regression Tree spatial modelling, the gbm.auto R package suite makes this powerful statistical modelling technique more accessible to potential users in the ecological and modelling communities. The package and its documentation allow the user to generate maps of predicted abundance, visualise the representativeness of those abundance maps and to plot the relative influence of explanatory variables and their relationship to the response variables. Databases of the processed model objects and a report explaining all the steps taken within the model are also generated. The package includes a previously unavailable Decision Support Tool which combines estimated escapement biomass (the percentage of an exploited population which must be retained each year to conserve it with the predicted abundance maps to generate maps showing the location and size of habitat that should be protected to conserve the target stocks (candidate MPAs, based on stakeholder priorities, such as the minimisation of fishing effort displacement.By bridging the gap between advanced statistical methods for species distribution modelling and conservation science, management and policy, these

  16. The Potential Impact of Biofield Treatment on Human Brain Tumor Cells: A Time-Lapse Video Microscopy

    OpenAIRE

    Trivedi, Mahendra

    2015-01-01

    Study background: Glioblastoma (GBM) is the most common subtype of primary brain tumor in adults. The aim was to evaluate the impact of biofield treatment potential on human GBM and non-GBM brain cells using two time-lapse video microscopy technique. Methods: The human brain tumor, GBM cultured cells were divided into two groups viz. GBM control and GBM treatment. Similarly, human normal brain cultured cells (non-GBM) were taken and divided into two groups viz. non- GBM control and non-GB...

  17. Colorado State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The Colorado State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Colorado. The profile is the result of a survey of NRC licensees in Colorado. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Colorado

  18. Texas State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-08-01

    The Texas State Briefing Book is one of a series of state briefing books on low-level radioactivee waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Texas. The profile is the result of a survey of NRC licensees in Texas. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Texas.

  19. Tennessee State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-08-01

    The Tennessee State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Tennessee. The profile is the result of a survey of NRC licensees in Tennessee. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Tennessee.

  20. Florida State Briefing Book for low-level radioactive-waste management

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-06-01

    The Florida State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Florida. The profile is the result of a survey of NRC licensees in Florida. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Florida.

  1. California State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-12-01

    The California State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in California. The profile is the result of a survey of NRC licensees in California. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in California

  2. Massachusetts State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-01-01

    The Massachusetts State Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist State and Federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Massachusetts. The profile is the result of a survey of NRC licensees in Massachusetts. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Massachusetts

  3. Delaware State Briefing Book on low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Delaware State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Delaware. The profile is the result of a survey of NRC licensees in Delaware. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Delaware

  4. Massachusetts State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-03-12

    The Massachusetts State Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist State and Federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Massachusetts. The profile is the result of a survey of NRC licensees in Massachusetts. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Massachusetts.

  5. Utah State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-10-01

    The Utah State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Utah. The profile is the result of a survey of NRC licensees in Utah. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Utah.

  6. Indiana State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    Mitter, E.L.; Hume, R.D.; Briggs, H.R.; Feigenbaum, E.D.

    1981-01-01

    The Indiana State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Indiana. The profile is the result of a survey of NRC licensees in Indiana. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Indiana

  7. Kentucky State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Kentucky State Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist State and Federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Kentucky. The profile is the result of a survey of NRC licensees in Kentucky. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Kentucky

  8. Hawaii State briefing book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Hawaii State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Hawaii. The profile is the result of a survey of NRC licensees in Hawaii. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Hawaii

  9. Georgia State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Georgia State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Georgia. The profile is the result of a survey of NRC licensees in Georgia. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Georgia

  10. Oklahoma State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Oklahoma State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Oklahoma. The profile is the result of a survey of NRC licensees in Oklahoma. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Oklahoma

  11. Louisiana State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Louisiana State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Louisiana. The profile is a result of a survey of NRC licensees in Louisiana. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Louisiana

  12. Georgia State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-01-01

    The Georgia State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. This report contains a profile of low-level radioactive waste generators in Georgia. The profile is the result of a survey of NRC licensees in Georgia. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Georgia

  13. Wyoming State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-10-01

    The Wyoming State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Wyoming. The profile is the result of a survey of NRC licensees in Wyoming. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Wyoming.

  14. Kansas State Briefing Book on low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Kansas State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Kansas. The profile is the result of a survey of radioactive material licensees in Kansas. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Kansas

  15. Vermont State Briefing Book on low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Vermont State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Vermont. The profile is the result of a survey of Nuclear Regulatory Commission licensees in Vermont. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Vermont

  16. Tennessee State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Tennessee State Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist State and Federal Agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Tennessee. The profile is the result of a survey of NRC licensees in Tennessee. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Tennessee

  17. Tennessee State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Tennessee State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Tennessee. The profile is the result of a survey of NRC licensees in Tennessee. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Tennessee

  18. Wisconsin State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1980-11-01

    The Wisconsin State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Wisconsin. The profile is the result of a survey of NRC licensees in Wisconsin. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Wisconsin.

  19. Pennsylvania State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-04-01

    The Pennsylvania State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Pennsylvania. The profile is the result of a survey of NRC licensees in Pennsylvania. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Pennsylvania.

  20. Mississippi State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-08-01

    The Mississippi State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state an federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Mississippi. The profile is the result of a survey of NRC licensees in Mississippi. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Mississippi.

  1. Alabama State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Alabama State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. This report contains a profile of low-level radioactive waste generators in Alabama. The profile is the result of a survey of NRC licensees in Alabama. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Alabama

  2. Florida State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-06-01

    The Florida State Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist State and Federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Florida. The profile is the result of a survey of NRC licensees in Florida. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Florida

  3. Ohio State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-04-01

    The Ohio State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Ohio. The profile is the result of a survey of NRC licensees in Ohio. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Ohio

  4. Oklahoma State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Oklahoma State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Oklahoma. The profile is the result of a survey of NRC licensees in Oklahoma. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal cmmunications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Oklahoma

  5. Arizona State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The Arizona State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Arizona. The profile is the result of a survey of NRC licensees in Arizona. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Arizona

  6. Iowa State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Iowa State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. This report contains a profile of low-level radioactive waste generators in Iowa. The profile is the result of a survey of NRC licensees in Iowa. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Iowa

  7. Wyoming State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The Wyoming State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Wyoming. The profile is the result of a survey of NRC licensees in Wyoming. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Wyoming

  8. Washington State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1980-12-01

    The Washington State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Washington. The profile is the result of a survey of NRC licensees in Washington. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Washington.

  9. Arkansas State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Arkansas State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Arkansas. The profile is the result of a survey of NRC licensees in Arkansas. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Arkansas

  10. Vermont State Briefing Book on low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-01

    The Vermont State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Vermont. The profile is the result of a survey of Nuclear Regulatory Commission licensees in Vermont. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Vermont.

  11. Connecticut State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-06-01

    The Connecticut State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Connecticut. The profile is the result of a survey of Nuclear Regulatory Commission licensees in Connecticut. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Connecticut

  12. Wisconsin State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1980-11-01

    The Wisconsin State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Wisconsin. The profile is the result of a survey of NRC licensees in Wisconsin. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Wisconsin

  13. Idaho State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1980-12-01

    The Idaho State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Idaho. The profile is the result of a survey of NRC licensees in Idaho. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Idaho

  14. Virginia State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1980-11-01

    The Virginia State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Virginia. The profile is the result of a survey of NRC licensees in Virginia. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Virginia

  15. Oregon State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1980-12-01

    The Oregon State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Oregon. The profile is a result of a survey of NRC licensees in Oregon. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Oregon

  16. Washington State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1980-12-01

    The Washington State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Washington. The profile is the result of a survey of NRC licensees in Washington. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Washington

  17. Mississippi State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Mississippi State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state an federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Mississippi. The profile is the result of a survey of NRC licensees in Mississippi. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Mississippi

  18. Arkansas State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Arkansas State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. This report contains a profile of low-level radioactive waste generators in Arkansas. The profile is the result of a survey of NRC licensees in Arkansas. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Arkansas

  19. Florida State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-06-01

    The Florida State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Florida. The profile is the result of a survey of NRC licensees in Florida. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Florida

  20. Texas State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The Texas State Briefing Book is one of a series of state briefing books on low-level radioactivee waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Texas. The profile is the result of a survey of NRC licensees in Texas. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Texas

  1. Utah State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The Utah State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Utah. The profile is the result of a survey of NRC licensees in Utah. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Utah

  2. Maine State Briefing Book on low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-08-01

    The Maine State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and Federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Maine. The profile is the result of a survey of radioactive material licensees in Maine. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested partices including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant goverment agencies and activities, all of which may impact management practices in Maine.

  3. Ohio State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-04-01

    The Ohio State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Ohio. The profile is the result of a survey of NRC licensees in Ohio. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Ohio.

  4. Oregon State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1980-12-01

    The Oregon State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Oregon. The profile is a result of a survey of NRC licensees in Oregon. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Oregon.

  5. Pennsylvania State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-04-01

    The Pennsylvania State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Pennsylvania. The profile is the result of a survey of NRC licensees in Pennsylvania. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Pennsylvania

  6. A Brief Taxometrics Primer

    OpenAIRE

    Beauchaine, Theodore P.

    2007-01-01

    Taxometric procedures provide an empirical means of determining which psychiatric disorders are typologically distinct from normal behavioral functioning. Although most disorders reflect extremes along continuously distributed behavioral traits, identifying those that are discrete has important implications for accurate diagnosis, effective treatment, early identification of risk, and improved understanding of etiology. This article provides (a) brief descriptions of the conceptual bases of s...

  7. The efficacy of a brief group CBT program in treating patients diagnosed with bulimia nervosa: a brief report

    DEFF Research Database (Denmark)

    Jones, Allan; Clausen, Loa

    2013-01-01

    OBJECTIVE: The aim of the study was to evaluate the efficacy of a brief group cognitive behavior therapy (CBT) program in treating a large cohort of patients diagnosed with bulimia nervosa. METHOD: Treatment outcome defined as reductions in bulimia related behavioral symptoms and bulimia related...... distress was examined in 205 consecutive new patients enrolled in an eight-session group CBT program. RESULTS: Significant reductions in eating disorder pathology were found on all measures of bulimia related behavioral symptoms, as well as on all measures of bulimia related distress. DISCUSSION......: There is strong evidence for the efficacy of brief group CBT in treating patients with bulimia nervosa....

  8. Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain.

    Science.gov (United States)

    Lee, Se Jeong; Kang, Won Young; Yoon, Yeup; Jin, Ju Youn; Song, Hye Jin; Her, Jung Hyun; Kang, Sang Mi; Hwang, Yu Kyeong; Kang, Kyeong Jin; Joo, Kyeung Min; Nam, Do-Hyun

    2015-12-24

    Glioblastoma multiforme (GBM) is characterized by extensive local invasion, which is in contrast with extremely rare systemic metastasis of GBM. Molecular mechanisms inhibiting systemic metastasis of GBM would be a novel therapeutic candidate for GBM in the brain. Patient-derived GBM cells were primarily cultured from surgical samples of GBM patients and were inoculated into the brains of immune deficient BALB/c-nude or NOD-SCID IL2Rgamma(null) (NSG) mice. Human NK cells were isolated from peripheral blood mononucleated cells and expanded in vitro. Patient-derived GBM cells in the brains of NSG mice unexpectedly induced spontaneous lung metastasis although no metastasis was detected in BALB/c-nude mice. Based on the difference of the innate immunity between two mouse strains, NK cell activities of orthotopic GBM xenograft models based on BALB/c-nude mice were inhibited. NK cell inactivation induced spontaneous lung metastasis of GBM cells, which indicated that NK cells inhibit the systemic metastasis. In vitro cytotoxic activities of human NK cells against GBM cells indicated that cytotoxic activity of NK cells against GBM cells prevents systemic metastasis of GBM and that NK cells could be effective cell therapeutics against GBM. Accordingly, NK cells transplanted into orthotopic GBM xenograft models intravenously or intratumorally induced apoptosis of GBM cells in the brain and showed significant therapeutic effects. Our results suggest that innate NK immunity is responsible for rare systemic metastasis of GBM and that sufficient supplementation of NK cells could be a promising immunotherapeutic strategy for GBM in the brain.

  9. How Early Child Care Affects Later Development. Science Briefs

    Science.gov (United States)

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Are there Long-Term Effects of Early Child Care?" (J. Belsky, D. L. Vandell, M. Burchinal, K. A. Clarke-Stewart, K. McCartney, M. T. Owen, M. T., and The NICHD Early Child Care Research Network).…

  10. [Development of the Spanish brief-version of the University of California Performance Skills Assessment (Sp-UPSA-Brief) in patients with schizophrenia and bipolar disorder].

    Science.gov (United States)

    Garcia-Portilla, María Paz; Gomar, Jesús; Bobes-Bascaran, María Teresa; Menendez-Miranda, Isabel; Saiz, Pilar Alejandra; Muñiz, José; Arango, Celso; Patterson, Thomas; Harvey, Philip; Bobes, Julio; Goldberg, Terry

    2014-01-01

    In patients with severe mental disorders outcome measurement should include symptoms, cognition, functioning and quality of life at least. Shorter and efficient instruments have greater potential for pragmatic and valid clinical utility. Our aim was to develop the Spanish UPSA Brief scale (Sp-UPSA-Brief). Naturalistic, 6-month follow-up, multicentre study. 139 patients with schizophrenia, 57 with bipolar disorder and 31 controls were evaluated using the Sp-UPSA, CGI-S, GAF, and PSP. We conducted a multivariate linear regression model to identify candidate subscales for the Sp-UPSA-Brief. The stepwise regression model for patients with schizophrenia showed that communication and transportation Sp-UPSA subscales entered first and second at pbipolar disorder transportation and communication Sp-UPSA subscales entered first and second at pbipolar patients. Test-retest was 0.66 and 0.64 (pbipolar patients (p<0.0001).The Sp-UPSA-Brief discriminated between patients and controls. In schizophrenia patients it also discriminated among different levels of illness severity according to CGI-S scores. The Sp-UPSA-Brief is an alternate instrument to evaluate functional capacity that is valid and reliable. Having a shorter instrument makes it more feasible to assess functional capacity in patients with severe mental disorders, especially in everyday clinical practice. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

  11. Humans and Robots. Educational Brief.

    Science.gov (United States)

    National Aeronautics and Space Administration, Washington, DC.

    This brief discusses human movement and robotic human movement simulators. The activity for students in grades 5-12 provides a history of robotic movement and includes making an End Effector for the robotic arms used on the Space Shuttle and the International Space Station (ISS). (MVL)

  12. Minnesota State Briefing Book on low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Minnesota State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Minnesota. The profile is the result of a survey of Nuclear Regulatory Commission licensees in Minnesota conducted by the Minnesota Department of Health. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Minnesota

  13. A reusable magnetic graphene oxide-modified biosensor for vascular endothelial growth factor detection in cancer diagnosis.

    Science.gov (United States)

    Lin, Chih-Wen; Wei, Kuo-Chen; Liao, Shih-sheng; Huang, Chiung-Yin; Sun, Chia-Liang; Wu, Pei-Jung; Lu, Yu-Jen; Yang, Hung-Wei; Ma, Chen-Chi M

    2015-05-15

    Early cancer diagnosis is critical for the prevention of metastasis. However, simple and efficient methods are needed to improve the diagnosis and evaluation of cancer. Here, we propose a reusable biosensor based on a magnetic graphene oxide (MGO)-modified Au electrode to detect vascular endothelial growth factor (VEGF) in human plasma for cancer diagnosis. In this biosensor, Avastin is used as the specific biorecognition element, and MGO is used as the carrier for Avastin loading. The use of MGO enables rapid purification due to its magnetic properties, which prevents the loss of bioactivity. Moreover, the biosensor can be constructed quickly, without requiring a drying process, which is convenient for proceeding to detection. Our reusable biosensor provides the appropriate sensitivity for clinical diagnostics and has a wide range of linear detection, from 31.25-2000 pg mL(-1), compared to ELISA analysis. In addition, in experiments with 100% serum from clinical samples, readouts from the sensor and an ELISA for VEGF showed good correlation within the limits of the ELISA kit. The relative standard deviation (RSD) of the change in current (ΔC) for reproducibility of the Au biosensor was 2.36% (n=50), indicating that it can be reused with high reproducibility. Furthermore, the advantages of the Avastin-MGO-modified biosensor for VEGF detection are that it provides an efficient detection strategy that not only improves the detection ability but also reduces the cost and decreases the response time by 10-fold, indicating its potential as a diagnosis product. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  15. A Brief History of CME Science

    Science.gov (United States)

    Alexander, David; Richardson, Ian G.; Zurbuchen, Thomas H.

    2006-01-01

    We present here a brief summary of the rich heritage of observational and theoretical research leading to the development of our current understanding of the initiation, structure, and evolution of Coronal Mass Ejections.

  16. Screening and brief intervention for unhealthy drug use: little or no efficacy

    Directory of Open Access Journals (Sweden)

    Richard eSaitz

    2014-09-01

    Full Text Available Unhealthy drug use ranges from use that risks health harms through severe drug use disorders. This narrative review addresses whether screening and brief intervention, efficacious for risky alcohol use, has efficacy for reducing other drug use and consequences. Brief intervention among those seeking help shows some promise. Screening tools have been validated though most are neither brief nor simple enough for use in general health settings. Several randomized trials have tested the efficacy of brief intervention for unhealthy drug use identified by screening in general health settings (i.e. in people not seeking help for their drug use. Substantial evidence now suggests efficacy is limited or non-existent. Reasons likely include a range of actual and perceived severity (or lack of severity, concomitant unhealthy alcohol use and comorbid mental health conditions, and the wide range of types of unhealthy drug use (e.g. from marijuana, to prescription drugs, to heroin. Although brief intervention may have some efficacy for unhealthy drug users seeking help, the model of screening and brief intervention that has effects in primary care settings on risky alcohol use may not be efficacious for other drug use.

  17. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    Directory of Open Access Journals (Sweden)

    Bunce Catey

    2008-10-01

    Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

  18. Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Nitu Kumari

    2015-06-01

    Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin – an angiogenesis inhibitor against NF2 to inhibit protein–protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis.

  19. Clinical outcomes and cost-effectiveness of brief guided parent-delivered cognitive behavioural therapy and solution-focused brief therapy for treatment of childhood anxiety disorders: a randomised controlled trial.

    Science.gov (United States)

    Creswell, Cathy; Violato, Mara; Fairbanks, Hannah; White, Elizabeth; Parkinson, Monika; Abitabile, Gemma; Leidi, Alessandro; Cooper, Peter J

    2017-07-01

    Half of all lifetime anxiety disorders emerge before age 12 years; however, access to evidence-based psychological therapies for affected children is poor. We aimed to compare the clinical outcomes and cost-effectiveness of two brief psychological treatments for children with anxiety referred to routine child mental health settings. We hypothesised that brief guided parent-delivered cognitive behavioural therapy (CBT) would be associated with better clinical outcomes than solution-focused brief therapy and would be cost-effective. We did this randomised controlled trial at four National Health Service primary child and mental health services in Oxfordshire, UK. Children aged 5-12 years referred for anxiety difficulties were randomly allocated (1:1), via a secure online minimisation tool, to receive brief guided parent-delivered CBT or solution-focused brief therapy, with minimisation for age, sex, anxiety severity, and level of parental anxiety. The allocation sequence was not accessible to the researcher enrolling participants or to study assessors. Research staff who obtained outcome measurements were masked to group allocation and clinical staff who delivered the intervention did not measure outcomes. The primary outcome was recovery, on the basis of Clinical Global Impressions of Improvement (CGI-I). Parents recorded patient-level resource use. Quality-adjusted life-years (QALYs) for use in cost-utility analysis were derived from the Child Health Utility 9D. Assessments were done at baseline (before randomisation), after treatment (primary endpoint), and 6 months after treatment completion. We did analysis by intention to treat. This trial is registered with the ISCRTN registry, number ISRCTN07627865. Between March 23, 2012, and March 31, 2014, we randomly assigned 136 patients to receive brief guided parent-delivered CBT (n=68) or solution-focused brief therapy (n=68). At the primary endpoint assessment (June, 2012, to September, 2014), 40 (59%) children in

  20. The brief family relationship scale: a brief measure of the relationship dimension in family functioning.

    Science.gov (United States)

    Fok, Carlotta Ching Ting; Allen, James; Henry, David

    2014-02-01

    The Relationship dimension of the Family Environment Scale, which consists of the Cohesion, Expressiveness, and Conflict subscales, measures a person's perception of the quality of his or her family relationship functioning. This study investigates an adaptation of the Relationship dimension of the Family Environment Scale for Alaska Native youth. The authors tested the adapted measure, the Brief Family Relationship Scale, for psychometric properties and internal structure with 284 12- to 18-year-old predominately Yup'ik Eskimo Alaska Native adolescents from rural, remote communities. This non-Western cultural group is hypothesized to display higher levels of collectivism traditionally organized around an extended kinship family structure. Results demonstrate a subset of the adapted items function satisfactorily, a three-response alternative format provided meaningful information, and the subscale's underlying structure is best described through three distinct first-order factors, organized under one higher order factor. Convergent and discriminant validity of the Brief Family Relationship Scale was assessed through correlational analysis.

  1. Brief Behavioral Sleep Intervention for Adolescents: An Effectiveness Study.

    Science.gov (United States)

    Paavonen, E Juulia; Huurre, Taina; Tilli, Maija; Kiviruusu, Olli; Partonen, Timo

    2016-01-01

    Sleep disturbances are common among adolescents, but there are no brief interventions to treat them. The objective of this study was to evaluate the effectiveness of a brief semistructured, individually delivered sleep intervention to ameliorate adolescents' sleeping difficulties and lengthen sleep duration. All students aged 16-18 years in a high school were screened for sleeping difficulties and 36 students with the highest sleep problem scores were invited to the intervention. Postintervention improvements were observed on self-reported and actiwatch-registered sleep duration, self-reported sleep quality and sleep latency, perceived stress and anxiety (all p values sleep efficiency and sleep latency did not change (p > 0.05). A brief individual sleep intervention can be effective in lengthening sleep duration and improving subjective sleep quality and well-being among adolescents.

  2. The Computer-Assisted Brief Intervention for Tobacco (CABIT) Program: A Pilot Study

    OpenAIRE

    Boudreaux, Edwin D; Bedek, Kristyna L; Byrne, Nelson J; Baumann, Brigitte M; Lord, Sherrill A; Grissom, Grant

    2012-01-01

    Background Health care providers do not routinely carry out brief counseling for tobacco cessation despite the evidence for its effectiveness. For this intervention to be routinely used, it must be brief, be convenient, require little investment of resources, require little specialized training, and be perceived as efficacious by providers. Technological advances hold much potential for addressing the barriers preventing the integration of brief interventions for tobacco cessation into the he...

  3. Evaluating asthma websites using the Brief DISCERN instrument

    Directory of Open Access Journals (Sweden)

    Banasiak NC

    2017-06-01

    Full Text Available Nancy Cantey Banasiak,1 Mikki Meadows-Oliver2 1Pediatric Nurse Practitioner Specialty, Yale University School of Nursing, New Haven, CT, USA; 2University of Connecticut School of Nursing, Storrs, CT, USA Purpose: The primary purpose of this study was to examine the quality of sponsored and unsponsored asthma websites using the Brief DISCERN instrument and to evaluate whether the Health On the Net Code of Conduct (HONcode logo was present, thereby indicating that the site met the criteria. The Internet is an important source of health information for patients and their families. The primary purpose of this study was to examine the quality of sponsored and unsupported asthma websites. A secondary aim was to determine the readability and reading ease of the materials for each website along with the grade level. Methods: We queried seven Internet search engines using the keyword “asthma.” The websites were evaluated using the six-item Brief DISCERN instrument and by ascertaining whether the HONcode quality label was present. The websites were also evaluated for readability employing Flesch-Kincaid grade level and Flesch reading ease tools using Microsoft Office Word 2013 software. Results: A total of 22 unique websites were included in the study. Approximately 68% of the websites reviewed had a Brief DISCERN cutoff score of ≥16. The overall Brief DISCERN scores ranged from 6 to 30, and the mean score was 17.32 (SD =6.71. The Flesch-Kincaid grade level scores ranged from 2.9 to 15.4, and the average reading grade score was 9.49 (SD =2.7. The Flesch reading ease scores ranged from 17 to 82.7, with a mean reading ease score of 53.57 (SD =15.03. Sites with a HONcode quality label had significantly higher Brief DISCERN scores than those without one (t=2.3795; df=20; p=0.02. Conclusion: Brief DISCERN scores revealed that there is quality asthma information for children and their families available on the Internet. The grade level ranged between 2

  4. New Hampshire State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The New Hampshire State Briefing Book is one of a series of state briefing books based on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste generators in New Hampshire. The profile is the result of a survey of NRC licensees in New Hampshire. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in New Hampshire

  5. Bioethics: A brief review

    OpenAIRE

    Mandal, Jharna; Ponnambath, Dinoop Korol; Parija, Subhash Chandra

    2017-01-01

    Medical and life sciences research is a key driver in development, which leads to better quality of life. These pursuits can lead to discrimination, human rights violation, and injustice. The field of bioethics explores the ethical issues arising due to these advances in research and encompasses social, judicial, and environmental aspects affecting human beings. This brief review discusses the origin of bioethics, its principles, various international organizations, and their network involved...

  6. Recent developments: Industry briefs

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This article is the 'Industry Briefs' portion of Nuexco's July 1992 'Recent Developments' section. Specific items mentioned include: (1) the merger of Entergy and Gulf States Utilities, (2) restart of the Sequoyah Fuels facility in Oklahoma, (3) development of the 7th and 8th nuclear units in Taiwan, (4) purchase of interest in Rio Algom, Ltd, and (5) acquisition of the Italian firm AGIP by a Canadian company

  7. Brief Mindfulness Practices for Healthcare Providers - A Systematic Literature Review.

    Science.gov (United States)

    Gilmartin, Heather; Goyal, Anupama; Hamati, Mary C; Mann, Jason; Saint, Sanjay; Chopra, Vineet

    2017-10-01

    Mindfulness practice, where an individual maintains openness, patience, and acceptance while focusing attention on a situation in a nonjudgmental way, can improve symptoms of anxiety, burnout, and depression. The practice is relevant for health care providers; however, the time commitment is a barrier to practice. For this reason, brief mindfulness interventions (eg, ≤ 4 hours) are being introduced. We systematically reviewed the literature from inception to January 2017 about the effects of brief mindfulness interventions on provider well-being and behavior. Studies that tested a brief mindfulness intervention with hospital providers and measured change in well-being (eg, stress) or behavior (eg, tasks of attention or reduction of clinical or diagnostic errors) were selected for narrative synthesis. Fourteen studies met inclusion criteria; 7 were randomized controlled trials. Nine of 14 studies reported positive changes in levels of stress, anxiety, mindfulness, resiliency, and burnout symptoms. No studies found an effect on provider behavior. Brief mindfulness interventions may be effective in improving provider well-being; however, larger studies are needed to assess an impact on clinical care. Published by Elsevier Inc.

  8. Molecular Characteristics in MRI-classified Group 1 Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    William E Haskins

    2013-07-01

    Full Text Available Glioblastoma multiforme (GBM is a clinically and pathologically heterogeneous brain tumor. Previous study of MRI-classified GBM has revealed a spatial relationship between Group 1 GBM (GBM1 and the subventricular zone (SVZ. The SVZ is an adult neural stem cell niche and is also suspected to be the origin of a subtype of brain tumor. The intimate contact between GBM1 and the SVZ raises the possibility that tumor cells in GBM1 may be most related to SVZ cells. In support of this notion, we found that neural stem cell and neuroblast markers are highly expressed in GBM1. Additionally, we identified molecular characteristics in this type of GBM that include up-regulation of metabolic enzymes, ribosomal proteins, heat shock proteins, and c-Myc oncoprotein. As GBM1 often recurs at great distances from the initial lesion, the rewiring of metabolism and ribosomal biogenesis may facilitate cancer cells’ growth and survival during tumor migration. Taken together, combined our findings and MRI-based classification of GBM1 would offer better prediction and treatment for this multifocal GBM.

  9. New Jersey State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-04-01

    The New Jersey state Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in New Jersey. The profile is the result of a survey of NRC licensees in New Jersey. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in New Jersey.

  10. New Mexico State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The New Mexico State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in New Mexico. The profile is the result of a survey of NRC licensees in New Mexico. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in New Mexico

  11. New York State Briefing Book for low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-06-01

    The New York State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in New York. The profile is the result of a survey of NRC licensees in New York. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in New York

  12. South Carolina State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The South Carolina State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in South Carolina. The profile is the result of a survey of NRC licensees in South Carolina. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as definied by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in South Carolina

  13. North Dakota State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-10-01

    The North Dakota State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in North Dakota. The profile is the result of a survey of NRC licensees in North Dakota. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in North Dakota.

  14. West Virginia State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The West Virginia State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in West Virginia. The profile is the result of a survey of NRC licensees in West Virginia. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in West Virginia

  15. North Carolina State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-08-01

    The North Carolina State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in North Carolina. The profile is the result of a survey of NRC licensees in North Carolina. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in North Carolina

  16. Rhode Island State Briefing Book on low-level radioactive-waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-01

    The Rhode Island State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Rhode Island. The profile is the result of a survey of radioactive material licensees in Rhode Island. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Rhode Island.

  17. New Jersey State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-04-01

    The New Jersey state Briefing Book is one of a series of State briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in New Jersey. The profile is the result of a survey of NRC licensees in New Jersey. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in New Jersey

  18. North Dakota State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The North Dakota State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in North Dakota. The profile is the result of a survey of NRC licensees in North Dakota. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in North Dakota

  19. Rhode Island State Briefing Book on low-level radioactive-waste management

    International Nuclear Information System (INIS)

    1981-07-01

    The Rhode Island State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Rhode Island. The profile is the result of a survey of radioactive material licensees in Rhode Island. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may affect waste management practices in Rhode Island

  20. South Dakota State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The South Dakota State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in South Dakota. The profile is the result of a survey of NRC licensees in South Dakota. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in South Dakota

  1. South Carolina State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-08-01

    The South Carolina State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in South Carolina. The profile is the result of a survey of NRC licensees in South Carolina. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as definied by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in South Carolina.

  2. Puerto Rico State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-10-01

    The Puerto Rico State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Puerto Rico. The profile is the result of a survey of NRC licensees in Puerto Rico. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Puerto Rico

  3. North Carolina State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-08-01

    The North Carolina State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in North Carolina. The profile is the result of a survey of NRC licensees in North Carolina. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in North Carolina.

  4. Puerto Rico State Briefing Book for low-level radioactive waste management

    Energy Technology Data Exchange (ETDEWEB)

    1981-10-01

    The Puerto Rico State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Puerto Rico. The profile is the result of a survey of NRC licensees in Puerto Rico. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in Puerto Rico.

  5. My brief history. 2. ed.

    International Nuclear Information System (INIS)

    Hawking, Stephen

    2015-01-01

    For the first time, Stephen Hawking turns his gaze inward for a revealing look at his own life and intellectual evolution. My Brief History recounts Stephen Hawking's improbable journey, from his post-war London boyhood to his years of international acclaim and celebrity. Illustrated with rarely seen photographs, this concise, witty and candid account introduces readers to the inquisitive schoolboy whose classmates nicknamed him 'Einstein'; the jokester who once placed a bet with a colleague over the existence of a black hole; and the young husband and father striving to gain a foothold in the world of academia. Writing with humility and humour, Hawking opens up about the challenges that confronted him following his diagnosis of ALS aged twenty-one. Tracing his development as a thinker, he explains how the prospect of an early death urged him onward through numerous intellectual breakthroughs, and talks about the genesis of his masterpiece A Brief History of Time - one of the iconic books of the twentieth century.

  6. Competency-Based Business Degree. Issue Brief

    Science.gov (United States)

    Washington State Board for Community and Technical Colleges, 2014

    2014-01-01

    In January 2015, thirteen Washington community colleges launched an online, competency-based business transfer degree--the first in the state's community and technical college system. This issue brief provides answers to commonly asked questions about the new competency-based degree.

  7. Promoting Savings at Tax Time through a Video-Based Solution-Focused Brief Coaching Intervention

    Directory of Open Access Journals (Sweden)

    Lance Palmer

    2016-09-01

    Full Text Available Solution-focused brief coaching, based on solution-focused brief therapy, is a well-established practice model and is used widely to help individuals progress toward desired outcomes in a variety of settings. This papers presents the findings of a pilot study that examined the impact of a video-based solution-focused brief coaching intervention delivered in conjunction with income tax preparation services at a Volunteer Income Tax Assistance location (n = 212. Individuals receiving tax preparation assistance were randomly assigned to one of four treatment groups: 1 control group; 2 video-based solution-focused brief coaching; 3 discount card incentive; 4 both the video-based solution-focused brief coaching and the discount card incentive. Results of the study indicate that the video-based solution-focused brief coaching intervention increased both the frequency and amount of self-reported savings at tax time. Results also indicate that financial therapy based interventions may be scalable through the use of technology.

  8. Brief debrisoquin administration to assess central dopaminergic function in children.

    Science.gov (United States)

    Riddle, M A; Shaywitz, B A; Leckman, J F; Anderson, G M; Shaywitz, S E; Hardin, M T; Ort, S I; Cohen, D J

    1986-03-17

    Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.

  9. Brief Treatment for Borderline and Narcissistic Couples: Working the Reenactment Spiral.

    Science.gov (United States)

    Clark, Steven

    1997-01-01

    Develops a brief, psychoanalytically informed treatment model for borderline and narcissistic couples. Advantages and disadvantages as well as treatment principles of brief treatment for this population are explored. Phases of treatment are reviewed with an emphasis on process and interventions. Explores managing the spiraling escalation of affect…

  10. The Role of Protein Kinase CK2 in Glioblastoma Development

    OpenAIRE

    Ji, Haitao; Lu, Zhimin

    2013-01-01

    Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor in adults, and its response to current therapies is limited. Protein kinase CK2 is overexpressed in GBM and regulates GBM cell survival, proliferation, and migration and brain tumorigenesis. Targeting CK2 for GBM treatment may benefit GBM patients.

  11. The effect of briefing videos in medical simulation-based education : a randomised controlled trial

    NARCIS (Netherlands)

    van Tetering, A.A.C.; Truijens, S.E.M.; van der Hout - van der Jagt, M.B.; Wijsman, J.L.P; Oei, S.G.

    2014-01-01

    The aim of this study is to compare the effects of an affective briefing video with a textual briefing on cognitive appraisal (threat or challenge response). It is hypothesized that briefing videos will cause a threat response, which is associated with increase in cortisol and memory consolidation4.

  12. Author Details

    African Journals Online (AJOL)

    ... Retinal Vein Occlusion in Onitsha, Nigeria Abstract PDF · Vol 19, No 1 (2011) - Articles Survey of Cataract Surgical Techniques in Nigeria Abstract PDF · Vol 19, No 1 (2011) - Articles Initial Experience with Bevacizumab (AvastinTM) in the Treatment of Neovascular Age-related Macular Degeneration in Nigerian Patients

  13. Brief Adlerian psychodynamic psychotherapy: theoretical issues and process indicators.

    Science.gov (United States)

    Fassino, S; Amianto, F; Ferrero, A

    2008-06-01

    Brief psychotherapy is gaining interest worldwide, because of its good cost/effectiveness ratio and proved efficacy. The aim of the paper was to describe the brief Adlerian psychodynamic psychotherapy (B-APP): a brief, psychodynamically oriented psychotherapy referring to the individual psychology (IP). The B-APP theory refers to the following paradigms: 1) the individual represents a psychosomatic unity integrated in the social context; 2) the individual needs to build and regulate the image of the self; 3) bond patterns regulate human relationships and represent the symbolic ''fil rouge'' connecting the elements of the life-style. Its objectives are: 1) an at least partial resolution of the focus problem; 2) a decrease or a non-increase of symptoms; 3) a global increase of quality of life. The results depend on intrapsychic and relational changes. Indications are more relative than absolute. The possibility of identifying a meaningful focus is fundamental. The treatment scheme includes 15 sessions subdivided into 5 phases. B-APP offers a technical approach to brief psychotherapy which is suitable in many fields of psychiatry and liaison medicine such as preventive interventions in at-risk subjects, somatopsychic disorders and liaison psychiatry, personality and eating disorders, and treatment of emotionally disturbed children. It was applied as psychotherapeutic approach in some clinical outcome studies about eating disorders and severe personality disorders displaying a good efficacy.

  14. Linking Brief Functional Analysis to Intervention Design in General Education Settings

    Science.gov (United States)

    Ishuin, Tifanie

    2009-01-01

    This study focused on the utility and applicability of brief functional analysis in general education settings. The purpose of the study was to first identify the environmental variables maintaining noncompliance through a brief functional analysis, and then to design and implement a functionally equivalent intervention. The participant exhibited…

  15. Gender Brief on ADRA (Adventist Development and Relief Organisation) in Rwanda

    DEFF Research Database (Denmark)

    Madsen, Diana Højlund

    The Gender Brief is based on focus groups interviews in Rwanda on the gender perspectives of ADRA-Rwanda and gives recommendations for the organisation.......The Gender Brief is based on focus groups interviews in Rwanda on the gender perspectives of ADRA-Rwanda and gives recommendations for the organisation....

  16. {sup 18}F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro [Graduate School of Medicine, Hokkaido University, Department of Neurosurgery, Sapporo (Japan); Hattori, Naoya [Graduate School of Medicine, Hokkaido University, Department of Molecular Imaging, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Department of Radiology, Sapporo (Japan); Tanaka, Shinya [Graduate School of Medicine, Hokkaido University, Department of Cancer Pathology, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2012-05-15

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that {sup 18}F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and {sup 18}F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p {<=} 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 {+-} 0.60, range 1.71-3.81) than in non-GBM patients (1.22 {+-} 0.06, range 1.09-1.29, p {<=} 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also

  17. 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    International Nuclear Information System (INIS)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro; Hattori, Naoya; Magota, Keiichi; Tanaka, Shinya; Kuge, Yuji

    2012-01-01

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18 F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and 18 F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71-3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09-1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM

  18. Issue briefs on low-level radioactive wastes

    International Nuclear Information System (INIS)

    1981-01-01

    This report contains 4 Issue Briefs on low-level radioactive wastes. They are entitled: Handling, Packaging, and Transportation, Economics of LLW Management, Public Participation and Siting, and Low Level Waste Management

  19. Quality Physical Education. NASPE Resource Brief

    Science.gov (United States)

    National Association for Sport and Physical Education, 2013

    2013-01-01

    A quality physical education program provides learning opportunities, appropriate instruction, meaningful and challenging content, and student and program assessment. In addition, a quality physical education improves mental alertness, academic performance, and readiness and enthusiasm for learning in the nation's youth. This brief provides a list…

  20. Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted?

    OpenAIRE

    Liu, Patricia; Waheed, Sana; Boujelbane, Lamya; Maursetter, Laura J.

    2016-01-01

    Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occu...

  1. Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

    OpenAIRE

    Steblay, R. W.; Rudofsky, U. H.

    1983-01-01

    The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared b...

  2. A brief assessment of physical functioning for prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Jin-Shei Lai

    2010-06-01

    Full Text Available Jin-Shei Lai1, Rita Bode2, Hwee-Lin Wee3, David Eton4, David Cella11Department of Medical Social Sciences, 2Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, IL USA; 3Department of Pharmacy, National University of Singapore, Singapore; 4Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USAAbstract: We aimed to validate a more rapid, yet reliable means of assessing physical function (PF for patients with prostate cancer. The sample included 128 prostate cancer patients recruited from urology and general oncology clinics at two Chicago-area hospitals. The main outcome measures were: A 36-item PF item bank that included a 5-item short form (BriefPF and the 10-item PF subscale (PF-10 from the Medical Outcomes Study SF-36. Validity, information function, and relative precision (calculated using Rasch analysis and raw scores of the BriefPF were compared to the PF-10 and the full PF item bank. We found that the BriefPF and PF-10 were strongly correlated (r = 0.85 with the PF bank, and all three scales differentiated patients according to performance status (FPF bank(2,124 = 32.51 P < 0.001, FPF-10(2,121 = 27.35 P < 0.001, FBriefPF (2,123 = 38.40 P < 0.001. BriefPF has excellent precision relative to the PF-10 in measuring patients with different performance status levels. The Rasch-based information function indicated that the BriefPF was more informative than PF-10 in measuring moderate to higher functioning patients. Hence, the BriefPF offers a parsimonious and precise measure of PF for use among men with prostate cancer, and may aid in the timely inclusion of patient-reported outcomes in treatment decision-making.Keywords: quality-of-life, item bank, short-form, Medical Outcomes Study

  3. Herpes Simplex Virus (HSV-1 Encephalitis Mimicking Glioblastoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Burke A. Cunha

    2014-12-01

    Full Text Available Glioblastoma multiforme (GBM often presents as a brain mass with encephalitis. In a patient with GBM, subsequent presentation with new onset encephalitis may be due to another GBM or Herpes simplex virus 1 (HSV-1 encephalitis. We present a case of HSV-1 encephalitis mimicking GBM in a patient with previous GBM.

  4. Economic School Integration: An Update. The Century Foundation Issue Brief Series.

    Science.gov (United States)

    Kahlenberg, Richard D.

    In 2000, an Idea Brief asserted that the best way to improve education would be to give every schoolchild the opportunity to attend a middle class public school (economic school integration). This brief reviews recent research and policy developments regarding economic school integration, noting that school segregation based on socioeconomic…

  5. Efficacy of a brief image-based multiple-behavior intervention for college students.

    Science.gov (United States)

    Werch, Chudley E; Moore, Michele J; Bian, Hui; DiClemente, Carlo C; Ames, Steven C; Weiler, Robert M; Thombs, Dennis; Pokorny, Steven B; Huang, I-Chan

    2008-10-01

    Epidemiologic data indicate most adolescents and adults experience multiple, simultaneous risk behaviors. The purpose of this study is to examine the efficacy of a brief image-based multiple-behavior intervention (MBI) for college students. A total of 303 college students were randomly assigned to: (1) a brief MBI or (2) a standard care control, with a 3-month postintervention follow-up. Omnibus treatment by time multivariate analysis of variance interactions were significant for three of six behavior groupings, with improvements for college students receiving the brief MBI on alcohol consumption behaviors, F(6, 261) = 2.73, p = 0.01, marijuana-use behaviors, F(4, 278) = 3.18, p = 0.01, and health-related quality of life, F(5, 277) = 2.80, p = 0.02, but not cigarette use, exercise, and nutrition behaviors. Participants receiving the brief MBI also got more sleep, F(1, 281) = 9.49, p = 0.00, than those in the standard care control. A brief image-based multiple-behavior intervention may be useful in influencing a number of critical health habits and health-related quality-of-life indicators of college students.

  6. Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes.

    Science.gov (United States)

    Chen, Yang; Gao, Zhen; Wang, Bingcheng; Xu, Rong

    2016-08-22

    Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.

  7. A brief history of the universe

    International Nuclear Information System (INIS)

    Sinha, K.K.

    1992-10-01

    The failure of the Big Bang Theory to explain the experimental (cosmological) data is well known. Attempts have been made to give a new interpretation of the above theory to explain the existing cosmological problems and a brief history of the universe. (author). 2 refs, 1 fig

  8. Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

    International Nuclear Information System (INIS)

    Jan, S.; Khan, M.N.; Karim, S.; Khan, M.T.; Hussain, Z.; Khan, S.; Nazim, M.

    2010-01-01

    Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

  9. Executive-style briefings on selected repository design issues

    International Nuclear Information System (INIS)

    1978-01-01

    This document is a collection of executive-style briefings on selected repository design issues. Most of the briefings discuss differences between the US repository design bases presented in US Working Draft on Repository Physical Descriptions in a Salt Formation, prepared in support of INFCE discussions of May 1978 and the FRG-Netherlands design bases, presented in Design Study of a Radioactive Waste Repository to be Mined in a Medium-Size Salt Dome by Hamstra and Velzeboer, Netherlands Energy Research Foundation, January 1978. Advantages and disadvantages of the two sets of design bases are discussed, and the impacts of adopting either of these bases on the other's programs and positions are identified

  10. Renewable energy. From marginal to mainstream. Policy Brief

    Energy Technology Data Exchange (ETDEWEB)

    Veum, K.C.; Uslu, A.; De Coninck, H.C. [ECN Policy Studies, Petten (Netherlands)

    2013-04-15

    This policy brief aims to instigate a debate on the broader enabling conditions required to move renewable energy from marginal shares in the European energy system to a mainstream role. It does so by posing seven key questions related to public movement, the political-industrial complex, resources and sustainability, grids and markets, finance, legal procedures and overall policy. These questions require short- to medium-term attention to keep a long-term renewable energy system within the realm of possibilities. This policy brief also provides ECN's initial reflections on how these key questions could be addressed, and indicates which relevant expertise it can bring to the table.

  11. STS-114: Discovery Crew Post Landing Press Briefing

    Science.gov (United States)

    2005-01-01

    The crew of the STS-114 Discovery is shown during a post landing press briefing. Commander Collins introduces the crew members who consist of Pilot Jim Kelley, Mission Specialist Soichi Noguchi from JAXA, Steve Robinson, Mission Specialist and Charlie Camarda, Mission Specialist. Steve Robinson answers a question from the news media about the repair that he performed in orbit, and his feelings about being back in his hometown of California. Commander Collins talks about the most significant accomplishment of the mission. The briefing ends as each crewmember reflects on the Space Shuttle Columbia tragedy and expresses their personal thoughts and feelings as they re-entered the Earth's atmosphere.

  12. Cross-cultural adaptation and measurement properties of the Brief Illness Perception Questionnaire-Dutch Language Version

    NARCIS (Netherlands)

    Carin Schröder; Francois Maissan; Edwin de Raaij; Jan Pool; Dr. H.M. Wittink

    2012-01-01

    OBJECTIVE: Ever since Engel's Biopsychosocial Model (1977) emotions, thoughts, beliefs and behaviors are accepted as important factors of health. The Brief Illness Perception Questionnaire (Brief IPQ) assesses these beliefs. Aim of this study was to cross-culturally adapt the Brief IPQ into the

  13. Biomimetic strategies for the glioblastoma microenvironment

    Science.gov (United States)

    Cha, Junghwa; Kim, Pilnam

    2017-12-01

    Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity, and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

  14. Brief narrative exposure therapy for posttraumatic stress in Iraqi refugees: a preliminary randomized clinical trial.

    Science.gov (United States)

    Hijazi, Alaa M; Lumley, Mark A; Ziadni, Maisa S; Haddad, Luay; Rapport, Lisa J; Arnetz, Bengt B

    2014-06-01

    Many Iraqi refugees suffer from posttraumatic stress. Efficient, culturally sensitive interventions are needed, and so we adapted narrative exposure therapy into a brief version (brief NET) and tested its effects in a sample of traumatized Iraqi refugees. Iraqi refugees in the United States reporting elevated posttraumatic stress (N = 63) were randomized to brief NET or waitlist control conditions in a 2:1 ratio; brief NET was 3 sessions, conducted individually, in Arabic. Positive indicators (posttraumatic growth and well-being) and symptoms (posttraumatic stress, depressive, and somatic) were assessed at baseline and 2- and 4-month follow-up. Treatment participation (95.1% completion) and study retention (98.4% provided follow-up data) were very high. Significant condition by time interactions showed that those receiving brief NET had greater posttraumatic growth (d = 0.83) and well-being (d = 0.54) through 4 months than controls. Brief NET reduced symptoms of posttraumatic stress (d = -0.48) and depression (d = -0.46) more, but only at 2 months; symptoms of controls also decreased from 2 to 4 months, eliminating condition differences at 4 months. Three sessions of brief NET increased growth and well-being and led to symptom reduction in highly traumatized Iraqi refugees. This preliminary study suggests that brief NET is both acceptable and potentially efficacious in traumatized Iraqi refugees. Copyright © 2014 International Society for Traumatic Stress Studies.

  15. Michigan State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1980-11-01

    The Michigan State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in Michigan. The profile is the result of a survey of NRC licensees in Michigan. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the discussion of relevant government agencies and activities, all of which may impact waste management practices in Michigan

  16. A Step Toward High Reliability: Implementation of a Daily Safety Brief in a Children's Hospital.

    Science.gov (United States)

    Saysana, Michele; McCaskey, Marjorie; Cox, Elaine; Thompson, Rachel; Tuttle, Lora K; Haut, Paul R

    2017-09-01

    Health care is a high-risk industry. To improve communication about daily events and begin the journey toward a high reliability organization, the Riley Hospital for Children at Indiana University Health implemented a daily safety brief. Various departments in our children's hospital were asked to participate in a daily safety brief, reporting daily events and unexpected outcomes within their scope of responsibility. Participants were surveyed before and after implementation of the safety brief about communication and awareness of events in the hospital. The length of the brief and percentage of departments reporting unexpected outcomes were measured. The analysis of the presurvey and the postsurvey showed a statistically significant improvement in the questions related to the awareness of daily events as well as communication and relationships between departments. The monthly mean length of time for the brief was 15 minutes or less. Unexpected outcomes were reported by 50% of the departments for 8 months. A daily safety brief can be successfully implemented in a children's hospital. Communication between departments and awareness of daily events were improved. Implementation of a daily safety brief is a step toward becoming a high reliability organization.

  17. The Brief Early Childhood Screening Assessment: Preliminary Validity in Pediatric Primary Care.

    Science.gov (United States)

    Fallucco, Elise M; Wysocki, Tim; James, Lauren; Kozikowski, Chelsea; Williams, Andre; Gleason, Mary M

    Brief, well-validated instruments are needed to facilitate screening for early childhood behavioral and emotional problems (BEPs). The objectives of this study were to empirically reduce the length of the Early Childhood Screening Assessment (ECSA) and to assess the validity and reliability of this shorter tool. Using caregiver ECSA responses for 2467 children aged 36 to 60 months seen in primary care, individual ECSA items were ranked on a scale ranging from "absolutely retain" to "absolutely delete." Items were deleted sequentially beginning with "absolutely delete" and going up the item prioritization list, resulting in 35 shorter versions of the ECSA. A separate primary care sample (n = 69) of mothers of children aged 18 to 60 months was used to determine the sensitivity and specificity of each shorter ECSA version using psychiatric diagnosis on the Diagnostic Infant and Preschool Assessment as the gold standard. The version with the optimal balance of sensitivity, specificity, and length was selected as the Brief ECSA. Associations between Brief ECSA scores and other pertinent measures were evaluated to estimate reliability and validity. A 22-item measure reflected the best combination of brevity, sensitivity and specificity. A cutoff score of 9 or higher on the 22-item Brief ECSA demonstrated acceptable sensitivity (89%) and specificity (85%) for predicting a psychiatric diagnosis. Brief ECSA scores correlated significantly and in expected directions with scores on pertinent measures and with demographic variables. The results indicate that the Brief ECSA has sound psychometric properties for identifying young children with BEPs in primary care.

  18. Drought Resilience and Water Conservation Technical Brief

    Science.gov (United States)

    In many areas of the US, the frequency, intensity, and duration of drought events are increasing, this brief highlights EPA drought and conservation activities across the nation and includes links to additional materials and reference documents.

  19. BIRC3 is a biomarker of mesenchymal habitat of glioblastoma, and a mediator of survival adaptation in hypoxia-driven glioblastoma habitats.

    Science.gov (United States)

    Wang, Dapeng; Berglund, Anders E; Kenchappa, Rajappa S; MacAulay, Robert J; Mulé, James J; Etame, Arnold B

    2017-08-24

    Tumor hypoxia is an established facilitator of survival adaptation and mesenchymal transformation in glioblastoma (GBM). The underlying mechanisms that direct hypoxia-mediated survival in GBM habitats are unclear. We previously identified BIRC3 as a mediator of therapeutic resistance in GBM to standard temozolomide (TMZ) chemotherapy and radiotherapy (RT). Here we report that BIRC3 is a biomarker of the hypoxia-mediated adaptive mesenchymal phenotype of GBM. Specifically, in the TCGA dataset elevated BIRC3 gene expression was identified as a superior and selective biomarker of mesenchymal GBM versus neural, proneural and classical subtypes. Further, BIRC3 protein was highly expressed in the tumor cell niches compared to the perivascular niche across multiple regions in GBM patient tissue microarrays. Tumor hypoxia was found to mechanistically induce BIRC3 expression through HIF1-alpha signaling in GBM cells. Moreover, in human GBM xenografts robust BIRC3 expression was noted within hypoxic regions of the tumor. Importantly, selective inhibition of BIRC3 reversed therapeutic resistance of GBM cells to RT in hypoxic microenvironments through enhanced activation of caspases. Collectively, we have uncovered a novel role for BIRC3 as a targetable biomarker and mediator of hypoxia-driven habitats in GBM.

  20. Implementation of brief alcohol interventions by nurses in primary care: do non-clinical factors influence practice?

    Science.gov (United States)

    Lock, Catherine A; Kaner, Eileen F S

    2004-06-01

    In the UK, GPs and practice nurses selectively provide brief alcohol interventions to risk drinkers. GPs' provision of a brief alcohol intervention can be predicted by patient characteristics, practitioner characteristics and structural factors such as the features of the practice and how it is organized. However, much less is known about possible modifiers of nurse practice. Our aim was to investigate if patient characteristics, nurse characteristics and practice factors influence provision of a brief alcohol intervention by practice nurses in primary health care. One hundred and twenty-eight practice nurses who had implemented a brief alcohol intervention programme in a previous trial based in the North of England were requested to screen adults presenting to their surgery and follow a structured protocol to give a brief intervention (5 min of advice plus an information booklet) to all 'risk' drinkers. Anonymized carbon copies of 5541 completed Alcohol Use Disorders Identification Test (AUDIT) screening questionnaires were collected after a 3-month implementation period and analysed by logistic regression analysis. Although AUDIT identified 1500 'risk' drinkers, only 926 (62%) received a brief intervention. Logistic regression modelling showed that patients' risk status as measured by AUDIT score was the most influential predictor of a brief intervention by practice nurses. However, risk drinkers who were most likely to receive a brief intervention were male. Patients' age or social class did not independently predict a brief intervention. The multilevel model was unable to identify any independent nurse characteristics that could predict a brief intervention, but indicated significant variation between nurses in their tendency to offer the intervention to patients. No structural factors were found to be positively associated with selective provision. Patient and nurse factors contributed to the selective provision of a brief intervention in primary care. If

  1. Water Demand Management Policy Brief No

    International Development Research Centre (IDRC) Digital Library (Canada)

    Bob Stanley

    Fair share: Water Demand Management can help provide fair access to water for the poor. Water Policy. Brief no.2 ... management (WDM) can help spread water more equitably, providing a measure of opportunity, security and ... improving health and quality of life for families. WDM measures can improve the efficiency of.

  2. Brief Interventions in the Treatment of Alcohol Use Disorders: Definition and Overview.

    Science.gov (United States)

    Osburn, Cynthia J.

    2001-01-01

    Reviews the literature and describes the nature and feasibility of brief interventions in the treatment of alcohol use disorders. Attention is given to the promising results of outcome studies, and recommendations are provided for the implementation of brief interventions with a heterogeneous clientele. (Contains 39 references.) (GCP)

  3. Brief International Cognitive Assessment for MS (BICAMS): international standards for validation.

    OpenAIRE

    Benedict, R; Amato, Mp; Boringa, J; Brochet, B; Foley, F; Fredrikson, S; Hamalainen, P; Hartung, H; Krupp, L; Penner, I; Reder, A; Langdon, D.

    2012-01-01

    An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different langu...

  4. Paulus as vredemaker. Oor die resepsie van die Brief aan Filemon ...

    African Journals Online (AJOL)

    7 Jul 2015 ... Inleiding. Die woord 'vrede' kom net een maal in die Filemonbrief voor, en wel in die aanhef van die brief. Kommentatore merk egter gereeld op dat 'n mens nie daaruit moet aflei dat dié begrip onbelangrik vir die verstaan van die brief is nie. Om een voorbeeld te noem: Barth en Blanke. (2002) skryf as volg:.

  5. DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme

    Science.gov (United States)

    Yang, Jian-kai; Song, Jian; Huo, Hao-ran; Zhao, Yin-long; Zhang, Guang-yu; Zhao, Zong-mao; Sun, Guo-zhu; Jiao, Bao-hua

    2017-01-01

    Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM. PMID:29449895

  6. Interagency advanced power group: Semi-annual compilation of briefs, March 1993

    International Nuclear Information System (INIS)

    1993-03-01

    The Government Research and Development Summaries now available from NTIS are project briefs prepared by the Interagency Advanced Power Group (IAPG). They describe the status of all programs in the fields of advanced power research, development and engineering. Members of the IAPG are the U.S. Army, Navy, and Air Force, U.S. Department of Energy and the National Aeronautics and Space Administration (NASA). Their cooperative effort monitors government-funded research and development producing project briefs in the following working groups: Chemical; Electrical; Magnetohydrodynamic; Mechanical, Nuclear, TE, TI; Solar; and Systems. Each project brief contains title; project description; contract number, period, probable completion date and funding; principle investigator name and telephone number; contractor name and address; directing agency; and index terms

  7. The Wage Gap: Briefing Paper #1.

    Science.gov (United States)

    National Committee on Pay Equity, Washington, DC.

    Women have made slow, steady progress in the labor market since 1979, but the wage gap has not narrowed significantly. This briefing paper updates a September 1987 paper based on "Male-Female Differences in Work Experience, Occupations, and Earnings: 1984" (Current Population Reports, Household Economic Studies, Series P-70, No. 10, issued in…

  8. Brief review of Planck law

    International Nuclear Information System (INIS)

    Zamora Carranza, M.

    2001-01-01

    This paper presents a brief review of the scientific events which led to the determination of the law of radiation and the quantisation of energy by Max Planck. From the separation of sunlight by Newton to the reasons which led Planck to quantised the energy of an oscillator. I discuss the theoretical and experimental difficulties which scientists overcame to derive the law of heat radiation. (Author) 6 refs

  9. Economic Education in Malaysia: A Brief Report.

    Science.gov (United States)

    Rao, C. A.

    1978-01-01

    This report provides a brief description of economic education in Malaysia and indicates interest, on the part of various Asian countries, i.e., Malaysia, Singapore, Indonesia, Thailand, and the Philippines, in the establishment of economic education programs. (Editor/RK)

  10. From efficacy to effectiveness and beyond: what next for brief interventions in primary care?

    Directory of Open Access Journals (Sweden)

    Amy eO'Donnell

    2014-08-01

    Full Text Available Background: Robust evidence supports the effectiveness of screening and brief alcohol interventions in primary healthcare. However lack of understanding about their ‘active ingredients’ and concerns over the extent to which current approaches remain faithful to their original theoretical roots, has led some to demand a cautious approach to future roll-out pending further research. Against this background, this paper provides a timely overview of the development of the brief alcohol intervention evidence base in order to assess the extent to which it has achieved the four key levels of intervention research: efficacy; effectiveness; implementation; and demonstration.Methods: Narrative overview based on:(1 results of a review of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare;(2 synthesis of the findings of key additional primary studies on the improvement and evaluation of brief alcohol intervention implementation in routine primary healthcare.Results: The brief intervention field seems to constitute an almost perfect example of the evaluation of a complex intervention. Early evaluations of screening and brief intervention approaches included more tightly controlled efficacy trials and have been followed by more pragmatic trials of effectiveness in routine clinical practice. Most recently, attention has shifted to dissemination, implementation and wider-scale roll-out. However, delivery in routine primary health remains inconsistent, with an identified knowledge gap around how to successfully embed brief alcohol intervention approaches in mainstream care, and as yet unanswered questions concerning what specific intervention component prompt the positive changes in alcohol consumption.Conclusion: Both the efficacy and effectiveness of brief alcohol interventions have been comprehensively demonstrated, and intervention effects seem replicable and stable over time, and across

  11. Flexible Design and Operation of a Smart Charging Microgrid (Briefing Charts)

    Science.gov (United States)

    2014-04-08

    release; distribution unlimited 13. SUPPLEMENTARY NOTES Briefing Charts for SAE World Congress 2014 14. ABSTRACT A microgrid is a controllable ...UNCLASSIFIED Distribution Statement A: Approved for Public Release Flexible Design and Operation of a Smart Charging Microgrid Annette G... control number. 1. REPORT DATE 08 APR 2014 2. REPORT TYPE Briefing Charts 3. DATES COVERED 08-01-2014 to 09-03-2014 4. TITLE AND SUBTITLE

  12. Response to: Brief Comments on “Siddhis and Psi Research: An Interdisciplinary Analysis”

    Directory of Open Access Journals (Sweden)

    SONALI BHATT MARWAHA

    2017-06-01

    Full Text Available In his brief comments on “Siddhis and Psi Research: An Interdisciplinary Analysis,” Ed Kelly expresses disappointment that the paper does not mirror his worldview, which includes questioning the reality of psi—especially precognition, accepting post-mortem survival and observational evidence for macro-PK including levitation. In this brief response to Kelly, I provide arguments in support of informational psi, particularly precognition, and in favor of a physicalist, signal-based approach to psi, with brief points against the validity of micro-PK (mind-over-matter and post-mortem survival.

  13. Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

    OpenAIRE

    Gu, Bobby; Magil, Alex B.; Barbour, Sean J.

    2016-01-01

    Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody?positive flares with pulmonary and renal involvement, and anti-GBM antibody?negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over...

  14. Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up

    Directory of Open Access Journals (Sweden)

    Eleni Loukianou

    2010-05-01

    Full Text Available Eleni Loukianou, Dimitrios Brouzas, Eleni Georgopoulou, Chrysanthi Koutsandrea, Michael ApostolopoulosEye Department, University of Athens, Athens, GreecePurpose: To evaluate the safety and efficacy of intravitreal injections of bevacizumab (Avastin® as a treatment option for radiation maculopathy secondary to proton beam radiotherapy for choroidal melanoma.Case: A 61-year-old woman presented with a gradual decrease in left eye visual acuity (VA 29 months after proton beam radiotherapy for choroidal melanoma. On presentation, her best-corrected VA (BCVA was 2/10 in the left eye and the intraocular pressure was 15 mmHg. Fundoscopy revealed cystoid macular edema, intraretinal hemorrhages, epiretinal membrane in the posterior pole, and residual tumor scar with exudative retinal detachment and hard exudates in the periphery of the superotemporal quadrant. A treatment with intravitreal injections of bevacizumab (Avastin® was recommended. The injections were performed on a six-weekly basis.Results: The central retinal thickness prior to the treatment was 458 μm. After the first intravitreal injection of bevacizumab, the retinal thickness at the centre of the fovea was reduced to 322 μm. After the third injection, the central retinal thickness was 359 μm and 18 months after presentation, it reduced to 334 μm. The BCVA increased to 3/10 after the intravitreal injections of bevacizumab and remained stable during the follow-up period. The intraocular pressure was within normal range during the follow-up period.Conclusion: Bevacizumab should be regarded as a treatment option for macular edema due to proton beam radiotherapy for choroidal melanoma. By reducing the central retinal thickness, intravitreal bevacizumab can improve VA or ameliorate further decline caused by radiation maculopathy.Keywords: bevacizumab (Avastin®, choroidal melanoma, macular edema, radiation retinopathy

  15. Universities and Development: Global Cooperation. Policy Briefing

    Science.gov (United States)

    Universities UK, 2010

    2010-01-01

    This policy briefing aims to demonstrate that universities are key organisations in international development. Universities are involved in a wide range of international development activities, including collaborative research projects, developing entrepreneurial and employability skills and the evaluation of non-governmental organisation (NGO)…

  16. NASA Ames Fluid Mechanics Laboratory research briefs

    Science.gov (United States)

    Davis, Sanford (Editor)

    1994-01-01

    The Ames Fluid Mechanics Laboratory research program is presented in a series of research briefs. Nineteen projects covering aeronautical fluid mechanics and related areas are discussed and augmented with the publication and presentation output of the Branch for the period 1990-1993.

  17. A brief history of the philosophy of time

    CERN Document Server

    Bardon, Adrian

    2013-01-01

    Adrian Bardon's A Brief History of the Philosophy of Time is a short introduction to the history, philosophy, and science of the study of time-from the pre-Socratic philosophers through Einstein and beyond. A Brief History of the Philosophy of Time covers subjects such as time and change, the experience of time, physical and metaphysical approaches to the nature of time, the direction of time, time travel, time and freedom of the will, and scientific and philosophical approaches to eternity and the beginning of time. Bardon employs helpful illustrations and keeps technical language to a minimum in bringing the resources of over 2500 years of philosophy and science to bear on some of humanity's most fundamental and enduring questions.

  18. Brief report: The Brief Alcohol Social Density Assessment (BASDA): convergent, criterion-related, and incremental validity.

    Science.gov (United States)

    MacKillop, James; Acker, John D; Bollinger, Jared; Clifton, Allan; Miller, Joshua D; Campbell, W Keith; Goodie, Adam S

    2013-09-01

    Alcohol misuse is substantially influenced by social factors, but systematic assessments of social network drinking are typically lengthy. The goal of the present study was to provide further validation of a brief measure of social network alcohol use, the Brief Alcohol Social Density Assessment (BASDA), in a sample of emerging adults. Specifically, the study sought to examine the BASDA's convergent, criterion, and incremental validity in relation to well-established measures of drinking motives and problematic drinking. Participants were 354 undergraduates who were assessed using the BASDA, the Alcohol Use Disorders Identification Test (AUDIT), and the Drinking Motives Questionnaire. Significant associations were observed between the BASDA index of alcohol-related social density and alcohol misuse, social motives, and conformity motives, supporting convergent validity. Criterion-related validity was supported by evidence that significantly greater alcohol involvement was present in the social networks of individuals scoring at or above an AUDIT score of 8, a validated criterion for hazardous drinking. Finally, the BASDA index was significantly associated with alcohol misuse above and beyond drinking motives in relation to AUDIT scores, supporting incremental validity. Taken together, these findings provide further support for the BASDA as an efficient measure of drinking in an individual's social network. Methodological considerations as well as recommendations for future investigations in this area are discussed.

  19. Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation.

    Science.gov (United States)

    Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

    2014-12-01

    Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. © The Author(s) 2014

  20. Advanced Public Transportation Systems. Technical Assistance Brief 2

    Science.gov (United States)

    1993-01-01

    The Advanced Public Transportation Systems (APTS) Program requires evaluation : of pilot projects. This technical assistance brief discusses the guidelines set : for developing evaluation framework and methodology for local projects. 4p.

  1. Mesothelin as a novel biomarker and immunotherapeutic target in human glioblastoma

    DEFF Research Database (Denmark)

    Liu, Zhenjiang; Rao, Martin; Poiret, Thomas

    2017-01-01

    Glioblastoma multiforme (GBM) presents the most malignant form of glioma, with a 5-year survival rate below 3% despite standard therapy. Novel immune-based therapies in improving treatment outcomes in GBM are therefore warranted. Several molecularly defined targets have been identified mediating...... anti-GBM cellular immune responses. Mesothelin is a tumor-associated antigen (TAA) which is expressed in several solid tumors with different histology. Here, we report the immunological significance of mesothelin in human malignant glioma. Expression of mature, surface-bound mesothelin protein...... was found to bein human GBM defined by immunofluorescence microscopy, and on freshly isolated, single cell suspension of GBM tumor cells and GBM tumor cell lines, determined by based on flow cytometric analysis. Peripheral blood (PB) from patients with GBM, stimulated with mesothelin peptides and IL-2, IL...

  2. The ACT and SAT: No Longer Just College Admission Tests. Policy Brief

    Science.gov (United States)

    Hite, Jenny; Lord, Joan

    2014-01-01

    This brief report offers analysis of ACT and SAT results from 2008 to 2013 in the Southern Regional Education Board (SREB) region. The brief focuses on the increase in test participation rates and points to policies that SREB states initiated that affected these rates. Five SREB states currently require 100 percent student participation on the…

  3. An Event Observed as a Terrestrial Gamma-ray Flash (TGF) and a Terrestrial Electron Beam (TEB) by Fermi GBM

    Science.gov (United States)

    Stanbro, M.; Briggs, M. S.; Cramer, E.; Dwyer, J. R.; Roberts, O.

    2017-12-01

    Terrestrial Gamma-ray Flashes (TGFs) are sub-ms, intense flashes of gamma-rays. They are due to the acceleration of electrons with relativistic energies in thunderstorms that emit gamma-rays via bremsstrahlung. When these photons reach the upper atmosphere, they can produce secondary electrons and positrons that escape the atmosphere and propagate along the Earth's magnetic field line. Space instruments can detect these charged particles, known as Terrestrial Electron Beams (TEBs), after traveling thousands of kilometers from the thunderstorm. We present an event that was observed by the Fermi Gamma-ray Burst Monitor (GBM) as both a TGF and a TEB. To our knowledge this is the first such event that has ever been observed. We interpret the first pulse as a TGF with a duration of 0.2 ms. After 0.5 ms a second pulse is seen with a duration of 2 ms that we interpret as a TEB. Confirming this interpretation, a third pulse is seen 90 ms later, which is understood as a TEB magnetic mirror pulse. The World Wide Lightning Location Network (WWLLN) and the Earth Networks Total Lightning Network (ENTLN) detected a sferic, under the spacecraft footprint and within the southern magnetic footprint that is simultaneous with the first pulse. Along with the sferic, this unique observation allows us for the first time to test TGF and TEB models for the same event. We present Monte Carlo simulations of the first two pulses, including pitch angles for electrons and positrons, to see if the models can consistently describe the TGF/TEB spectra and time profiles originating from the same source.

  4. Identification of repaglinide as a therapeutic drug for glioblastoma multiforme

    International Nuclear Information System (INIS)

    Xiao, Zui Xuan; Chen, Ruo Qiao; Hu, Dian Xing; Xie, Xiao Qiang; Yu, Shang Bin; Chen, Xiao Qian

    2017-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients. - Highlights: • Gene expression signarue in long-term survived GBM patients are identified from Gene Expression Omnibus database. • Repaglinide is identified as a survival-related drug for GBM via drug repositioning in CMap. • Repaglinide effectively kills GBM cells, inhibits GBM cell migration and increases survival of mice bearing orthotopic glioma. • Repaglinide reduces Bcl-2, Beclin-1 and PD-L1 in GBM tissues.

  5. Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study.

    Science.gov (United States)

    Brooks, Ronald A; Landovitz, Raphael J; Kaplan, Rachel L; Lieber, Eli; Lee, Sung-Jae; Barkley, Thomas W

    2012-02-01

    The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.

  6. 1. A brief history of nuclear medicine

    International Nuclear Information System (INIS)

    Dienstbier, Z.

    1989-01-01

    The milestones of history of nuclear medicine are dealt with. A brief account is given of the history of nuclear medicine abroad, and a more in-depth treatment is devoted to Czechoslovakia, where the beginning of this branch of science dates to 1951. (Z.S.)

  7. Testicular Embryonic Rhabdomyosarcoma, Case report with brief ...

    African Journals Online (AJOL)

    Testicular Embryonic Rhabdomyosarcoma, Case report with brief literature review. AM Adam, MMAM Ibnouf, IAF Allah. Abstract. Background: Rhabdomyosarcoma (RMS) is a malignant solid tumour arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites.

  8. Brief mindfulness meditation training alters psychological and neuroendocrine responses to social evaluative stress.

    Science.gov (United States)

    Creswell, J David; Pacilio, Laura E; Lindsay, Emily K; Brown, Kirk Warren

    2014-06-01

    To test whether a brief mindfulness meditation training intervention buffers self-reported psychological and neuroendocrine responses to the Trier Social Stress Test (TSST) in young adult volunteers. A second objective evaluates whether pre-existing levels of dispositional mindfulness moderate the effects of brief mindfulness meditation training on stress reactivity. Sixty-six (N=66) participants were randomly assigned to either a brief 3-day (25-min per day) mindfulness meditation training or an analytic cognitive training control program. All participants completed a standardized laboratory social-evaluative stress challenge task (the TSST) following the third mindfulness meditation or cognitive training session. Measures of psychological (stress perceptions) and biological (salivary cortisol, blood pressure) stress reactivity were collected during the social evaluative stress-challenge session. Brief mindfulness meditation training reduced self-reported psychological stress reactivity but increased salivary cortisol reactivity to the TSST, relative to the cognitive training comparison program. Participants who were low in pre-existing levels of dispositional mindfulness and then received mindfulness meditation training had the greatest cortisol reactivity to the TSST. No significant main or interactive effects were observed for systolic or diastolic blood pressure reactivity to the TSST. The present study provides an initial indication that brief mindfulness meditation training buffers self-reported psychological stress reactivity, but also increases cortisol reactivity to social evaluative stress. This pattern may indicate that initially brief mindfulness meditation training fosters greater active coping efforts, resulting in reduced psychological stress appraisals and greater cortisol reactivity during social evaluative stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. How Gene-Environment Interaction Affects Children's Anxious and Fearful Behavior. Science Briefs

    Science.gov (United States)

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Evidence for a Gene-Environment Interaction in Predicting Behavioral Inhibition in Middle Childhood" (N. A. Fox, K E. Nichols, H. A. Henderson, K. Rubin, L. Schmidt, D. Hamer, M. Ernst, and D. S.…

  10. What Is Evidence-Based Practice? Research-to-Results Brief. Publication #2007-14

    Science.gov (United States)

    Metz, Allison J. R.; Espiritu, Rachele; Moore, Kristin A.

    2007-01-01

    This brief represents part 1 in a series on fostering the adoption of evidence-based practices in out-of-school time programs. The lag between discovering effective practices and using them "on the ground" can be unnecessarily long, sometimes taking 15 to 20 years! The purpose of this brief is to provide practitioners with a better understanding…

  11. Brief communication: Low prevalence of HIV infection, and ...

    African Journals Online (AJOL)

    Brief communication: Low prevalence of HIV infection, and knowledge, ... History of sexually transmitted diseases was reported by 10.7% of the sexually active students. ... Continued health education is needed to bring behavioral changes.

  12. Brief introduction about radiation hygiene in Russian navy

    International Nuclear Information System (INIS)

    Li Yu; Min Rui; Pan Zhen

    2005-01-01

    During long-time radiation working practice, there have been established comprehensive radiation hygiene system of technique and regulation in Russian navy. Brief introduction about radiation hygiene in Russian navy are as follows. (authors)

  13. Brief Assessment of Krsko NPP Decommissioning Costs

    International Nuclear Information System (INIS)

    Skanata, D.; Medakovic, S.; Debrecin, N.

    2000-01-01

    The first part of the paper gives a brief description of decommissioning scenarios and models of financing the decommissioning of NPPs. The second part contains a review of decommissioning costs for certain PWR plants with a brief description of methods used for that purpose. The third part of the paper the authors dedicated to the assessment of decommissioning costs for Krsko NPP. It does not deal with ownership relations and obligations ensuing from them. It starts from the simple point that decommissioning is an structure of the decommissioning fund is composed of three basic cost items of which the first refers to radioactive waste management, the second to storage and disposal of the spent nuclear fuel and the third to decommissioning itself. The assessment belongs to the category of preliminary activities and as such has a limited scope and meaning. Nevertheless, the authors believe that it offers a useful insight into the basic costs that will burden the decommissioning fund of Krsko NPP. (author)

  14. Usability Briefing - a process model for healthcare facilities

    DEFF Research Database (Denmark)

    Fronczek-Munter, Aneta

    2014-01-01

    Background: In complex buildings with many types of users it can be difficult to satisfy the numerous, often contradictory requirements. Research in usability mostly focuses on evaluating products or facilities with users, after they were built. This paper is part of a PhD project “Usability...... with various users/stakeholders, using creative boundary objects at workshops.  Practical Implications: The research results have relevance to researchers, client organisations, facility managers and architects planning new complex facilities.  Research limitations: The proposed model is theoretical and needs...... briefing for hospitals”, where methods for capturing user needs and experiences at hospital facilities are investigated in order to feed into design processes and satisfy the users’ needs and maximise the effectiveness of facilities. Purpose: This paper introduces the concept of usability briefing...

  15. Brief strategic therapy in patients with social phobia with or without personality disorder.

    Science.gov (United States)

    Rakowska, Jadwiga Malgorzata

    2011-07-01

    The aim of this study was to test the effects of brief strategic therapy in people with social phobia distinguished by the presence or absence of DSM anxious personality disorder. A group of 120 outpatients with social phobia, 60 of them with comorbid DSM anxious personality disorder, were randomly assigned to 10 weeks of brief strategic therapy or minimal supportive therapy. Outcome analyses were conducted on the intent-to-treat sample at posttreatment and 3-month follow-up using self-report interpersonal sensitivity and phobic anxiety measures, and at 6-month follow-up using social phobia diagnostic status. Brief strategic therapy was superior to minimal supportive therapy in patients with social phobia only. It was not significantly better in patients with comorbid personality disorder. It was concluded that 10 weeks of brief strategic therapy shows promise as a cost-effective method for management of social phobia. It has limited value as a method for management of social phobia with personality disorder.

  16. High-energy emission from bright gamma-ray bursts using Fermi

    Energy Technology Data Exchange (ETDEWEB)

    Bissaldi, Elisabetta

    2010-05-25

    Among the scientific objectives of one of the present NASA missions, the Fermi Gamma-ray Space Telescope (FGST), is the study of gamma-ray bursts (GRBs). Fermi's payload comprises two science instruments, the Large Area Telescope (LAT) and the Gamma-Ray Burst Monitor (GBM). GBM was designed to detect and localize bursts for the Fermi mission. By means of an array of 12 NaI(Tl) (8 keV to 1 MeV) and two BGO (0.2 to 40 MeV) scintillation detectors, GBM extends the energy range (20 MeV to > 300 GeV) of the LAT instrument into the traditional range of current GRB databases. The physical detector response of the GBM instrument to GRBs has been determined with the help of Monte Carlo simulations, which are supported and verified by on-ground individual detector calibration measurements. The GBM detectors have been calibrated from 10 keV to 17.5 MeV using various gamma sources, and the detector response has been derived by simulations over the entire energy range (8 keV to 40 MeV) using GEANT. The GBM instrument has been operating successfully in orbit since June 11, 2008. The total trigger count from the time GBM triggering was enabled in July 2008 through December 2009 is 655, and about 380 of these triggers were classified as GRBs. Moreover, GBM detected several bursts in common with the LAT. These amazing detections mainly fulfill the primary science goal of GBM, which is the joint analysis of spectra and time histories of GRBs observed by both Fermi instruments. For every trigger, GBM provides near-real time on-board burst locations to permit repointing of the spacecraft and to obtain LAT observations of delayed emission from bursts. GBM and LAT refined locations are rapidly disseminated to the scientific community, often permitting extensive multiwavelength follow-up observations by NASA's Swift mission or other space- based observatories, and by numerous ground-based telescopes, thus allowing redshift determinations. Calculations of LAT upper limits are

  17. High-energy emission from bright gamma-ray bursts using Fermi

    International Nuclear Information System (INIS)

    Bissaldi, Elisabetta

    2010-01-01

    Among the scientific objectives of one of the present NASA missions, the Fermi Gamma-ray Space Telescope (FGST), is the study of gamma-ray bursts (GRBs). Fermi's payload comprises two science instruments, the Large Area Telescope (LAT) and the Gamma-Ray Burst Monitor (GBM). GBM was designed to detect and localize bursts for the Fermi mission. By means of an array of 12 NaI(Tl) (8 keV to 1 MeV) and two BGO (0.2 to 40 MeV) scintillation detectors, GBM extends the energy range (20 MeV to > 300 GeV) of the LAT instrument into the traditional range of current GRB databases. The physical detector response of the GBM instrument to GRBs has been determined with the help of Monte Carlo simulations, which are supported and verified by on-ground individual detector calibration measurements. The GBM detectors have been calibrated from 10 keV to 17.5 MeV using various gamma sources, and the detector response has been derived by simulations over the entire energy range (8 keV to 40 MeV) using GEANT. The GBM instrument has been operating successfully in orbit since June 11, 2008. The total trigger count from the time GBM triggering was enabled in July 2008 through December 2009 is 655, and about 380 of these triggers were classified as GRBs. Moreover, GBM detected several bursts in common with the LAT. These amazing detections mainly fulfill the primary science goal of GBM, which is the joint analysis of spectra and time histories of GRBs observed by both Fermi instruments. For every trigger, GBM provides near-real time on-board burst locations to permit repointing of the spacecraft and to obtain LAT observations of delayed emission from bursts. GBM and LAT refined locations are rapidly disseminated to the scientific community, often permitting extensive multiwavelength follow-up observations by NASA's Swift mission or other space- based observatories, and by numerous ground-based telescopes, thus allowing redshift determinations. Calculations of LAT upper limits are mainly based

  18. Decreased memory loss associated with right unilateral ultra-brief pulse wave ECT.

    Science.gov (United States)

    Kim, Suck Won; Grant, Jon E; Rittberg, Barry R; Simon, John E; Vine, Craig J; Schulz, S Charles

    2007-01-01

    The purpose of this brief article is to share with our colleagues in the psychiatric community and other physicians information about the efficacy of an emerging new method of electroconvulsive therapy (ECT) that shows advantages over existing treatments for depression. Patients treated with the method, ultra-brief pulse wave ECT, have less memory loss and confusion than those treated with longer-duration ECT.

  19. Immunological targeting of cytomegalovirus for glioblastoma therapy

    OpenAIRE

    Nair, Smita K; Sampson, John H; Mitchell, Duane A

    2014-01-01

    Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.

  20. Center for Information Systems Research Research Briefings 2002

    OpenAIRE

    ROSS, JEANNE W.

    2003-01-01

    This paper is comprised of research briefings from the MIT Sloan School of Management's Center for Information Systems Research (CISR). CISR's mission is to perform practical empirical research on how firms generate business value from IT.

  1. Transmitter-controlled properties of α-motoneurones causing long-lasting motor discharge to brief excitatory inputs

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Kiehn, O.

    1986-01-01

    Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced ...... flipflops, which are set at one of two levels by short excitatory or inhibitory inputs. However, when the whole motoneuronal pool is considered, many different levels can be maintained by recruitment of new units.......Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced...

  2. Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

    Science.gov (United States)

    Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

  3. Qualitative examination of enacted stigma towards gay and bisexual men and related health outcomes in Tajikistan, Central Asia.

    Science.gov (United States)

    Ibragimov, Umedjon; Wong, Frank Y

    2018-05-01

    Gay and bisexual men (GBM) in Tajikistan are an extremely stigmatised group at high risk for sexually transmitted infections and HIV. However, there is a paucity of research on how and in what way stigma affects their lives. We conducted a qualitative study to examine the impact of stigma on GBM's lives in Tajikistan, focusing on stigma enactors, settings, factors affecting vulnerability of GBM and health consequences. Eight individual in-depth interviews and 3 focus-group discussions with 13 participants (N   =   21) from GBM community were conducted in two cities of Tajikistan. Results reveal that police frequently engage in blackmail and perpetrate sexual and physical violence against GBM. Service providers often discriminate against GBM limiting their access to health and legal services. Exposure to stigma results in chronic stress affecting mental health of GBM. Fear of disclosure, low social cohesion, absence of prominent opinion leaders and activists reduce resilience of GBM community to stigma. State-sanctioned violations of human rights of marginalised populations and lack of effective legal protection mechanisms have enabled widespread harassment of GBM. These findings warrant further research on stigma leading to the development of culturally adapted and tailored multilevel structural interventions, including broad legal and policy reforms.

  4. Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.

    Science.gov (United States)

    Yang, Bo; Heng, Liang; Du, Shuli; Yang, Hua; Jin, Tianbo; Lang, Hongjun; Li, Shanqu

    2015-07-09

    Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. Using the χ(2) test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes "CC" of rs2297440 and "GG" of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population.

  5. Enjoying food without caloric cost: The impact of brief mindfulness on laboratory eating outcomes.

    Science.gov (United States)

    Arch, Joanna J; Brown, Kirk Warren; Goodman, Robert J; Della Porta, Matthew D; Kiken, Laura G; Tillman, Shanna

    2016-04-01

    Mindfulness-based interventions have been increasingly applied to treat eating-related problems ranging from obesity to eating disorders. Yet few studies have empirically examined the mechanisms of a mindful approach to eating. The current studies examine the potential of brief mindfulness instructions to enhance the psychological and behavioral dimensions of eating. In three experiments (total N = 319 undergraduates), we examined whether brief mindfulness instructions would enhance the positive sensory experience involved in tasting food as well as healthy eating behaviors. Relative to distraction control instructions, the first two studies demonstrated that brief mindfulness instructions increased the enjoyment of a commonly pleasurable food (chocolate; Study 1), and a food with generally more mixed associations (raisins; Study 2). The third study replicated and extended these findings to show that brief mindfulness instructions also led to lower calorie consumption of unhealthy food relative to distracted or no-instruction control conditions, an effect mediated by greater eating enjoyment. Findings demonstrated the power of brief mindfulness instructions to positively impact both health-relevant behavior and sensory experience associated with eating food. Implications for both theory and clinical applications of mindfulness are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Research and development at Kernforschungszentrum Karlsruhe - brief report 1991

    International Nuclear Information System (INIS)

    1992-01-01

    Research at Kernforschungszentrum Karlsruhe in the nineties is focussed on environmentally compatible high technologies with emphasis on environmental engineering, power engineering, microsystems technology, and selected fields of fundamental research. The KfK research and development trends are reflected by this brief report. The facts and figures inform researchers and specialists by summarizing the major results of the current research projects and by informing about the main targets and trends of long-time research programs and individual projects. The brief reports are completed by comprehensive, annual progress reports which discuss the implementation and results of the KfK research activities and compile references which list the various scientifico-technical reports, contributions to journals, conference papers, and other publications. (orig.) [de

  7. Studying Child Care Subsidies with Secondary Data Sources. Methodological Brief OPRE 2012-54

    Science.gov (United States)

    Ha, Yoonsook; Johnson, Anna D.

    2012-01-01

    This brief describes four national surveys with data relevant to subsidy-related research and provides a useful set of considerations for subsidy researchers considering use of secondary data. Specifically, this brief describes each of the four datasets reviewed, highlighting unique features of each dataset and providing information on the survey…

  8. Download How to write a policy brief

    International Development Research Centre (IDRC) Digital Library (Canada)

    Francine Bouchard

    Do a SWOT analysis – what are the strengths, weaknesses, opportunities and threats surrounding the research issue. Executive Summary. A one or two sentence overview of the brief that entices readers to go further. Introduction. Answer the question why is the topic important, why should people care. Answer the question ...

  9. Counseling Services and Student Success. Research Brief

    Science.gov (United States)

    Francis, Perry C.; Horn, Aaron S.

    2016-01-01

    The purpose of this research brief is to provide an overview of mental health issues and counseling services on college campuses. The findings from several national surveys are reviewed to estimate the prevalence of anxiety and depression, suicide and suicidal ideation, and violence among college students. Common prevention and treatment programs…

  10. A Brief History of the Flathead Tribes.

    Science.gov (United States)

    Woodcock, Clarence; And Others

    A source document, illustrated with many black and white photographs of tribe members and activities, provides a brief history of the American Indian tribes, now called the Flatheads, living on the Flathead Indian Reservation in Montana and describes some of their cultural traditions, particularly their ceremonial dances. The booklet traces the…

  11. Early Learning and Educational Technology Policy Brief

    Science.gov (United States)

    Lee, Joan

    2016-01-01

    Recognizing the growth of technology use in early learning settings, the U.S. Department of Education and U.S. Department of Health and Human Services collaborated in the development of the "Early Learning and Educational Technology Policy Brief" to promote developmentally appropriate use of technology in homes and early learning…

  12. Professional Development: Focusing on Transition. Issue Brief

    Science.gov (United States)

    de Azúa, Ramón L.; Keleher, Julia

    2017-01-01

    In 2017, the National Technical Assistance Center for the Education of Neglected or Delinquent Children and Youth (NDTAC) released its first in a series of professional development briefs that focus on the professional development needs and interests of Neglected or Delinquent (N or D) State coordinators, correctional educators, and providers of…

  13. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.

    Science.gov (United States)

    Groffen, A J; Ruegg, M A; Dijkman, H; van de Velden, T J; Buskens, C A; van den Born, J; Assmann, K J; Monnens, L A; Veerkamp, J H; van den Heuvel, L P

    1998-01-01

    Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

  14. Large Intergenic Non-coding RNA-RoR Inhibits Aerobic Glycolysis of Glioblastoma Cells via Akt Pathway

    Science.gov (United States)

    Li, Yong; He, Zhi-Cheng; Liu, Qing; Zhou, Kai; Shi, Yu; Yao, Xiao-Hong; Zhang, Xia; Kung, Hsiang-Fu; Ping, Yi-Fang; Bian, Xiu-Wu

    2018-01-01

    Reprogramming energy metabolism is a hallmark of malignant tumors, including glioblastoma (GBM). Aerobic glycolysis is often utilized by tumor cells to maintain survival and proliferation. However, the underlying mechanisms of aerobic glycolysis in GBM remain elusive. Herein, we demonstrated that large intergenic non-coding RNA-RoR (LincRNA-RoR) functioned as a critical suppressor to inhibit the aerobic glycolysis and viability of GBM cells. We found that LincRNA-RoR was markedly reduced in GBM tissues compared with adjacent non-tumor tissues from 10 cases of GBM patients. Consistently, LincRNA-RoR expression in GBM cells was significantly lower than that in normal glial cells. The aerobic glycolysis of GBM cells, as determined by the measurement of glucose uptake and lactate production, was impaired by LincRNA-RoR overexpression. Mechanistically, LincRNA-RoR inhibited the expression of Rictor, the key component of mTORC2 (mammalian target of rapamycin complex 2), to suppress the activity of Akt pathway and impair the expression of glycolytic effectors, including Glut1, HK2, PKM2 and LDHA. Finally, enforced expression of LincRNA-RoR reduced the proliferation of GBM cells in vitro, restrained tumor growth in vivo, and repressed the expression of glycolytic molecules in GBM xenografts. Collectively, our results underscore LincRNA-RoR as a new suppressor of GBM aerobic glycolysis with therapeutic potential. PMID:29581766

  15. Sharing information: Mixed-methods investigation of brief experiential interprofessional

    Science.gov (United States)

    Cocksedge, Simon; Barr, Nicky; Deakin, Corinne

    In UK health policy ‘sharing good information is pivotal to improving care quality, safety, and effectiveness. Nevertheless, educators often neglect this vital communication skill. The consequences of brief communication education interventions for healthcare workers are not yet established. This study investigated a three-hour interprofessional experiential workshop (group work, theoretical input, rehearsal) training healthcare staff in sharing information using a clear structure (PARSLEY). Staff in one UK hospital participated. Questionnaires were completed before, immediately after, and eight weeks after training, with semistructured interviews seven weeks after training. Participants (n=76) were from assorted healthcare occupations (26% non-clinical). Knowledge significantly increased immediately after training. Self-efficacy, outcome expectancy, and motivation to use the structure taught were significantly increased immediately following training and at eight weeks. Respondents at eight weeks (n=35) reported their practice in sharing information had changed within seven days of training. Seven weeks after training, most interviewees (n=13) reported confidently using the PARSLEY structure regularly in varied settings. All had re-evaluated their communication practice. Brief training altered self-reported communication behaviour of healthcare staff, with sustained changes in everyday work. As sharing information is central to communication curricula, health policy, and shared decision-making, the effectiveness of brief teaching interventions has economic and educational implications.

  16. A randomized trial of a brief intervention for obesity in college students.

    Science.gov (United States)

    Buscemi, J; Yurasek, A M; Dennhardt, A A; Martens, M P; Murphy, J G

    2011-08-01

    •  Brief motivational interventions have been found to be efficacious for obesity in older adult populations. •  Brief motivational interventions including delivery of personalized feedback have been found to be efficacious for reducing college student drinking. •  First study to test the efficacy of a one-session, brief motivational intervention for obesity among college students. •  One session brief motivational interventions may have an impact on the reduction of calorie-dense foods and beverages. •  A brief, one-session motivational interview with personalized feedback may not be an intensive enough intervention for obesity treatment among college students. Young adults are at an increased risk for weight gain as they begin college and this has implications for the onset of future health consequences. Brief motivational interventions (BMIs) have been found to be effective with college students for reducing risky health behaviours such as alcohol consumption, but have not been developed and tested with a primary goal of reducing obesity. BMIs have been developed and tested for the treatment of obesity and weight-related health behaviours (WRHB) in other populations, such as adults and adolescents, with promising results. The purpose of the following study was to develop and test the efficacy of a BMI for weight loss among overweight and obese college students. Seventy undergraduate students (85.7% female, 57.1% African-American) completed an assessment about WRHBs and then were randomized to either receive a single 60-min BMI plus a booster phone call or to assessment only. At 3 months post-intervention, effect sizes within the intervention group were twice as large as within the assessment-only group on reductions in high-calorie foods and beverages. However, there were no statistically significant differences between groups on body mass index or WRHBs. The one-session nature of the session might not have been enough to produce

  17. PISA for Development and the Sustainable Development Goals. PISA for Development Brief 17

    Science.gov (United States)

    OECD Publishing, 2017

    2017-01-01

    The PISA for Development brief series is a set of concise monthly education policy-oriented notes published by the OECD which are designed to describe a specific PISA for Development topic. In this brief, PISA's role in monitoring the fourth United Nations Sustainable Development Goal--to "ensure inclusive and equitable quality education and…

  18. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  19. ENVIRONMENTAL RESEARCH BRIEF: THERMOPHYSICAL PROPERTIES OF HFE-125

    Science.gov (United States)

    Thermophysical properties of HFE-125 (pentafluorodimethylether) suggest that it could serve as an alternative non-ozone depleting refrigerant for certain low temperature applications. This Brief presents the thermophysical properties of HFE-125 (Tables 1-4) which have been obtai...

  20. A BRIEF HINDI REFERENCE GRAMMAR. PRELIMINARY VERSION.

    Science.gov (United States)

    GUMPERZ, JOHN J.; MISRA, VIDYA NIWAS

    THIS BRIEF OUTLINE OF HINDI PHONOLOGY AND GRAMMAR IS INTENDED FOR FIRST AND SECOND YEAR STUDENTS OF HINDI WHO HAVE SOME PREVIOUS KNOWLEDGE OF THE ORAL AND WRITTEN LANGUAGE BUT WHO MAY HAVE HAD NO PREVIOUS TRAINING IN LINGUISTIC TERMINOLOGY. THE AUTHORS HAVE THEREFORE EMPHASIZED SIMPLICITY AND READABILITY RATHER THAN EXHAUSTIVENESS OR ORIGINALITY…

  1. Math Placement: The Importance of Getting It Right for All Students. Research Brief

    Science.gov (United States)

    Fong, Anthony; Finkelstein, Neal

    2014-01-01

    Given the Common Core State Standards for Mathematics, California's history of math acceleration in the middle grades, and the concern for correct math course placement for all students, this brief examines patterns from the past to shed light on considerations for the future. The brief, written by WestEd's Tony Fong and Neal Finkelstein, presents…

  2. Proactive and Brief Smoking Cessation Intervention for Smokers at Outdoor Smoking "Hotspots" in Hong Kong.

    Science.gov (United States)

    Chan, Sophia Siu Chee; Cheung, Yee Tak Derek; Wan, Zoe; Wang, Man Ping; Lam, Tai-Hing

    2018-04-01

    Increased outdoor smoking is a common phenomenon after indoor smoking bans were in place. A series of observational studies were conducted to evaluate a novel, proactive, and brief smoking cessation intervention at outdoor smoking "hotspots," i.e., outdoor public areas where ashtrays were available and smokers clustered to smoke. The number of smokers at 26 selected hotspots were observed and counted for two consecutive days. Further observations of the smokers' characteristics and brief smoking cessation intervention were conducted at ten of the hotspots with the greatest number of smokers. Responses of the smokers to the brief intervention, including a leaflet and brief smoking cessation advice using AWAR protocol delivered by trained smoking cessation ambassadors, were assessed. A total of 24,034 smokers were observed within 464 h, which equals 51.8 smokers per hour. Of the 5070 pedestrians observed at the ten hotspots during the intervention sessions, 1228 (24.2 %) were smokers. In the 1228 smokers who were approached during our intervention sessions, about two thirds were willing to receive the self-help leaflet on smoking cessation whereas about half received the brief smoking cessation advice. Recruiting smokers and delivering brief smoking cessation interventions at smoking hotspots are feasible and likely effective to reach large numbers of smokers. Studies to evaluate the effectiveness of using this approach for smoking cessation are warranted.

  3. Examination of the Brief Fear of Negative Evaluation Scale-Version 2 and the Brief Fear of Negative Evaluation Scale-Straightforward Items Factor Structure in a Sample of U.S. College Students

    Science.gov (United States)

    Liu, Liu; Lowe, Patricia A.

    2016-01-01

    The current study examined the factor structure of the Brief Fear of Negative Evaluation-Straightforward Items (BFNE-S) and the Brief Fear of Negative Evaluation-Version 2 (BFNE-II) among 151 college students from the United States. Results indicated that the BFNE-S and the BFNE-II scores demonstrated excellent internal consistency reliability.…

  4. Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression

    International Nuclear Information System (INIS)

    Chang, C.-J.; Hsu, C.-C.; Yung, M.-C.; Chen, K.-Y.; Tzao Ching; Wu, W.-F.; Chou, H.-Y.; Lee, Y.-Y.; Lu, K.-H.; Chiou, S.-H.; Ma, H.-I

    2009-01-01

    CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133 + ) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133 - cells. To evaluate the role of SirT1 in GBM-CD133 + , we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133 + . Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133 + to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in the inhibition of tumor growth in nude mice transplanted with GBM-CD133 + . Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133 + mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.

  5. Impact of brief communication training among hospital social workers.

    Science.gov (United States)

    Bunting, Morgan; Cagle, John G

    2016-01-01

    Hospital social workers are often the fulcrum of communication between physicians, patients, and families especially when patients are facing life-threatening illness. This study aims to understand the impact of a brief training for hospital social workers. The training is designed to improve communication skills and self-efficacy, as well as lessen fears of death and dying. Repeated-measures tests were used to assess outcomes across three time points. Twenty-nine university-based hospital social workers participated. Results trended in the desired directions. Communication self-efficacy improved immediately following the training, and this was sustained 1 month following training completion. Although participants were relatively experienced, improvement was still demonstrated and maintained suggesting brief communication training is promising for hospital social workers across the career.

  6. Brief cognitive therapy for avoidant personality disorder.

    Science.gov (United States)

    Rees, Clare S; Pritchard, Rhian

    2015-03-01

    Avoidant personality disorder (APD) is associated with a high level of impairment in multiple areas of functioning. However, research on the treatment of APD is scarce, and there is an absence of empirically evaluated effective treatment approaches available. This study offers a preliminary investigation of the use of brief cognitive therapy to treat APD. Two individuals, both with a principal diagnosis of APD, but who also possessed a number of comorbidities, participated in 12 weekly sessions. A series of diagnostic symptom severity, global functioning, and self-report measures were completed at pretreatment, posttreatment and at 6-week follow-up. In addition, regular monitoring of each participant's strength of belief in 4 personally identified cognitions associated with APD was completed. Reductions in APD symptoms, associated negative affect, and increases to quality of life were observed for both participants at posttreatment and follow-up phases. Results suggest that brief cognitive therapy may be an effective treatment for APD and that further studies with larger samples are warranted. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  7. Relationships between the Kaufman Brief Intelligence Test and the Wechsler Adult Intelligence Scale-Third Edition.

    Science.gov (United States)

    Walters, Steven O; Weaver, Kenneth A

    2003-06-01

    The Kaufman Brief Intelligence Test detects learning problems of young students and is a screen for whether a more comprehensive test of intelligence is needed. A study to assess whether this test was valid as an adult intelligence test was conducted with 20 undergraduate psychology majors. The correlations between the Kaufman Brief Intelligence Test's Composite, Vocabulary, and Matrices test scores and their corresponding Wechsler Adult Intelligence Scale-Third Edition test scores, the Full Scale (r=.88), Verbal (r=.77), and Performance scores (r=.87), indicated very strong relationships. In addition, no significant differences were obtained between the Composite, Vocabulary, and Matrices means of the Kaufman Brief Intelligence Test and the Full Scale, Verbal, and Performance means of the WAIS-III. The Kaufman Brief Intelligence Test appears to be a valid test of intelligence for adults.

  8. A brief survey of atomic parity nonconservation experiments

    International Nuclear Information System (INIS)

    He Maoqi; Zhao Youyuan; Cai Shengshan; Zhang ZHiming

    1990-01-01

    The authors present a brief description of the basic idea of atomic parity nonconservation (PNC) effect, introduce the methods and results of measuring PNC, analyse the reasons to continue with atomic PNC experiments and suggest some ideas to improve the measure of PNC

  9. 14 CFR 91.1013 - Operational control briefing and acknowledgment.

    Science.gov (United States)

    2010-01-01

    ... Ownership Operations Operational Control § 91.1013 Operational control briefing and acknowledgment. (a) Upon...) Liability risk in the event of a flight-related occurrence that causes personal injury or property damage...

  10. Fluid intelligence: A brief history.

    Science.gov (United States)

    Kent, Phillip

    2017-01-01

    The concept of fluid and crystallized intelligence was introduced to the psychological community approximately 75 years ago by Raymond B. Cattell, and it continues to be an area of active research and controversy. The purpose of this paper is to provide a brief overview of the origin of the concept, early efforts to define intelligence and uses of intelligence tests to address pressing social issues, and the ongoing controversies associated with fluid intelligence and the structure of intelligence. The putative neuropsychological underpinnings and neurological substrates of fluid intelligence are discussed.

  11. MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.

    Science.gov (United States)

    Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A; Pfeffer, Lawrence M

    2017-12-22

    Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro , and inhibited GBM tumorigenesis in vivo . Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro , and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway.

  12. The novel Hsp90 inhibitor NXD30001 induces tumor regression in a genetically engineered mouse model of glioblastoma multiforme.

    Science.gov (United States)

    Zhu, Haihao; Woolfenden, Steve; Bronson, Roderick T; Jaffer, Zahara M; Barluenga, Sofia; Winssinger, Nicolas; Rubenstein, Allan E; Chen, Ruihong; Charest, Al

    2010-09-01

    Glioblastoma multiforme (GBM) has an abysmal prognosis. We now know that the epidermal growth factor receptor (EGFR) signaling pathway and the loss of function of the tumor suppressor genes p16Ink4a/p19ARF and PTEN play a crucial role in GBM pathogenesis: initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. We have recently shown that this genetic combination is sufficient to promote the development of GBM in adult mice. Therapeutic agents raised against single targets of the EGFR signaling pathway have proven rather inefficient in GBM therapy, showing the need for combinatorial therapeutic approaches. An effective strategy for concurrent disruption of multiple signaling pathways is via the inhibition of the molecular chaperone heat shock protein 90 (Hsp90). Hsp90 inhibition leads to the degradation of so-called client proteins, many of which are key effectors of GBM pathogenesis. NXD30001 is a novel second generation Hsp90 inhibitor that shows improved pharmacokinetic parameters. Here we show that NXD30001 is a potent inhibitor of GBM cell growth in vitro consistent with its capacity to inhibit several key targets and regulators of GBM biology. We also show the efficacy of NXD30001 in vivo in an EGFR-driven genetically engineered mouse model of GBM. Our findings establish that the Hsp90 inhibitor NXD30001 is a therapeutically multivalent molecule, whose actions strike GBM at the core of its drivers of tumorigenesis and represent a compelling rationale for its use in GBM treatment.

  13. Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma

    Science.gov (United States)

    Bagó, Juli R.; Pegna, Guillaume J.; Okolie, Onyi; Mohiti-Asli, Mahsa; Loboa, Elizabeth G.; Hingtgen, Shawn D.

    2017-01-01

    Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(l-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer. PMID:27016620

  14. Creating illusions of past encounter through brief exposure.

    Science.gov (United States)

    Brown, Alan S; Marsh, Elizabeth J

    2009-05-01

    Titchener (1928) suggested that briefly glancing at a scene could make it appear strangely familiar when it was fully processed moments later. The closest laboratory demonstration used words as stimuli, and showed that briefly glancing at a to-be-judged word increased the subject's belief that it had been presented in an earlier study list (Jacoby & Whitehouse, 1989). We evaluated whether a hasty glance could elicit a false belief in a prior encounter, from a time and place outside of the experiment. This goal precluded using word stimuli, so we had subjects evaluate unfamiliar symbols. Each symbol was preceded by a brief exposure to an identical symbol, a different symbol, or no symbol. A brief glance at an identical symbol increased attributions to preexperimental experience, relative to a glance at a different symbol or no symbol, providing a possible mechanism for common illusions of false recognition.

  15. MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo

    KAUST Repository

    Yang, Guang

    2014-01-23

    BackgroundRecent studies have revealed that miR-196a is upregulated in glioblastoma multiforme (GBM) and that it correlates with the clinical outcome of patients with GBM. However, its potential regulatory mechanisms in GBM have never been reported.MethodsWe used quantitative real-time PCR to assess miR-196a expression levels in 132 GBM specimens in a single institution. Oncogenic capability of miR-196a was detected by apoptosis and proliferation assays in U87MG and T98G cells. Immunohistochemistry was used to determine the expression of IκBα in GBM tissues, and a luciferase reporter assay was carried out to confirm whether IκBα is a direct target of miR-196a. In vivo, xenograft tumors were examined for an antiglioma effect of miR-196a inhibitors.ResultsWe present for the first time evidence that miR-196a could directly interact with IκBα 3′-UTR to suppress IκBα expression and subsequently promote activation of NF-κB, consequently promoting proliferation of and suppressing apoptosis in GBM cells both in vitro and in vivo. Our study confirmed that miR-196a was upregulated in GBM specimens and that high levels of miR-196a were significantly correlated with poor outcome in a large cohort of GBM patients. Our data from human tumor xenografts in nude mice treated with miR-196 inhibitors demonstrated that inhibition of miR-196a could ameliorate tumor growth in vivo.ConclusionsMiR-196a exerts its oncogenic effect in GBM by inhibiting IκBα both in vitro and in vivo. Our findings provide new insights into the pathogenesis of GBM and indicate that miR-196a may predict clinical outcome of GBM patients and serve as a new therapeutic target for GBM. © 2014 © The Author(s) 2014. 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. Connective tissue growth factor (CTGF/CCN2 is negatively regulated during neuron-glioblastoma interaction.

    Directory of Open Access Journals (Sweden)

    Luciana F Romão

    Full Text Available Connective-tissue growth factor (CTGF/CCN2 is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular matrix remodeling. Glioblastoma (GBM is the major malignant primary brain tumor and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGFβ luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out an interesting view in the understanding of the tumor and cerebral microenvironment

  17. Maryland and District of Columbia State Briefing Book for low-level radioactive waste management

    International Nuclear Information System (INIS)

    1981-09-01

    The District of Columbia and Maryland State Briefing Book is one of a series of state briefing books on low-level radioactive waste management practices. It has been prepared to assist state and federal agency officials in planning for safe low-level radioactive waste disposal. The report contains a profile of low-level radioactive waste generators in the District of Columbia and Maryland. The profile is the result of a survey of NRC licensees in the District of Columbia and Maryland. The briefing book also contains a comprehensive assessment of low-level radioactive waste management issues and concerns as defined by all major interested parties including industry, government, the media, and interest groups. The assessment was developed through personal communications with representatives of interested parties, and through a review of media sources. Lastly, the briefing book provides demographic and socioeconomic data and a discussion of relevant government agencies and activities, all of which may impact waste management practices in the District of Columbia and Maryland

  18. Genre Identification of Very Brief Musical Excerpts

    Science.gov (United States)

    Mace, Sandra T.; Wagoner, Cynthia L.; Teachout, David J.; Hodges, Donald A.

    2012-01-01

    The purpose of this study was to examine how well individuals were able to identify different music genres from very brief excerpts and whether musical training, gender and preference played a role in genre identification. Listeners were asked to identify genre from classical, jazz, country, metal, and rap/hip hop excerpts that were 125, 250, 500,…

  19. Trouble Brewing in Orange County. Policy Brief

    Science.gov (United States)

    Buck, Stuart

    2010-01-01

    Orange County will soon face enormous budgetary pressures from the growing deficits in public pensions, both at a state and local level. In this policy brief, the author estimates that Orange County faces a total $41.2 billion liability for retiree benefits that are underfunded--including $9.4 billion for the county pension system and an estimated…

  20. Trouble Brewing in San Francisco. Policy Brief

    Science.gov (United States)

    Buck, Stuart

    2010-01-01

    The city of San Francisco will face enormous budgetary pressures from the growing deficits in public pensions, both at a state and local level. In this policy brief, the author estimates that San Francisco faces an aggregate $22.4 billion liability for pensions and retiree health benefits that are underfunded--including $14.1 billion for the city…