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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. 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...

  3. 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...

  4. The Accuracy of GBM GRB Localizations

    Science.gov (United States)

    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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  11. 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.)

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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....

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  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. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  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. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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-.

  5. 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 ...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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}.

  2. 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/.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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 .

  4. 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.

  5. 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.

  6. 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 .

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  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. 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.

  17. 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.

  18. 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).

  19. 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…

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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. 

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.)

  20. 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.

  1. 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....

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  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. 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.

  4. 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…

  5. 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

  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. 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)

  8. 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...

  9. 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.

  10. 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)

  11. 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

  12. 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.

  13. 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...

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. 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

  7. A Brief Taxometrics Primer

    Science.gov (United States)

    Beauchaine, Theodore P.

    2009-01-01

    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 several taxometric procedures, (b) example analyses using simulated data, and (c) strategies for avoiding common pitfalls that are often observed in taxometrics research. To date, most taxometrics studies have appeared in the adult psychopathology literature. It is hoped that this primer will encourage interested readers to extend taxometrics research to child and adolescent populations. PMID:18088222

  8. 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

  9. 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…

  10. 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...

  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. 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.

  13. 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.

  14. Brief review: delirium

    Directory of Open Access Journals (Sweden)

    Schmitz ED

    2014-12-01

    Full Text Available No abstract available. Article truncated after 150 words. A significant number of patients develop a decline in cognitive function while hospitalized. Delirium in the intensive care increases mortality and healthcare costs and should be recognized and treated promptly (1,2. This is a brief review of delirium and important treatment options such as early percutaneous tracheostomy, neuroleptics, propofol, daily awakenings and reorientation by all team members. We recommend neither neuroimaging nor neurology consultation unless physical exam suggests an acute cerebral vascular accident or status epilepticus as the majority of these patients require no neurologic intervention and may be harmed by transportation to obtain additional testing. The DSM-5 defines delirium as a disturbance in attention (reduced ability to direct, focus, sustain, and shift attention and awareness (reduced orientation to the environment. The disturbance develops over a short period of time (usually hours to a few days, represents a change from baseline attention and awareness, and tends to fluctuate in severity ...

  15. 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).

  16. Neuroophthalmology A brief Vademecum

    International Nuclear Information System (INIS)

    Schwarz, Urs

    2004-01-01

    The stunning, intricate interaction between the visual, vestibular and optomotor systems--each a miracle on its own--ensures maintenance of orientation in space as well as visual recognition and target selection despite a host of sensory conflicts and adversary disturbances. Their main goals are to keep a target of interest on the fovea by either maintaining or shifting the direction of gaze in order to produce an accurate internal representation of the visual surroundings, in particular the selected target, and to continuously mirror the spatial relationship between these various visual elements and the self. Not surprising, the implementation of this host of elaborate neural networks encompasses almost every part of the brain, including the brainstem, cerebellum, extrapyramidal system and many areas of the cerebral cortex. Thus far, these systems are among the best investigated in brain research; and enormous knowledge was amassed over the last century employing a variety of techniques, including single cell recordings, eye movement studies, functional imaging and neuropsychological observations. In addition, this prolific line of research has enlightened many fundamental principles of neural and neuronal processing, which have subsequently enriched other fields of brain research as well as computational neuroscience, e.g. the discovery of receptive fields, which have now become a ubiquitous concept in many other areas of neurophysiology. This (improperly) brief, fractional and undoubtedly biased Vademecum is meant to accompany the reader into this marvellous field of neurophysiology and neurology. In particular, it stresses the clinical application of its functional neuroanatomy at the bedside, which, in many respects, is superior to other means of investigating a patient

  17. Neuroophthalmology A brief Vademecum

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Urs E-mail: us@neurol.unizh.ch

    2004-01-01

    The stunning, intricate interaction between the visual, vestibular and optomotor systems--each a miracle on its own--ensures maintenance of orientation in space as well as visual recognition and target selection despite a host of sensory conflicts and adversary disturbances. Their main goals are to keep a target of interest on the fovea by either maintaining or shifting the direction of gaze in order to produce an accurate internal representation of the visual surroundings, in particular the selected target, and to continuously mirror the spatial relationship between these various visual elements and the self. Not surprising, the implementation of this host of elaborate neural networks encompasses almost every part of the brain, including the brainstem, cerebellum, extrapyramidal system and many areas of the cerebral cortex. Thus far, these systems are among the best investigated in brain research; and enormous knowledge was amassed over the last century employing a variety of techniques, including single cell recordings, eye movement studies, functional imaging and neuropsychological observations. In addition, this prolific line of research has enlightened many fundamental principles of neural and neuronal processing, which have subsequently enriched other fields of brain research as well as computational neuroscience, e.g. the discovery of receptive fields, which have now become a ubiquitous concept in many other areas of neurophysiology. This (improperly) brief, fractional and undoubtedly biased Vademecum is meant to accompany the reader into this marvellous field of neurophysiology and neurology. In particular, it stresses the clinical application of its functional neuroanatomy at the bedside, which, in many respects, is superior to other means of investigating a patient.

  18. 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.

  19. Assessing the role of STAT3 in DC differentiation and autologous DC immunotherapy in mouse models of GBM.

    Directory of Open Access Journals (Sweden)

    Hikmat Assi

    Full Text Available Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.

  20. Assessing the role of STAT3 in DC differentiation and autologous DC immunotherapy in mouse models of GBM.

    Science.gov (United States)

    Assi, Hikmat; Espinosa, Jaclyn; Suprise, Sarah; Sofroniew, Michael; Doherty, Robert; Zamler, Daniel; Lowenstein, Pedro R; Castro, Maria G

    2014-01-01

    Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.

  1. 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

  2. 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

  3. 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

  4. Electricity Storage. Technology Brief

    Energy Technology Data Exchange (ETDEWEB)

    Simbolotti, G. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development ENEA, Rome (Italy); Kempener, R. [International Renewable Energy Agency IRENA, Bonn (Germany)

    2012-04-15

    Electricity storage is a key technology for electricity systems with a high share of renewables as it allows electricity to be generated when renewable sources (i.e. wind, sunlight) are available and to be consumed on demand. It is expected that the increasing price of fossil fuels and peak-load electricity and the growing share of renewables will result in electricity storage to grow rapidly and become more cost effective. However, electricity storage is technically challenging because electricity can only be stored after conversion into other forms of energy, and this involves expensive equipment and energy losses. At present, the only commercial storage option is pumped hydro power where surplus electricity (e.g. electricity produced overnight by base-load coal or nuclear power) is used to pump water from a lower to an upper reservoir. The stored energy is then used to produce hydropower during daily high-demand periods. Pumped hydro plants are large-scale storage systems with a typical efficiency between 70% and 80%, which means that a quarter of the energy is lost in the process. Other storage technologies with different characteristics (i.e. storage process and capacity, conversion back to electricity and response to power demand, energy losses and costs) are currently in demonstration or pre-commercial stages and discussed in this brief report: Compressed air energy storage (CAES) systems, Flywheels; Electrical batteries; Supercapacitors; Superconducting magnetic storage; and Thermal energy storage. No single electricity storage technology scores high in all dimensions. The technology of choice often depends on the size of the system, the specific service, the electricity sources and the marginal cost of peak electricity. Pumped hydro currently accounts for 95% of the global storage capacity and still offers a considerable expansion potential but does not suit residential or small-size applications. CAES expansion is limited due to the lack of suitable

  5. 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.

  6. 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

  7. Fermi GBM Trigger Catalog

    Data.gov (United States)

    National Aeronautics and Space Administration — Fermi is a powerful space observatory that will open a wide window on the universe. Gamma rays are the highest-energy form of light, and the gamma-ray sky is...

  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. 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.

  10. 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)

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Science.gov (United States)

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  16. Intravitreal Bevacizumab (Avastin for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Directory of Open Access Journals (Sweden)

    J. Fernando Arevalo

    2011-01-01

    Full Text Available This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB on diabetic retinopathy (DR including diabetic macular edema (DME and proliferative diabetic retinopathy (PDR at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD, and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

  17. 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.

  18. 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.

  19. 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/.

  20. A brief history of videogames

    Directory of Open Access Journals (Sweden)

    Simone Belli

    2008-11-01

    Full Text Available The following text contains a brief journey through a short and yet intense adventure, the history of videogames. Since its beginnings in the 1950's decade to the present time, videogames have progressively changed from a hobby for ingeneering studens to the most powerfull leisure industry. In order to gain a better understanding of this phenomenon it is necessary to look over the path of its transformation from a retrospecive point of view. Such a look has necessarily to focus on those devices and games that had made a landmark in the history of videogames, taking them to their current position. Besides, it is crucial to address their implications in contemporary visual culture, along with current prejudices against them. This is a short account about a great history.

  1. Breast Abscess: A Brief Communication

    Directory of Open Access Journals (Sweden)

    Pradipta Das

    2017-07-01

    Full Text Available Breast infections commonly affect women aged between 18 and 50 years and are categorized as lactational and non-lactational infections. The infection can affect the skin overlying the breast when it can be a primary event or, it may occur secondary to mastitis and/or, secondary to a lesion in the skin. The commoner clinical findings consist of a tender, hard breast mass with erythema of the overlying skin. Needle aspiration yields pus cultures of which yield the infecting microorganisms. In practice, treatment is usually empiric consisting of bed rest, frequent nursing, fluids, Acetaminophen for pain and fever and a course of antibiotics. The other common line of treatment for breast abscess consists of incision and drainage with primary and/or, secondary closure. This brief communication on breast abscess gives an overview of the possible etiologies, clinical signs and symptoms and the treatment lines for breast abscess.

  2. A brief introduction to probability.

    Science.gov (United States)

    Di Paola, Gioacchino; Bertani, Alessandro; De Monte, Lavinia; Tuzzolino, Fabio

    2018-02-01

    The theory of probability has been debated for centuries: back in 1600, French mathematics used the rules of probability to place and win bets. Subsequently, the knowledge of probability has significantly evolved and is now an essential tool for statistics. In this paper, the basic theoretical principles of probability will be reviewed, with the aim of facilitating the comprehension of statistical inference. After a brief general introduction on probability, we will review the concept of the "probability distribution" that is a function providing the probabilities of occurrence of different possible outcomes of a categorical or continuous variable. Specific attention will be focused on normal distribution that is the most relevant distribution applied to statistical analysis.

  3. 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

  4. 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...

  5. 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...

  6. 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.

  7. 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.

  8. Engineering Technical Review Planning Briefing

    Science.gov (United States)

    Gardner, Terrie

    2012-01-01

    The general topics covered in the engineering technical planning briefing are 1) overviews of NASA, Marshall Space Flight Center (MSFC), and Engineering, 2) the NASA Systems Engineering(SE) Engine and its implementation , 3) the NASA Project Life Cycle, 4) MSFC Technical Management Branch Services in relation to the SE Engine and the Project Life Cycle , 5) Technical Reviews, 6) NASA Human Factor Design Guidance , and 7) the MSFC Human Factors Team. The engineering technical review portion of the presentation is the primary focus of the overall presentation and will address the definition of a design review, execution guidance, the essential stages of a technical review, and the overall review planning life cycle. Examples of a technical review plan content, review approaches, review schedules, and the review process will be provided and discussed. The human factors portion of the presentation will focus on the NASA guidance for human factors. Human factors definition, categories, design guidance, and human factor specialist roles will be addressed. In addition, the NASA Systems Engineering Engine description, definition, and application will be reviewed as background leading into the NASA Project Life Cycle Overview and technical review planning discussion.

  9. A brief history of CERN

    International Nuclear Information System (INIS)

    Jacob, M.

    2004-01-01

    This article draws a brief history of CERN that has just celebrated its jubilee. Today 20 member states contribute to its annual budget that reached 650 million euros in 2004. In 1954 CERN was created by 12 founder states for mainly 3 reasons: 1) to achieve a research facility dedicated to particle physics able to compete with its American counterparts and that no European country could afford alone, 2) to generate with scientific research an example and a promoter for future international collaborations, and 3) to make scientists from different countries that were at war a few years before, to work together. The creation of CERN has not led to a decline of national laboratories as it was feared in the fifties. On the contrary scientific and technical tasks have been dispatched: CERN provides member states with accelerator facilities while national laboratories and universities contribute to the design and fabrication of detectors and to the analysis of experimental data. The history of CERN is marked by 2 main scientific milestones, first the discovery of weak interaction through neutral currents in 1973 and secondly the discovery of W and Z bosons in 1983. (A.C.)

  10. NASA Tech Briefs, February 2009

    Science.gov (United States)

    2009-01-01

    Tech Briefs are short announcements of innovations originating from research and development activities of the National Aeronautics and Space Administration. They emphasize information considered likely to be transferable across industrial, regional, or disciplinary lines and are issued to encourage commercial application. Topics covered include: Measuring Low Concentrations of Liquid Water in Soil; The Mars Science Laboratory Touchdown Test Facility; Non-Contact Measurement of Density and Thickness Variation in Dielectric Materials; Compact Microwave Fourier Spectrum Analyzer; InP Heterojunction Bipolar Transistor Amplifiers to 255 GHz; Combinatorial Generation of Test Suites; In-Phase Power-Combined Frequency Tripler at 300 GHz; Electronic System for Preventing Airport Runway Incursions; Smaller but Fully Functional Backshell for Cable Connector; Glove-Box or Desktop Virtual-Reality System; Composite Layer Manufacturing with Fewer Interruptions; Improved Photoresist Coating for Making CNT Field Emitters; A Simplified Diagnostic Method for Elastomer Bond Durability; Complex Multifunctional Polymer/Carbon-Nanotube Composites; Very High Output Thermoelectric Devices Based on ITO Nanocomposites; Reducing Unsteady Loads on a Piggyback Miniature Submarine; Ultrasonic/Sonic Anchor; Grooved Fuel Rings for Nuclear Thermal Rocket Engines; Pulsed Operation of an Ion Accelerator; Autonomous Instrument Placement for Mars Exploration Rovers; Mission and Assets Database; TCP/IP Interface for the Satellite Orbit Analysis Program (SOAP); Trajectory Calculator for Finite-Radius Cutter on a Lathe; Integrated System Health Management Development Toolkit.

  11. A Brief History of Shigella.

    Science.gov (United States)

    Lampel, Keith A; Formal, Samuel B; Maurelli, Anthony T

    2018-01-01

    The history of Shigella , the causative agent of bacillary dysentery, is a long and fascinating one. This brief historical account starts with descriptions of the disease and its impact on human health from ancient time to the present. Our story of the bacterium starts just before the identification of the dysentery bacillus by Kiyoshi Shiga in 1898 and follows the scientific discoveries and principal scientists who contributed to the elucidation of Shigella pathogenesis in the first 100 years. Over the past century, Shigella has proved to be an outstanding model of an invasive bacterial pathogen and has served as a paradigm for the study of other bacterial pathogens. In addition to invasion of epithelial cells, some of those shared virulence traits include toxin production, multiple-antibiotic resistance, virulence genes encoded on plasmids and bacteriophages, global regulation of virulence genes, pathogenicity islands, intracellular motility, remodeling of host cytoskeleton, inflammation/polymorphonuclear leukocyte signaling, apoptosis induction/inhibition, and "black holes" and antivirulence genes. While there is still much to learn from studying Shigella pathogenesis, what we have learned so far has also contributed greatly to our broader understanding of bacterial pathogenesis.

  12. Brief review of neutrino physics

    International Nuclear Information System (INIS)

    Sciulli, F.

    1986-01-01

    This paper provides a brief review of neutrino physics. The running of the coupling constant, α/sub s/, predicted by QCD is not seen presently by using measurements of R/sub hadron/. However, the systematic errors on the measurements still allow a running α/sub s/. It should be noted that when calculating α/sub s/ at the J/psi and Υ using the technique of a previous work, a running α/sub s/ is also not observed, but is allowed within error. Evidence for the three gluon coupling predicted by QCD is still lacking. The search for gluonic mesons has continued to be inconclusive, even though candidate meson properties have been considerably refined. Searches for right-handed currents have so far proved negative, though impressive mass limits have been obtained. Searches for supersymmetric particles have also proved negative, with mass limits strongly coupled to accelerator energy. Much enthusiasm and inventiveness has been generated by the announcement of two possible new states, ξ and zeta however, the existence of these states is presently uncertain. In the case of the zeta, theoretical interpretation outside the S-M played a very prominent role

  13. Brief concept of hip preservation

    Directory of Open Access Journals (Sweden)

    Sanjeev S. Madan

    2017-12-01

    Full Text Available Restoration of the anatomy of the hip joint and biomechanics across it, carry the immense importance to prevent future osteoarthritis of the joint. The aim of this review is to provide the brief concept of the methods to preserve the hip, especially in young adults. Attempts to preserve the hips start with the intense preoperative planning of the corrective procedure. Different parameters regarding the femur and acetabulum in all 3 dimensions need to be assessed. Especially, measurement of the anteversion of the femur and acetabulum is a significant step to avoid osteoarthritis. In addition, the suprapelvic and infrapelvic (spine and lower limb lengths alignment needs to be considered in the planning. Correction of the femoral side of the hip needs the understanding of the blood supply of the proximal femur which carries the risk of avascular necrosis more so with intracapsular osteotomies. Acetabular reorientation, to re-distribute the forces over the weight bearing part, can be carried out with re-directional osteotomy such as periacetabular osteotomy. It needs the understanding of the acetabular anatomy and the force distribution in it. To conclude, correction of both femoral and acetabular side parameters need to be considered in decision making depending on the alterations due to various etiologies causing the hip disorders.

  14. 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.

  15. NASA Tech Briefs, January 2009

    Science.gov (United States)

    2009-01-01

    Tech Briefs are short announcements of innovations originating from research and development activities of the National Aeronautics and Space Administration. They emphasize information considered likely to be transferable across industrial, regional, or disciplinary lines and are issued to encourage commercial application. Topics covered include: The Radio Frequency Health Node Wireless Sensor System; Effects of Temperature on Polymer/Carbon Chemical Sensors; Small CO2 Sensors Operate at Lower Temperature; Tele-Supervised Adaptive Ocean Sensor Fleet; Synthesis of Submillimeter Radiation for Spectroscopy; 100-GHz Phase Switch/Mixer Containing a Slot-Line Transition; Generating Ka-Band Signals Using an X-Band Vector Modulator; SiC Optically Modulated Field-Effect Transistor; Submillimeter-Wave Amplifier Module with Integrated Waveguide Transitions; Metrology System for a Large, Somewhat Flexible Telescope; Economical Implementation of a Filter Engine in an FPGA; Improved Joining of Metal Components to Composite Structures; Machined Titanium Heat-Pipe Wick Structure; Gadolinia-Doped Ceria Cathodes for Electrolysis of CO2; Utilizing Ocean Thermal Energy in a Submarine Robot; Fuel-Cell Power Systems Incorporating Mg-Based H2 Generators; Alternative OTEC Scheme for a Submarine Robot; Sensitive, Rapid Detection of Bacterial Spores; Adenosine Monophosphate-Based Detection of Bacterial Spores; Silicon Microleaks for Inlets of Mass Spectrometers; CGH Figure Testing of Aspherical Mirrors in Cold Vacuums; Series-Coupled Pairs of Silica Microresonators; Precise Stabilization of the Optical Frequency of WGMRs; Formation Flying of Components of a Large Space Telescope; Laser Metrology Heterodyne Phase-Locked Loop; Spatial Modulation Improves Performance in CTIS; High-Performance Algorithm for Solving the Diagnosis Problem; Truncation Depth Rule-of-Thumb for Convolutional Codes; Efficient Method for Optimizing Placement of Sensors.

  16. 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.

  17. 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.

  18. 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

  19. Impacts of climate change and socio-economic scenarios on flow and water quality of the Ganges, Brahmaputra and Meghna (GBM) river systems: low flow and flood statistics.

    Science.gov (United States)

    Whitehead, P G; Barbour, E; Futter, M N; Sarkar, S; Rodda, H; Caesar, J; Butterfield, D; Jin, L; Sinha, R; Nicholls, R; Salehin, M

    2015-06-01

    The potential impacts of climate change and socio-economic change on flow and water quality in rivers worldwide is a key area of interest. The Ganges-Brahmaputra-Meghna (GBM) is one of the largest river basins in the world serving a population of over 650 million, and is of vital concern to India and Bangladesh as it provides fresh water for people, agriculture, industry, conservation and for the delta system downstream. This paper seeks to assess future changes in flow and water quality utilising a modelling approach as a means of assessment in a very complex system. The INCA-N model has been applied to the Ganges, Brahmaputra and Meghna river systems to simulate flow and water quality along the rivers under a range of future climate conditions. Three model realisations of the Met Office Hadley Centre global and regional climate models were selected from 17 perturbed model runs to evaluate a range of potential futures in climate. In addition, the models have also been evaluated using socio-economic scenarios, comprising (1) a business as usual future, (2) a more sustainable future, and (3) a less sustainable future. Model results for the 2050s and the 2090s indicate a significant increase in monsoon flows under the future climates, with enhanced flood potential. Low flows are predicted to fall with extended drought periods, which could have impacts on water and sediment supply, irrigated agriculture and saline intrusion. In contrast, the socio-economic changes had relatively little impact on flows, except under the low flow regimes where increased irrigation could further reduce water availability. However, should large scale water transfers upstream of Bangladesh be constructed, these have the potential to reduce flows and divert water away from the delta region depending on the volume and timing of the transfers. This could have significant implications for the delta in terms of saline intrusion, water supply, agriculture and maintaining crucial ecosystems such

  20. IT-26IDENTIFICATION OF PSEUDO-PROGRESSION IN NEW DIAGNOSED GLIOBLASTOMA (GBM) IN A RANDOMIZED PHASE 2 OF ICT-107: MRI AND PATHOLOGY CORRELATION

    Science.gov (United States)

    Phuphanich, Surasak; Yu, John; Bannykh, Serguei; Zhu, Jay-Jiguang

    2014-01-01

    BACKGROUND: Previously reports of pseudo-progression in patients with brain tumor after therapeutic vaccines in pediatric and adult glioma (Pollack, JCO online on June 2, 2014 and Okada, JCO Jan 20, 2011; 29: 330-336) demonstrated that RANO criteria for tumor progression may not be adequate for immunotherapy trials. Similar observations were also seen in other checkpoint inhibitor in melanoma and NSLSC. METHODS: We identified 2 patients, who developed tumor progression by RANO criteria, underwent surgery following enrollment in a phase 2 randomized ICT-107 (an autologous vaccine consisting of patient dendritic cells pulsed with peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, MAGE1) after radiation and Temozolomide (TMZ). RESULTS: The first case is a 69 years old Chinese male, who underwent 1st surgery of gross total resection right occipital GBM on 10/26/2011. Subsequently he received 19 cycles of TMZ and 9 vaccines/placebo. MRI from 7/2/2013 showed enhancement surrounding surgical cavity. After 2nd surgery, pathology showed only rare residual tumor cells with macrophages and positive CD 8 cells. He continued on this vaccine program and MRI showed more progression with finger-like extension into parietal lobe 4 months later. The 3rd surgery also showed extensive reactive changes with no active tumor cells. For 2nd case, a 62 years old male, who underwent first surgery on 7/11/2011 of right temporal lobe, developed 2 areas of enhancement after 6 cycles of TMZ and 7 vaccines/placebo on 4/18/2012. With 2nd surgery, pathology showed reactive gliosis without active tumor. The subject continued in this trial. CONCLUSION: Pseudo-progression was confirmed by pathology in these 2 patients at 20 and 9 months which were delayed comparing to pseudo-progression observed in patients treated with concurrent XRT/TMZ (3-6 months). Future iRANO criteria development is essential for immunotherapy trials. Accurately identifying and managing such patients is necessary to avoid

  1. 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.

  2. 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.

  3. 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 ...

  4. 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.)

  5. 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…

  6. 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.

  7. 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…

  8. 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)…

  9. 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

  10. 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.

  11. 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…

  12. 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,…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. Trouble Brewing in Los Angeles. Policy Brief

    Science.gov (United States)

    Buck, Stuart

    2010-01-01

    The city of Los Angeles 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 Los Angeles faces a total $152.6 billion liability for pensions that are underfunded--including $49.1 billion for the city pension systems, $2.4 billion for…

  18. 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.

  19. 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)

  20. 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.

  1. 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…

  2. 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…

  3. 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.

  4. 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....

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. Briefing paper for universities on Core Maths

    OpenAIRE

    Glaister, Paul

    2015-01-01

    This briefing paper outlines the rationale for and development of the new Core Maths qualifications, the characteristics of Core Maths, and why Core Maths is important for higher education. It is part of a communication to university vice-chancellors from the Department for Business, Innovation and Skills (BIS) comprising this paper and a joint Ministerial letter from Jo Johnson, Minister of State for Universities and Science in BIS, and Nick Gibb, Minister of State for Schools in the Departm...

  10. MENA Quarterly Economic Brief, July 2015

    OpenAIRE

    Devarajan, Shanta; Mottaghi, Lili

    2015-01-01

    Iran and the Permanent Members of the UN Security Council and Germany (P5+1) reached a deal on July 14, 2015 that limits Iranian nuclear activity in return for lifting all international sanctions that were placed on Iran (Box 1). This issue of the MENA Quarterly Economic Brief (QEB) traces the economic effects of this development—removing sanctions on Iran—on the world oil market, on Iran’s trading partners, and on the Iranian economy.

  11. Urban Assault Vehicle: Some Ideas (Briefing Charts)

    Science.gov (United States)

    2013-11-25

    Brief 2 Dismount Support ( Exoskeleton , robots , personal mobility) • Power • Information/ networking • Movement • Resupply • Tactical... Benefit – able to transition to support a 3d battlefield (urban) • Dispersion when it makes sense 16 from or UNCLASSIFIED Exoskeleton Based...to spark thought and not be comprehensive. UNCLASSIFIED Exoskeletons : How to Support? 3 Sarcos XOS 2 suit- 25x strength amplification, but

  12. Trouble Brewing in San Diego. Policy Brief

    Science.gov (United States)

    Buck, Stuart

    2010-01-01

    The city of San Diego 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 Diego faces total of $45.4 billion, including $7.95 billion for the county pension system, $5.4 billion for the city pension system, and an estimated $30.7…

  13. Interviewing: Methodological Briefs - Impact Evaluation No. 12

    OpenAIRE

    Bronwen McDonald; Patricia Rogers

    2014-01-01

    Interviews are easy to do badly and hard to do well - good planning, adequate time and appropriate skills are required. The type of interview should be carefully chosen to suit the situation rather than choosing a type of interview (such as focus groups) simply because it is commonly used. Interviews with children raise particular ethical issues that need to be carefully considered and fully addressed. This brief outlines key issues to consider in planning interviews for impact evaluation, ta...

  14. The Brief Negative Symptom Scale: Psychometric Properties

    OpenAIRE

    Kirkpatrick, Brian; Strauss, Gregory P.; Nguyen, Linh; Fischer, Bernard A.; Daniel, David G.; Cienfuegos, Angel; Marder, Stephen R.

    2010-01-01

    The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test–retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93...

  15. Reincarnation in America: A Brief Historical Overview

    OpenAIRE

    Lee Irwin

    2017-01-01

    American theories of reincarnation have a long and complex history, dating from 1680s to the present. It is the purpose of this paper to highlight the main currents of reincarnation theory in the American context, giving a brief historical survey. Sources surveyed begin with Native American traditions, and then move to immigrant traditions based in Western Esotericism, Christianity, Judaism, missionary Hinduism and Buddhism, Spiritualism, Theosophy, Rosicrucianism, and concludes with more cur...

  16. Energy in Croatia 2008, Brief Report

    International Nuclear Information System (INIS)

    2009-01-01

    The sixth edition of concise energy review 'Energy in Croatia 2008' presents brief information on relations and developments in the Croatian energy sector to domestic and international audience. Apart od basic energy indicators, this report provides data on energy production and consumption, as well as energy commodities, balances for the past period. In addition, the report gives other interesting indicators, such as, basic facts on the Republic of Croatia, air pollutant emissions, energy prices, energy capacities and energy reserves. The report presents the croatian energy sector in practical and informative style

  17. Legal briefing: home birth and midwifery.

    Science.gov (United States)

    Pope, Thaddeus Mason; Fisch, Deborah

    2013-01-01

    This issue's "Legal Briefing" column covers recent legal developments involving home birth and midwifery in the United States. Specifically, we focus on new legislative, regulatory, and judicial acts that impact women's' access to direct entry (non-nurse) midwives. We categorize these legal developments into the following 12 categories. 1. Background and History 2. Certified Nurse-Midwives 3. Direct Entry Midwives 4. Prohibition of Direct Entry Midwives 5. Enforcement of Prohibition 6. Challenges to Prohibition 7. Forbearance without License 8. Voluntary Licensure 9. Unclear and Uncertain Status 10. Growth of DEM Licensure 11. Licensure Restrictions 12. Medicaid Coverage

  18. Frailty in elderly: a brief review.

    Science.gov (United States)

    Tabue-Teguo, Maturin; Simo, Nadine; Gonzalez-Colaço Harmand, Magali; Cesari, Matteo; Avila-Funes, Jose-Alberto; Féart, Catherine; Amiéva, Hélène; Dartigues, Jean-François

    2017-06-01

    The identification of frail older persons is a public health priority. Frailty is defined as an extreme vulnerability of the organism to endogenous and exogenous stressors, a syndrome that exposes the individual at higher risk of negative health-related outcomes as well as a transition phase between successful aging and disability. The theoretical concept of frailty is largely agreed, its practical translation still presents some limitations due to the existence of multiple tools and operational definition. In this brief review, we would like to clarify the frailty concept regarding scientific literature.

  19. Brief history of electronic stereoscopic displays

    Science.gov (United States)

    Lipton, Lenny

    2012-02-01

    A brief history of recent developments in electronic stereoscopic displays is given concentrating on products that have succeeded in the market place and hence have had a significant influence on future implementations. The concentration is on plano-stereoscopic (two-view) technology because it is now the dominant display modality in the marketplace. Stereoscopic displays were created for the motion picture industry a century ago, and this technology influenced the development of products for science and industry, which in turn influenced product development for entertainment.

  20. The brief negative symptom scale: psychometric properties.

    Science.gov (United States)

    Kirkpatrick, Brian; Strauss, Gregory P; Nguyen, Linh; Fischer, Bernard A; Daniel, David G; Cienfuegos, Angel; Marder, Stephen R

    2011-03-01

    The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test-retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93 for the BNSS total score and values of 0.89-0.95 for individual subscales. Comparisons with positive symptoms and other negative symptom instruments supported the discriminant and concurrent validity of the instrument.

  1. 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).

  2. 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)

  3. AJ26 rocket engine testing news briefing

    Science.gov (United States)

    2010-01-01

    NASA's John C. Stennis Space Center Director Gene Goldman (center) stands in front of a 'pathfinder' rocket engine with Orbital Sciences Corp. President and Chief Operating Officer J.R. Thompson (left) and Aerojet President Scott Seymour during a Feb. 24 news briefing at the south Mississippi facility. The leaders appeared together to announce a partnership for testing Aerojet AJ26 rocket engines at Stennis. The engines will be used to power Orbital's Taurus II space vehicles to provide commercial cargo transportation missions to the International Space Station for NASA. During the event, the Stennis partnership with Orbital was cited as an example of the new direction of NASA to work with commercial interests for space travel and transport.

  4. Briefing paper -- Remedial Action Assessment System

    International Nuclear Information System (INIS)

    Buelt, J.L.

    1990-04-01

    Congress has mandated a more comprehensive management of hazardous wastes with the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or ''Superfund'') and the Superfund Amendment and Reauthorization Act (SARA). This mandate includes restoration of disposal sites contaminated through past disposal practices. This mandate applies to facilities operated for and by the Department of Energy (DOE), just as it does to industrial and other institutions. To help implement the CERCLA/SARA remedial investigation and feasibility study (RI/FS) process in a consistent, timely, and cost-effective manner, a methodology needs to be developed that will allow definition, sorting, and screening of remediation technologies for each operable unit (waste site). This need is stated specifically in Section 2.2.2.1 of the October 1989 Applied Research, Development, Demonstration, Testing, and Evaluation (RDDT ampersand E) Plan of the DOE. This Briefing Paper is prepared to respond to this need. 1 fig

  5. Delusional disorders in dermatology: a brief review.

    Science.gov (United States)

    Robles, David T; Romm, Sharon; Combs, Heidi; Olson, Jonathan; Kirby, Phil

    2008-06-15

    There are several unique psychiatric disorders that are likely to present to a dermatologist because of their accompanying skin complaints. Delusions of parasitosis (DP) is a fixed, false belief of parasitic infestation that may lead patients to compulsively self-mutilate while attempting to remove the non-existent parasites. Morgellons disease is a controversial condition characterized by a fixed belief that fibers that are imbedded or extruding from the skin; this condition is likely in the spectrum of DP. Body dysmorphic disorder (BDD) is a preoccupation with an imagined defect in appearance that causes significant distress and is associated with time consuming rituals, isolation, depression, and increased risk of suicide. Olfactory reference syndrome (ORS) is a preoccupation with body odor leading to the stigmata of shame, embarrassment, and social isolation. This brief review examines each of these conditions and their management because any one of them may present to a dermatologist.

  6. Legal Briefing: Unwanted Cesareans and Obstetric Violence.

    Science.gov (United States)

    Pope, Thaddeus Mason

    2017-01-01

    A capacitated pregnant woman has a nearly unqualified right to refuse a cesarean section. Her right to say "no" takes precedence over clinicians' preferences and even over clinicians' concerns about fetal health. Leading medical societies, human rights organizations, and appellate courts have all endorsed this principle. Nevertheless, clinicians continue to limit reproductive liberty by forcing and coercing women to have unwanted cesareans. This "Legal Briefing" reviews recent court cases involving this type of obstetric violence. I have organized these court cases into the following six categories: 1. Epidemic of Unwanted Cesareans 2. Court-Ordered Cesareans 3. Physician-Coerced Cesareans 4. Physician-Ordered Cesareans 5. Cesareans for Incapacitated Patients 6. Cesareans for Patients in a Vegetative State or Who Are Brain Dead. Copyright 2017 The Journal of Clinical Ethics. All rights reserved.

  7. History of Hanford Site Defense Production (Brief)

    International Nuclear Information System (INIS)

    GERBER, M.S.

    2001-01-01

    This paper acquaints the audience with the history of the Hanford Site, America's first full-scale defense plutonium production site. The paper includes the founding and basic operating history of the Hanford Site, including World War II construction and operations, three major postwar expansions (1947-55), the peak years of production (1956-63), production phase downs (1964-the present), a brief production spurt from 1984-86, the end of the Cold War, and the beginning of the waste cleanup mission. The paper also delineates historical waste practices and policies as they changed over the years at the Hanford Site, past efforts to chemically treat, ''fractionate,'' and/or immobilize Hanford's wastes, and resulting major waste legacies that remain today. This paper presents original, primary-source research into the waste history of the Hanford Site. Finally, the paper places the current Hanford Site waste remediation endeavors in the broad context of American and world history

  8. Affordances for robots: a brief survey

    Directory of Open Access Journals (Sweden)

    Thomas E. Horton

    2012-12-01

    Full Text Available In this paper, we consider the influence of Gibson's affordance theory on the design of robotic agents. Affordance theory (and the ecological approach to agent design in general has in many cases contributed to the development of successful robotic systems; we provide a brief survey of AI research in this area. However, there remain significant issues that complicate discussions on this topic, particularly in the exchange of ideas between researchers in artificial intelligence and ecological psychology. We identify some of these issues, specifically the lack of a generally accepted definition of "affordance" and fundamental differences in the current approaches taken in AI and ecological psychology. While we consider reconciliation between these fields to be possible and mutually beneficial, it will require some flexibility on the issue of direct perception.

  9. A brief history of mechanical engineering

    CERN Document Server

    Dixit, Uday Shanker; Davim, J Paulo

    2017-01-01

    What is mechanical engineering? What a mechanical engineering does? How did the mechanical engineering change through ages? What is the future of mechanical engineering? This book answers these questions in a lucid manner. It also provides a brief chronological history of landmark events and answers questions such as: When was steam engine invented? Where was first CNC machine developed? When did the era of additive manufacturing start? When did the marriage of mechanical and electronics give birth to discipline of mechatronics? This book informs and create interest on mechanical engineering in the general public and particular in students. It also helps to sensitize the engineering fraternity about the historical aspects of engineering. At the same time, it provides a common sense knowledge of mechanical engineering in a handy manner.

  10. Brief wakeful resting can eliminate directed forgetting.

    Science.gov (United States)

    Schlichting, Andreas; Bäuml, Karl-Heinz T

    2017-02-01

    When cued to intentionally forget previously encoded memories, participants typically show reduced recall of the memories on a later recall test. We examined how such directed forgetting is affected by a brief period of wakeful resting between encoding and test. Encoding was followed by a "passive" wakeful resting period in which subjects heard emotionally neutral music or perceived neutral pictures, or it was followed by an "active" distraction period in which subjects were engaged in counting or calculation tasks. Whereas typical directed forgetting was present after active distraction, the forgetting was absent after wakeful resting. The findings indicate that the degree to which people can intentionally forget memories is influenced by the cognitive activity that people engage in shortly after learning takes place. The results provide first evidence on the interplay between wakeful resting and intentional forgetting.

  11. Reincarnation in America: A Brief Historical Overview

    Directory of Open Access Journals (Sweden)

    Lee Irwin

    2017-10-01

    Full Text Available American theories of reincarnation have a long and complex history, dating from 1680s to the present. It is the purpose of this paper to highlight the main currents of reincarnation theory in the American context, giving a brief historical survey. Sources surveyed begin with Native American traditions, and then move to immigrant traditions based in Western Esotericism, Christianity, Judaism, missionary Hinduism and Buddhism, Spiritualism, Theosophy, Rosicrucianism, and concludes with more current theoretical influences, based in paranormal science research. The paper demonstrates that current theories of reincarnation are increasingly less dependent upon religious support and increasingly based in direct personal experience, paranormal research, and new therapeutic models. The paper concludes with some reflections on the complexity of reincarnation theory and raises questions concerning the future development of such theory.

  12. A brief review on anterior urethral strictures

    Directory of Open Access Journals (Sweden)

    Li Cheng

    2018-04-01

    Full Text Available The treatment of urethral strictures remains a challenging field in urology even though there are a variety of procedures to treat it at present, as no one approach is superior over another. This paper reviewed the surgical options for the management of different sites and types of anterior urethral stricture, providing a brief discussion of the controversies regarding this issue and suggesting possible future advancements. Among the existing procedures, simple dilation and direct vision internal urethrotomy are more commonly used for short urethral strictures ( <1 cm, soft and no previous intervention. Currently, urethroplasty using buccal mucosa or penile skin is the most widely adopted clinical techniques and have proved successful. Nonetheless, complications such as donor site morbidity remain problem. Tissue engineering techniques are considered as a promising solution for urethral reconstruction, but require further investigation, as does stem cell therapy. Keywords: Anterior urethral strictures, Urethral reconstruction, Tissue engineering, Urethral strictures

  13. Brief cognitive interventions for burn pain.

    Science.gov (United States)

    Haythronthwaite, J A; Lawrence, J W; Fauerbach, J A

    2001-01-01

    This study tested the efficacy of 2 brief cognitive interventions in supplementing regular medical treatment for pain during burn dressing change. Forty-two burn inpatients were randomly assigned to 3 groups: sensory focusing, music distraction, and usual care. Patients reported pain, pain relief satisfaction with pain control, and pain coping strategies. The sensory focusing group reported greater pain relief compared to the music distraction group and a reduction in remembered pain compared to the usual care group, although group differences were not observed on serial pain ratings. In addition, after controlling for burn size and relevant covariates, regression analyses indicated that catastrophizing predicted pain, memory for pain, and satisfaction with pain control. Refinement of the sensory focusing intervention is warranted to reduce catastrophic thinking and improve pain relief

  14. Network Analysis on Attitudes: A Brief Tutorial.

    Science.gov (United States)

    Dalege, Jonas; Borsboom, Denny; van Harreveld, Frenk; van der Maas, Han L J

    2017-07-01

    In this article, we provide a brief tutorial on the estimation, analysis, and simulation on attitude networks using the programming language R. We first discuss what a network is and subsequently show how one can estimate a regularized network on typical attitude data. For this, we use open-access data on the attitudes toward Barack Obama during the 2012 American presidential election. Second, we show how one can calculate standard network measures such as community structure, centrality, and connectivity on this estimated attitude network. Third, we show how one can simulate from an estimated attitude network to derive predictions from attitude networks. By this, we highlight that network theory provides a framework for both testing and developing formalized hypotheses on attitudes and related core social psychological constructs.

  15. The Financial Therapy Association: A Brief History

    Directory of Open Access Journals (Sweden)

    Sonya Britt

    2010-10-01

    Full Text Available The purpose of this brief review is to provide a historical context for the conceptualization, development, and launch of the Financial Therapy Association (FTA. The FTA membership base consists of practicing financial planners, financial counselors, psychologists, marriage and family therapists, social workers, financial coaches, psychotherapists, and researchers from these and other disciplines. From the outset, the Association’s purpose has encompassed five goals:To promote a vision of financial therapy, which is the study of cognitive, emotional, behavioral, relational, economic, and integrative aspects of financial health.To provide a forum for researchers, practitioners, the media, and policy makers to share research and practice methods and models of financial therapy.To promote methods of training for those involved in financial therapy.To inform policy and practice management standards as these relate to financial therapy.To stimulate and disseminate clinical, experimental, and survey research on financial therapy.

  16. Brief overview of geophysical probing technology

    International Nuclear Information System (INIS)

    Ramirez, A.L.; Lytle, R.J.

    1982-01-01

    An evaluation of high-resolution geophysical techniques which can be used to characterize a nulcear waste disposal site is being conducted by the Lawrence Livermore National Laboratory (LLNL) at the request of the US Nuclear Regulatory Commisson (NRC). LLNL is involved in research work aimed at evaluating the current capabilities and limitations of geophysical methods used for site selection. This report provides a brief overview of the capabilities and limitations associated with this technology and explains how our work addresses some of the present limitations. We are examining both seismic and electromagnetic techniques to obtain high-resolution information. We are also assessing the usefulness of geotomography in mapping fracture zones remotely. Finally, we are collecting core samples from a site in an effort to assess the capability of correlating such geophysical data with parameters of interest such as fracture continuity, orientation, and fracture density

  17. Brief description of the Wackersdorf Reprocessing Facility

    International Nuclear Information System (INIS)

    1986-01-01

    The DWK is now planning the construction and operation of a facility for the reprocessing of spent fuel elements and the fabrication of mixed-oxide fuel elements which will initially have an average daily throughput of 2 tons (t) of nuclear fuel. The application required by the Atomic Law was submitted to the Bavarian State Ministry for State Development and Environmental Matters on October 28, 1982. According to Par. 3, Section 1, No. 1 of the Atomic Law Procedural Ordinance such an application for permission in accordance with par. 7 AtL must explicitly be accompanied by a safety report which shall make it possible for third parties to make a judgment whether the impacts associated with the facility and its operation could damage their rights. The safety report is intended to present and explain the concept of the facility, the safety-technological design bases, and the operation of the plant, including its operation and safety systems and the impacts and proposed preventive measures. In addition to the detailed presentations in the safety report, Par. 3 of the Atomic Law Procedural Ordinance also requires a brief description of the plant designed for general public understanding, suitable for the design, which will also explain the expected impacts on the general environment and the surrounding area. Hence the brief description presents and explains the following matters: the site; the technology and state of the art for reprocessing of spent nuclear fuel; the structure and function of the proposed facility; safety provisions of the proposed facility and the management of perturbations in operation; the impacts of the facility and its operation on the environment; measures to be taken for dealing with the radioactive wastes; and provisions for ultimate shut-down of the facility

  18. 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.

  19. 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...

  20. 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…

  1. 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…

  2. 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...

  3. 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).…

  4. 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...

  5. 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.

  6. Canine oral cavity neoplasias - Brief review

    Directory of Open Access Journals (Sweden)

    João Filipe Requicha

    2015-03-01

    Full Text Available ABSTRACT. Requicha J.F., Pires M. dos A., Albuquerque C.M. & Viegas C.A. [Canine oral cavity neoplasias - Brief review.] Neoplasias da cavidade oral do cão - Breve revisão. Revista Brasileira de Medicina Veterinária, 37(1:41-46, 2015. Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande, 1749-024 Lisboa, Portugal e Department of Veterinary Sciences, School of Agriculture and Veterinary Sciences, University of Trás-os-Montes e Alto Douro, P.O. Box 1013, 5001-801 Vila Real, Portugal. E-mail: jfrequicha@gmail.com Oral proliferative lesions are relatively common in domestic carnivores but, fortunately, a lot of these lesions are benign. The oral cavity is place of 6% of all tumours in dogs, being the sixth most important localization of neoplasias in this specie. The non-odontogenic tumors arise from structures of the oral cavity, except from dental tissue, and they are mostly malignant. Odontogenic tumors are those originated from the dental structures. In the case of tumors of non-odontogenic, will be described the oral papillomatosis, the melanoma, the squamous cell carcinoma, and the fibrosarcoma. Among the odontogenic tumors, the focus will be on the epulides, ameloblastoma, odontoma and dentigerous cysts.

  7. History of Hanford Site Defense Production (Brief)

    Energy Technology Data Exchange (ETDEWEB)

    GERBER, M S

    2001-02-01

    This paper acquaints the audience with the history of the Hanford Site, America's first full-scale defense plutonium production site. The paper includes the founding and basic operating history of the Hanford Site, including World War II construction and operations, three major postwar expansions (1947-55), the peak years of production (1956-63), production phase downs (1964-the present), a brief production spurt from 1984-86, the end of the Cold War, and the beginning of the waste cleanup mission. The paper also delineates historical waste practices and policies as they changed over the years at the Hanford Site, past efforts to chemically treat, ''fractionate,'' and/or immobilize Hanford's wastes, and resulting major waste legacies that remain today. This paper presents original, primary-source research into the waste history of the Hanford Site. Finally, the paper places the current Hanford Site waste remediation endeavors in the broad context of American and world history.

  8. Research briefing on high-temperature superconductivity

    Science.gov (United States)

    1987-10-01

    The research briefing was prepared in response to the exciting developments in superconductivity in ceramic oxide materials announced earlier in 1987. The panel's specific charge was to examine not only the scientific opportunities in high-temperature superconductivity but also the barriers to commercial exploitation. While the base of experimental knowledge on the superconductors is growing rapidly, there is as yet no generally accepted theoretical explanation of their behavior. The fabrication and processing challenges presented by the materials suggest that the period or precommercial exploration for applications will probably extend for a decade or more. Near term prospects for applications include magnetic shielding, the voltage standard, superconducting quantum interference devices, infrared sensors, microwave devices, and analog signal processing. The panel also identified a number of longer-term prospects in high-field and large-scale applications, and in electronics. The United States' competitive position in the field is discussed, major scientific and technological objectives for research and development identified, and concludes with a series of recommendations.

  9. A Brief History of Black Holes

    Directory of Open Access Journals (Sweden)

    Crothers S. J.

    2006-04-01

    Full Text Available Neither the layman nor the specialist, in general, have any knowledge of the historical circumstances underlying the genesis of the idea of the Black Hole. Essentially, almost all and sundry simply take for granted the unsubstantiated allegations of some ostentatious minority of the relativists. Unfortunately, that minority has been rather careless with the truth and is quite averse to having its claims corrected, notwithstanding the documentary evidence on the historical record. Furthermore, not a few of that vainglorious and disingenuous coterie, particularly amongst those of some notoriety, attempt to dismiss the testimony of the literature with contempt, and even deliberate falsehoods, claiming that history is of no importance. The historical record clearly demonstrates that the Black Hole has been conjured up by combination of confusion, superstition and ineptitude, and is sustained by widespread suppression of facts, both physical and theoretical. The following essay provides a brief but accurate account of events, verifiable by reference to the original papers, by which the scandalous manipulation of both scientific and public opinion is revealed

  10. Problem based learning - A brief review

    Science.gov (United States)

    Nunes, Sandra; Oliveira, Teresa A.; Oliveira, Amílcar

    2017-07-01

    Teaching is a complex mission that requires not only the theoretical knowledge transmission, but furthermore requires to provide the students the necessary skills for solving real problems in their respective professional activities where complex issues and problems must be frequently faced. Over more than twenty years we have been experiencing an increase in scholar failure in the scientific area of mathematics, which means that Teaching Mathematics and related areas can be even a more complex and hard task. Scholar failure is a complex phenomenon that depends on various factors as social factors, scholar factors or biophysical factors. After numerous attempts made in order to reduce scholar failure our goal in this paper is to understand the role of "Problem Based Learning" and how this methodology can contribute to the solution of both: increasing mathematical courses success and increasing skills in the near future professionals in Portugal. Before designing a proposal for applying this technique in our institutions, we decided to conduct a survey to provide us with the necessary information about and the respective advantages and disadvantages of this methodology, so this is the brief review aim.

  11. Market Brief : Turkey oil and gas pipelines

    International Nuclear Information System (INIS)

    2001-08-01

    This report presented some quick facts about oil and gas pipelines in Turkey and presented opportunities for trade. The key players and customers in the oil and gas sector were described along with an export check list. Turkey is looking into becoming an energy bridge between oil and gas producing countries in the Middle East, Central Asia and Europe. The oil and gas sectors are dominated by the Turkish Petroleum Corporation, a public enterprise dealing with exploration and production, and the State Pipeline Corporation which deals with energy transmission. They are also the key buyers of oil and gas equipment in Turkey. There are several pipelines connecting countries bordering the Caspian Sea. Opportunities exist in the areas of engineering consulting as well as contracting services for oil and gas pipeline transmission and distribution. Other opportunities lie in the area of pipeline construction, rehabilitation, materials, equipment, installation, and supervisory control and data acquisition (SCADA) systems. Currently, the major players are suppliers from Italy, Germany, France, United States and Japan. Turkey has no trade barriers and imported equipment and materials are not subjected to any restriction. The oil and gas market in Turkey expected in increase by an average annual growth rate of 15 per cent from 2001 to 2003. A brief description of pipeline projects in Turkey was presented in this report along with a list of key contacts and support services. 25 refs., 1 append

  12. Briefing highlights space weather risks to GPS

    Science.gov (United States)

    Tretkoff, Ernie

    2011-07-01

    Solar storms, which are expected to increase as the Sun nears the most active phase of the solar cycle, can disrupt a variety of technologies on which society relies. Speakers at a 22 June briefing on Capitol Hill in Washington, D. C., focused on how space weather can affect the Global Positioning System (GPS), which is used in a wide range of industries, including commercial air travel, agriculture, national security, and emergency response. Rocky Stone, chief technical pilot for United Airlines, noted that GPS allows more aircraft to be in airspace, saves fuel, and helps aircraft move safely on runways. “Improvements in space weather forecasting need to be pursued,” he said. Precision GPS has also “changed the whole nature of farming,” said Ron Hatch, Director of Navigation Systems, NavCom Technology/John Deere. GPS makes it possible for tractors to be driven in the most efficient paths and for fertilizer and water to be applied precisely to the areas that most need them. Space weather-induced degradation of GPS signals can cause significant loss to farms that rely on GPS. Elizabeth Zimmerman, Deputy Associate Administrator for the Office of Response and Recovery at the Federal Emergency Management Agency (FEMA), described how FEMA relies on GPS for disaster recovery. The agency is developing an operations plan for dealing with space weather, she said.

  13. A brief history of mathematics in finance

    Directory of Open Access Journals (Sweden)

    Erdinç Akyıldırım

    2014-03-01

    Full Text Available In the list of possible scapegoats for the recent financial crises, mathematics, in particular mathematical finance has been ranked, without a doubt, as the first among many and quants, as mathematicians are known in the industry, have been blamed for developing and using esoteric models which are believed to have caused the deepening of the financial crisis. However, as Lo and Mueller (2010 state “Blaming quantitative models for the crisis seems particularly perverse, and akin to blaming arithmetic and the real number system for accounting fraud.” Throughout the history, mathematics and finance have always been in a close relationship. Starting from Babylonians, through Thales, and then Fibonacci, Pascal, Fermat, Bernoulli, Bachelier, Wiener, Kolmogorov, Ito, Markowitz, Black, Scholes, Merton and many others made huge contributions to the development of mathematics while trying to solve finance problems. In this paper, we present a brief historical perspective on how the development of finance theory has influenced and in turn been influenced by the development of mathematical finance theory.

  14. 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.

  15. '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.

  16. 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.

  17. Legal briefing: conscience clauses and conscientious refusal.

    Science.gov (United States)

    Pope, Thaddeus Mason

    2010-01-01

    This issue's "Legal Briefing" column covers legal developments pertaining to conscience clauses and conscientious refusal. Not only has this topic been the subject of recent articles in this journal, but it has also been the subject of numerous public and professional discussions. Over the past several months, conscientious refusal disputes have had an unusually high profile not only in courthouses, but also in legislative and regulatory halls across the United States. Healthcare providers' own moral beliefs have been obstructing and are expected to increasingly obstruct patients' access to medical services. For example, some providers, on ethical or moral grounds, have denied: (1) sterilization procedures to pregnant patients, (2) pain medications in end-of-life situations, and (3) information about emergency contraception to rape victims. On the other hand, many healthcare providers have been forced to provide medical treatment that is inconsistent with their moral beliefs. There are two fundamental types of conscientious objection laws. First, there are laws that permit healthcare workers to refuse providing - on ethical, moral, or religious grounds healthcare services that they might otherwise have a legal or employer-mandated obligation to provide. Second, there are laws directed at forcing healthcare workers to provide services to which they might have ethical, moral, or religious objections. Both types of laws are rarely comprehensive, but instead target: (1) certain types of healthcare providers, (2) specific categories of healthcare services, (3) specific patient circumstances, and (4) certain conditions under which a right or obligation is triggered. For the sake of clarity, I have grouped recent legal developments concerning conscientious refusal into eight categories: 1. Abortion: right to refuse 2. Abortion: duty to provide 3. Contraception: right to refuse 4. Contraception: duty to provide 5. Sterilization: right to refuse 6. Fertility, HIV, vaccines

  18. A brief examination of optical tagging technologies.

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann, Mark R.; Cahill, Paul A. (Aspecular Optics, Dayton, OH); Drummond, Timothy J.; Wilcoxon, Jess Patrick

    2003-07-01

    Presented within this report are the results of a brief examination of optical tagging technologies funded by the Laboratory Directed Research and Development (LDRD) program at Sandia National Laboratories. The work was performed during the summer months of 2002 with total funding of $65k. The intent of the project was to briefly examine a broad range of approaches to optical tagging concentrating on the wavelength range between ultraviolet (UV) and the short wavelength infrared (SWIR, {lambda} < 2{micro}m). Tagging approaches considered include such things as simple combinations of reflective and absorptive materials closely spaced in wavelength to give a high contrast over a short range of wavelengths, rare-earth oxides in transparent binders to produce a narrow absorption line hyperspectral tag, and fluorescing materials such as phosphors, dies and chemically precipitated particles. One technical approach examined in slightly greater detail was the use of fluorescing nano particles of metals and semiconductor materials. The idea was to embed such nano particles in an oily film or transparent paint binder. When pumped with a SWIR laser such as that produced by laser diodes at {lambda}=1.54{micro}m, the particles would fluoresce at slightly longer wavelengths, thereby giving a unique signal. While it is believed that optical tags are important for military, intelligence and even law enforcement applications, as a business area, tags do not appear to represent a high on return investment. Other government agencies frequently shop for existing or mature tag technologies but rarely are interested enough to pay for development of an untried technical approach. It was hoped that through a relatively small investment of laboratory R&D funds, enough technologies could be identified that a potential customers requirements could be met with a minimum of additional development work. Only time will tell if this proves to be correct.

  19. 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.

  20. 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...

  1. 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.

  2. 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

  3. Brief Report Teachers' work as appreciated by pupils, parents ...

    African Journals Online (AJOL)

    Brief Report Teachers' work as appreciated by pupils, parents, department heads and principals. ... Open Access DOWNLOAD FULL TEXT Subscription or Fee ... one does contributes to job satisfaction which in turn leads to a high level of

  4. 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)

  5. 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.

  6. 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.

  7. FREE Policy Brief No. 3 - Women's Football and Female Fans

    DEFF Research Database (Denmark)

    Pfister, Gertrud Ursula; Sonntag, Albrecht; Ranc, David

    2015-01-01

    Football Research in an Enlarged Europe (FREE). This is the third of three policy briefs based on findings from the FREE project. It summarises results from the project's research stream on the feminisation of football....

  8. Brief Introduction to Hepatitis B for Parents of Adopted Children

    Science.gov (United States)

    Brief Introduction to Hepatitis B for Parents of Adopted Children by Sarah Jane Schwarzenberg, MD What is hepatitis B? ... injury will also need careful medical management. In short, prospective par- ents of children with hepatitis B ...

  9. 17 CFR 10.82 - Proposed findings and conclusions; briefs.

    Science.gov (United States)

    2010-04-01

    ... generally follow the same style as prescribed for the initial brief but may omit a statement of the case if... on the record, with exact citations to the transcripts of record and exhibits in support of each...

  10. The Effects of Brief Psychotherapy of Coping with Breast Cancer

    National Research Council Canada - National Science Library

    McCaul, Kevin

    1997-01-01

    .... Our novel approach tested the effects of brief psychotherapy provided by phone. The final sample included 61 women newly diagnosed with breast cancer who were randomly assigned to either the phone treatment or a "standard treatment" condition...

  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. Zora’s Politics: A Brief Introduction

    Directory of Open Access Journals (Sweden)

    Ernest Julius Mitchell II

    2013-09-01

    Full Text Available In his introduction to reading Zora Neale Hurston’s politics, Mitchell argues that contemporary scholarship has misread Hurston in significant ways, distorting Hurston’s work and reputation to serve contesting political agendas; thus, in recent years, she has been associated with “a bewildering array of affiliations: republican, libertarian, radical democrat, reactionary conservative, black cultural nationalist, anti-authoritarian feminist, and woman-hating protofascist.” Recuperating Hurston from this impossible political melee of labels, Mitchell argues, requires a careful reading of Hurston’s work dating from her earliest pieces in the late 1920s, as well as surveying her many yet to be published manuscripts and letters; it requires recognition of the transnational and comparative lens through which she reported on political maneuvers and military histories, as well as reading not only her strong criticisms but also her silences, ironic phrasings, and nuanced critiques in her writings on global colonial enterprises. Mitchell’s introduction to the two Hurston essays here reprinted, “I Saw Negro Votes Peddled” (1950 and “Why the Negro Won’t Buy Communism” (1951—courtesy of the American Legion Magazine—is set in the larger frame of his assertion that Hurston’s work should be read with a deep appreciation of her staunch anticolonialism. Tracing her political philosophy through her views of how race and religion are used to valorize an international culture of violence that serves imperialistic and colonial ends, Mitchell takes his reader on a tour of Hurston’s transnational commentary—from the US occupation of Haiti, to the Spanish and British on the Florida peninsula; from Communist Russia and China, to election practices in the US—to set the stage for our encounters with these rarely read Hurston essays. Reading Mitchell’s “Zora’s Politics: A Brief Introduction” provides a firm foundation for a more

  13. Global Green New Deal. Policy Brief

    International Nuclear Information System (INIS)

    2009-03-01

    The 'Global Green New Deal' (GGND) presented here has three broad objectives. It should make a major contribution to reviving the world economy, saving and creating jobs, and protecting vulnerable groups. It should promote sustainable and inclusive growth and the achievement of the MDGs, especially ending extreme poverty by 2015. Also, it must reduce carbon dependency and ecosystem degradation. These are key risks along a path to a sustainable world economy. Our consultations and our commissioned research, summarized here in this Policy Brief, make a strong case for the active 'greening' of proposed fiscal stimulus packages. However, this must also be backed by necessary changes in international and domestic policy architectures, as the current framework is biased in favour of resurrecting an unsustainable 'brown economy'. Our proposals are therefore grouped under three categories - targeted stimulus spending in 2009-10, changes in domestic policies, and changes in international policy architecture. Furthermore, we recognize that many less developed countries do not have the resources of their own and will have to rely on foreign aid and support, both financial and non-financial. We propose that the fiscal stimulus (to be applied over 2009 and 2010) should prioritize energy efficient buildings and investments in sustainable transport and renewable energy. Developing countries should prioritize investment in agricultural productivity measures, freshwater management, and sanitation, as these have demonstrable and exceptional social returns. Domestic policy reforms are recommended to substantially reduce perverse subsidies (eg: fossil fuels) and instead to create positive incentives and appropriate taxes which will encourage a greener economy. Domestic reforms should also address some common issues in land use and urban policy. Integrated management of freshwater would also require some domestic policy changes, and this should be prioritized by developing countries

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

    Directory of Open Access Journals (Sweden)

    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  4. Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

    International Nuclear Information System (INIS)

    Finger, Paul T.

    2008-01-01

    Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

  5. The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Simonds, Jana; Miller, Frank; Mandel, Jess; Davidson, Terence M

    2009-05-01

    Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. Retrospective pilot study. Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

  6. Fermi GBM transient searches with ADWO

    Czech Academy of Sciences Publication Activity Database

    Bagoly, Z.; Szécsi, Dorottya; Balázs, L.G.; Csabai, I.; Dobos, L.; Horváth, I.; Lichtenberger, J.; Tóth, L.V.

    2017-01-01

    Roč. 47, č. 2 (2017), s. 76-83 ISSN 1335-1842. [INTEGRAL/BART Workshop /14./. Karlovy Vary, 03.04.2017-07.04.2017] R&D Projects: GA ČR GA13-10589S Institutional support: RVO:67985815 Keywords : gravitational wave s * gamma rays bursts * ADWO Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science) Impact factor: 0.336, year: 2016

  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. IDRC at 40: A Brief History | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-01-24

    Jan 24, 2011 ... In celebration of 40 years of research for development, IDRC is pleased to announce the publication of IDRC at 40: A Brief History. The 32-page booklet traces IDRC's history through the decades, from the earliest discussions of establishing a research centre focused on technology and development, to the ...

  9. Does brief Aikido training reduce aggression of youth?

    Science.gov (United States)

    Delva-Tauiliili, J

    1995-02-01

    Over 2 1/2 weeks, 21 youth trained in beginning principles of Aikido were not rated lower on the Teachers' Self-control Rating Scale and on aggressive behavior than 21 students on a waiting list for a class; however, the several methodological limitations suggested conclusions on the effects of brief Aikido training on youths' aggressive behaviors are premature.

  10. Class Size Reduction: Great Hopes, Great Challenges. Policy Brief.

    Science.gov (United States)

    WestEd, San Francisco, CA.

    This policy brief examines the benefits and the challenges that accompany class-size reduction (CSR). It suggests that when designing CSR programs, states should carefully assess specific circumstances in their schools as they adopt or modify CSR efforts to avoid the unintended consequences that some programs have experienced. Some of the…

  11. Organizational Culture and Internationalization: A Brief Literature Review

    Science.gov (United States)

    Nussbaumer, Alison

    2013-01-01

    This brief literature review introduces an area of emerging research about the impact of organizational culture on institutional strategies for internationalization. The review begins by introducing the concept of organizational culture, particularly within higher education. Five articles published between 2003 and 2012 are examined that introduce…

  12. Examining a Brief Measure of Parent Involvement in Children's Education

    Science.gov (United States)

    Lau, Won-Fong K.

    2013-01-01

    The current study is a preliminary investigation of the psychometric properties of a brief seven-item Parent Involvement Survey (PIS) as developed by the researcher, that could potentially be used in schools. In an effort to test for construct validity, the relation of the PIS to elementary-aged students' receptive vocabulary skills and four…

  13. Information Brief on Green Power Marketing, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    Sweezey, B.; Houston, A.

    1998-02-01

    This document is the second in a series of information briefs on green power marketing activity in the United States. It includes descriptions of utility green pricing programs, green power marketing activity, retail access legislation and pilot programs, and other data and information supporting the development of green power markets.

  14. 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.

  15. Why September Matters: Improving Student Attendance. Policy Brief

    Science.gov (United States)

    Olsen, Linda S.

    2014-01-01

    This brief examines absences in September and students' attendance over the rest of the year. Attendance should be addressed before it becomes problematic. Chronic absenteeism, missing more than 20 days of a school year, is an early indicator of disengagement. High absence rates have negative consequences not only for individual students, but also…

  16. International Briefing 34: Training and Development in Spain

    Science.gov (United States)

    Rigby, Mike; Ponce Sanz, Yolanda

    2016-01-01

    This article locates training and development in Spain within the country's socio-economic context. It maps the major changes which have been introduced into the training and development system since the briefing by Escardíbul and Llinas-Audet published in this journal in 2010. It relates those changes to the ongoing economic crisis which began in…

  17. Brief encounters with qualitative methods in health research: conversation analysis

    OpenAIRE

    Miller, Paul K.

    2016-01-01

    This paper provides a brief introductory outline of the conversation analytic method, and some of its applications in health research. Drawing on extant literature and an illustrative original case study of suicide risk-assessment in primary care, the core tenets and techniques of the approach are described.

  18. The Chalk River Nuclear Laboratories contingency plan -a brief description

    International Nuclear Information System (INIS)

    White, J.M.

    1982-01-01

    A brief description of the contingency plan which deals with both the on-site and off-site consequences of a serious nuclear accident is given. The off-site consequences of different size releases and the subsequent action taken by employees, radiation protection experts, municipal, Provincial and Federal authorities is described and the interaction of the various groups is discussed. (author)

  19. Developing and Implementing the Qatar Student Assessment System. Research Brief

    Science.gov (United States)

    Gonzalez, Gabriella; Le, Vi-Nhuan; Broer, Markus; Mariano, Louis T.; Froemel, J. Enrique; Goldman, Charles A.; DaVanzo, Julie

    2009-01-01

    This research brief summarizes the development of a standards-based student assessment system in Qatar, lessons for policymakers in Qatar and elsewhere, and challenges in aligning the assessment with future changes in the curriculum standards. Analysis of Qatar's standards-based student assessment system, the first in the region, offers several…

  20. Initial Educational Experiences of Tertiary Students. LSAY Briefing Number 14

    Science.gov (United States)

    Hillman, Kylie

    2008-01-01

    This "Briefing" presents information about the initial tertiary education experiences, such as satisfaction with aspects of student life and changes to initial enrolments, of two groups of young people, based on two recent Longitudinal Surveys of Australian Youth (LSAY) research reports. One study focused on the first year experiences of…

  1. Toys in Physics Lectures and Demonstrations--A Brief Review

    Science.gov (United States)

    Guemez, J.; Fiolhais, C.; Fiolhais, M.

    2009-01-01

    The use of toys in physics teaching is common. This brief review of the physics of toys intends to show that they are not only very useful in lectures and demonstrations in order to motivate students but also very interesting from a scientific point of view. However, since their physics is sometimes too cumbersome, the effect can be the opposite.…

  2. Brief psychotic disorder in a middle aged Nigerian following the ...

    African Journals Online (AJOL)

    This case report illustrates the sudden onset, brief course and remission of a psychotic illness in a middle-aged Nigerian starting soon after she heard about the terrorist attacks in America. Vulnerability factors including personality traits and other concurrent life events were identified in the patients. Common mental disorder ...

  3. A Brief Illustrated Guide to Understanding Islam. Second Edition.

    Science.gov (United States)

    Ibrahim, I. A.

    This book is a brief guide to understanding Islam, intended to help individuals better understand Islamic culture, Muslims, and the Holy Quran. It consists of the following three chapters: (1) Some Evidence for the Truth of Islam; (2) Some Benefits of Islam; and (3) General Information on Islam. The book is extensively illustrated with photographs…

  4. 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

  5. Prostate specific antigen - brief update on its clinical use | Heyns ...

    African Journals Online (AJOL)

    Prostate specific antigen - brief update on its clinical use. ... (45 years in those with a family history of prostate cancer and – possibly – African men); ... PSA doubling time (the period it takes for the PSA to double) correlates with the prognosis ...

  6. Brief history of patient safety culture and science.

    Science.gov (United States)

    Ilan, Roy; Fowler, Robert

    2005-03-01

    The science of safety is well established in such disciplines as the automotive and aviation industry. In this brief history of safety science as it pertains to patient care, we review remote and recent publications that have guided the maturation of this field that has particular relevance to the complex structure of systems, personnel, and therapies involved in caring for the critically ill.

  7. 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.

  8. A Brief Social Skills Intervention to Reduce Challenging Classroom Behavior

    Science.gov (United States)

    McDaniel, Sara C.; Bruhn, Allison L.; Troughton, Leonard

    2017-01-01

    Social skills instruction has been recommended as a way of improving behavioral and social outcomes for students with emotional and behavioral disorders (EBD). A brief social skills intervention ("Stop and Think" (Knoff in "The stop & think social skills program," Sopris West, Longmont, CO, 2001) was used to extend the…

  9. Enrichment in Massachusetts Expanded Learning Time (ELT) Schools. Issue Brief

    Science.gov (United States)

    Caven, Meghan; Checkoway, Amy; Gamse, Beth; Luck, Rachel; Wu, Sally

    2012-01-01

    This brief highlights key information about enrichment activities, which represent one of the main components of the Massachusetts Expanded Learning Time (ELT) initiative. Over time, the ELT initiative has supported over two dozen schools across the Commonwealth. A comprehensive evaluation of the ELT initiative found that implementation of the…

  10. An Update on the "Cycle of Violence." Research in Brief.

    Science.gov (United States)

    Widom, Cathy S.; Maxfield, Michael G.

    This brief updates a longitudinal study comparing the arrest records of abused and neglected children with arrest records of non-abused or neglected children. Subjects included 908 substantiated cases of childhood abuse or neglect processed by the courts from 1967-71 who were matched by sex, age, race, and family socioeconomic status with 667…

  11. Physiological effects after exposure to heat : A brief literature review

    NARCIS (Netherlands)

    Bogerd, C.P.; Daanen, H.A.M.

    2011-01-01

    Many employees are exposed to heat stress during their work. Although the direct effects of heat are well reported, the long term physiological effects occurring after heat exposure are hardly described. The present manuscript addresses these issues in the form of a brief literature review. Repeated

  12. A validation study of the Brief Irrational Thoughts Inventory

    NARCIS (Netherlands)

    Hoogsteder, L.M.; Wissink, I.B.; Stams, G.J.J.M.; van Horn, J.E.; Hendriks, J.

    2014-01-01

    This study examines the reliability and validity of the "Brief Irrational Thoughts Inventory" (BITI) in a sample of 256 justice-involved youths. The BITI is a questionnaire used to determine the nature and severity of irrational thoughts related to aggressive (externalizing), sub-assertive

  13. Towards the european strategy for particle physics : The briefing book

    NARCIS (Netherlands)

    Akesson, T.; Aleksan, R.; Allanach, B.; Bertolucci, S.; Blondel, A.; Butterworth, J.; Cavalli-Sforza, M.; Cervera, A.; de Naurois, M.; Desch, K.; Egede, U.; Heuer, R.; Hoecker, A.; Huber, P.; Jungmann, K.; Linde, F.; Lombardi, A.; Mangano, M.; Mezzetto, M.; Onderwater, G.; Palanque-Delabrouille, N.; Peach, K.; Polosa, A.; Rondio, E.; Webber, B.; Weiglein, G.; Womersley, J.

    This document was prepared as part of the briefing material for the Workshop of the CERN Council Strategy Group, held in DESY Zeuthen from 2nd to 6th May 2006. It gives an overview of the physics issues and of the technological challenges that will shape the future of the field, and incorporates

  14. What patient characteristics make clinicians recommend brief treatment?

    NARCIS (Netherlands)

    Schaefer, B. A.; Koeter, M. W. J.; Wouters, L.; Emmelkamp, P. M. G.; Schene, A. H.

    2003-01-01

    Objective: Assessing self-rated items that might have an impact on clinicians recommending brief treatment (BT) over unlimited or long-term treatment (ULT). Method: On the basis of patient self-report data we compared patients referred by clinicians to BT (n =71) with those referred to ULT (n =145).

  15. Infants Learn Phonotactic Regularities from Brief Auditory Experience.

    Science.gov (United States)

    Chambers, Kyle E.; Onishi, Kristine H.; Fisher, Cynthia

    2003-01-01

    Two experiments investigated whether novel phonotactic regularities, not present in English, could be acquired by 16.5-month-olds from brief auditory experience. Subjects listened to consonant-vowel-consonant syllables in which particular consonants were artificially restricted to either initial or final position. Findings in a subsequent…

  16. Validation of the Marijuana Effect Expectancy Questionnaire-Brief

    Science.gov (United States)

    Torrealday, O.; Stein, L. A. R.; Barnett, N.; Golembeske, C.; Lebeau, R.; Colby, S. M.; Monti, P. M.

    2008-01-01

    The purpose of this study was to evaluate a brief version of the Marijuana Effect Expectancy Questionnaire (MEEQ; Schafer & Brown, 1991). The original MEEQ was reduced to 6 items (MEEQ-B). Principal component analysis (PCA) was performed and two factors were identified (positive effects and negative effects) accounting for 52.3% of the variance.…

  17. The Internet: A Primer. House Research Information Brief.

    Science.gov (United States)

    Dalton, Pat

    This paper, one in a series of information briefs related to the Internet and taxation, contains a simplified overview of the Internet and a glossary of terms that are commonly encountered in discussing the Internet. Terms that are included in this glossary are italicized when they are used elsewhere in the paper. A series of questions are asked…

  18. Brief Classroom Training Sessions for Workplace Readiness: Are They Effective?

    Science.gov (United States)

    Palesy, Debra

    2017-01-01

    Classroom training sessions for new home care workers (HCWs) are often brief and ad hoc, varying in format and content. Yet the application of this training may be central to worker and client safety. A qualitative approach was adopted for this inquiry, comprising two separate but related practical studies. In the first, exploratory study,…

  19. Developing Social Competence in Children. Choices Briefs, Number 3.

    Science.gov (United States)

    Schwartz, Wendy

    This brief presents an overview of effective strategies for developing prosocial attitudes and behaviors in elementary school children. The description of approaches and activities can help educators integrate an antiviolence education program into their schools and classrooms, select a program to implement from many models in use around the…

  20. A Review of the Brief Multidimensional Students' Life Satisfaction Scale

    Science.gov (United States)

    Huebner, E. Scott; Seligson, Julie L.; Valois, Robert F.; Suldo, Shannon M.

    2006-01-01

    There are few psychometrically sound measures of life satisfaction suitable for children and adolescents. The purpose of this paper is to describe the rationale, development, and psychometric properties of a brief multidimensional life satisfaction scale appropriate for use with children of ages 8-18. The paper summarizes extant studies of its…

  1. 78 FR 17233 - Notice of Opportunity To File Amicus Briefs

    Science.gov (United States)

    2013-03-20

    .... See Bohac v. Department of Agriculture, 239 F.3d 1334, 1337-43 (Fed. Cir. 2001). However, under.... Any commonly-used word processing format or PDF format is acceptable; text formats are preferable to image formats. Briefs may also be filed with the Office of the Clerk of the Board, Merit Systems...

  2. Islet neogenesis is stimulated by brief occlusion of the main ...

    African Journals Online (AJOL)

    Islet neogenesis is stimulated by brief occlusion of the main pancreatic duct. ... South African Medical Journal ... where the initial events that culminate in increased pancreatic endocrine mass caube studied. ... The animals were killed 56 days post .occlusion, and the pancreata excised and fiXed tor histological analysis.

  3. Training Staff to Implement Brief Stimulus Preference Assessments

    Science.gov (United States)

    Weldy, Christina R.; Rapp, John T.; Capocasa, Kelli

    2014-01-01

    We trained 9 behavioral staff members to conduct 2 brief preference assessments using 30-min video presentations that contained instructions and modeling. After training, we evaluated each staff member's implementation of the assessments in situ. Results indicated that 1 or 2 training sessions for each method were sufficient for teaching each…

  4. Childhood Antecedents to Adult Coronary Artery Diseases. Special Reference Briefs.

    Science.gov (United States)

    Winick, Myron

    This reference brief deals with the childhood antecedents to atherosclerosis and hypertension. While diet is related to the development of coronary artery diseases, there is some disagreement about what dietary changes are necessary or desirable in children to prevent their development, and at what age such changes should be made. Fifty-five…

  5. Should Everyone Go to College? CCF Brief #50

    Science.gov (United States)

    Owen, Stephanie; Sawhill, Isabel

    2013-01-01

    In this brief, the authors have corralled existing research to make the point that while on average the return to college is highly positive, there is a considerable spread in the value of going to college. A bachelor's degree is not a smart investment for every student in every circumstance. The authors have outlined three important steps…

  6. Part C Service Coordination: State Policies and Models. Synthesis Brief.

    Science.gov (United States)

    Markowitz, Joy

    This brief paper summarizes data from a survey of state coordinators of Part C of the Individuals with Disabilities Education Act concerning service coordination to infants and toddlers with disabilities. The survey examined variations in service coordination at the state level including roles of parents, values of key stakeholders, sources of…

  7. Change of patients' perceptions of telemedicine after brief use

    NARCIS (Netherlands)

    Cranen, Karlijn; Cranen, Karlijn; Huis in 't Veld, M.H.A.; IJzerman, Maarten Joost; Vollenbroek-Hutten, Miriam Marie Rosé

    Objective: This study aims to investigate whether patients' perceptions regarding a Web-based telemedicine service, for instruction and monitoring of an exercise program, change after brief use. Materials and Methods: Thirty patients were allocated, matched on gender and age, to a control group (10)

  8. A brief measure of social media self-control failure

    NARCIS (Netherlands)

    Du, Jie; van Koningsbruggen, Guido M.; Kerkhof, Peter

    People often fail in controlling their social media use when it conflicts with other goals and obligations. To facilitate research on understanding social media self-control failures, we constructed a brief social media self-control failure (SMSCF)-scale to assess how often social media users give

  9. Keeping Young People in (Vocational) Education: What Works? Briefing Note

    Science.gov (United States)

    Cedefop - European Centre for the Development of Vocational Training, 2013

    2013-01-01

    Too many young people leave education (including vocational education) too soon. Yet early leavers are at greater risk of long-term unemployment, poverty and crime, and now cost the European economy 1.25% of GDP. This brief report looks at the reasons why young people leave and what could be done to end this trend. Considerations for policy-makers…

  10. 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...

  11. 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

  12. 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

  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 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.

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. A brief status of non-standard neutrino interactions

    International Nuclear Information System (INIS)

    Ohlsson, Tommy

    2013-01-01

    In this plenary talk, we review the status of non-standard neutrino interactions (NSIs). First, we give a brief introduction to neutrino flavor transitions with NSIs based on the standard paradigm of neutrino oscillations. Then, we discuss alternative scenarios for neutrino flavor transitions such as neutrino decoherence, neutrino decay, and NSIs. Second, we investigate NSIs with three neutrino flavors. In general, we introduce production and detection NSIs, including the so-called zero-distance effect, and matter NSIs. In addition, we study mappings and approximate formulas for NSIs. Third, we present a brief account of theoretical models for NSIs. Fourth and most important, we investigate in detail the phenomenology of NSIs based on different types of data from neutrino experiments. Fifth, we give some phenomenological bounds on both matter and production/detection NSIs as well as we present sensitivity and discovery reach of NSIs at future experiments. Finally, we present a summary and state our conclusions

  2. Brief overview of BioMicroNano Technologies.

    Energy Technology Data Exchange (ETDEWEB)

    Gourley, Paul Lee

    2005-01-01

    This paper provides a brief overview of the fields of biological micro-electromechanical systems (bioMEMs) and associated nanobiotechnologies, collectively denoted as BioMicroNano. Although they are developing at a very rapid pace and still redefining themselves, several stabilized areas of research and development can be identified. Six major areas are delineated, and specific examples are discussed and illustrated. Various applications of the technologies are noted, and potential market sizes are compared.

  3. Brief report on Open Praxis figures and data (2017

    Directory of Open Access Journals (Sweden)

    Inés Gil-Jaurena

    2018-02-01

    Full Text Available In the first Open Praxis issue in 2018 we briefly report on some statistics and information about Open Praxis development. The report covers the period January 2013 - December 2017, with a special focus in volume 9, published in 2017. After the brief report, what follows is an introduction to the first Open Praxis issue in volume 10, which includes six articles in the research papers section and two innovative practice papers.

  4. 2015 Relaunch as Open Access Pediatric Neurology Briefs

    OpenAIRE

    Millichap, John J.; Millichap, J. Gordon

    2015-01-01

    Pediatric Neurology Briefs (PNB) has been published monthly since 1987 as a continuing education service designed to expedite and facilitate review of current medical literature concerning pediatric neurology. In 2015, PNB is relaunched as an open access, peer-reviewed, journal with an expanded editorial board.  PNB has a new website and content management system capable of organizing peer-review and providing improved...

  5. Israel: Background and U.S. Relations in Brief

    Science.gov (United States)

    2017-02-24

    of the March 2015 Israeli electoral campaign, Netanyahu says that a Palestinian state will not be established under his watch, but after the elections...www.state.gov/p/nea/rls/rpt/259262.htm. It also lamented terrorist attacks against civilians and Palestinian incitement to violence . 29 The...U.S. Relations in Brief Congressional Research Service 10  Calls for immediate steps to prevent acts of violence against civilians and to

  6. The nature of light. A brief introduction to photochemistry

    OpenAIRE

    Font, Josep

    2017-01-01

    The first lecture of the seminar on Light, Darkness and Living Beings, held in Mataró in March 2015, was devoted to explaining the dual nature of light and the interaction of this electromagnetic radiation with matter, considering mainly the photochemical aspects. This article summarizes the lecture, offering a brief description of the basis of photochemistry and giving some examples of reactions that need light in order to occur. Examples related to biological systems (e.g. plant photosynthe...

  7. A brief scenario about the ''space pollution'' around the Earth

    International Nuclear Information System (INIS)

    Brito, T P; Celestino, C C; Moraes, R V

    2013-01-01

    In this work is presented a brief review about the main events generating of space debris around the Earth, occurred up to the present day. How the clouds of debris ''polluted'' the neighborhood of orbits in which the bodies were initially allocated is here analyzed. The implications of the growth of space debris existing on space missions as well as safety rules to control sources of debris are discussed

  8. Briefing Highlights Vulnerability of GPS to Adverse Space Weather

    Science.gov (United States)

    Balcerak, Ernie

    2011-08-01

    Through its effects on GPS and other technologies, space weather can affect a variety of industries, including agriculture, commercial air travel, and emergency response. Speakers focused on these topics at a 22 June briefing on Capitol Hill in Washington, D. C. Solar flares can produce radio bursts that directly interfere with GPS signals. Solar activity can also cause ionospheric disturbances that produce distortions and delays in GPS signals, degrading the accuracy of positioning and navigation systems.

  9. Briefing book on environmental and waste management activities

    International Nuclear Information System (INIS)

    Quayle, T.A.

    1993-04-01

    The purpose of the Briefing Book is to provide current information on Environmental Restoration and Waste Management Activities at the Hanford Site. Each edition updates the information in the previous edition by deleting those sections determined not to be of current interest and adding new topics to keep up to date with the changing requirements and issues. This edition covers the period from October 15, 1992 through April 15, 1993

  10. Control of autonomous ground vehicles: a brief technical review

    Science.gov (United States)

    Babak, Shahian-Jahromi; Hussain, Syed A.; Karakas, Burak; Cetin, Sabri

    2017-07-01

    This paper presents a brief review of the developments achieved in autonomous vehicle systems technology. A concise history of autonomous driver assistance systems is presented, followed by a review of current state of the art sensor technology used in autonomous vehicles. Standard sensor fusion method that has been recently explored is discussed. Finally, advances in embedded software methodologies that define the logic between sensory information and actuation decisions are reviewed.

  11. A brief family and academic biography of Benson E. Ginsburg.

    Science.gov (United States)

    Maxson, Stephen C

    2011-11-01

    This is a brief personal biography of Benson E. Ginsburg, my friend, colleague and mentor. This is personal in several ways. First, it is about Benson's family as well as his career. Second, much of what I write is based on discussions with Benson. Third, after 1960, Benson's story is a big part of my story. I have been there for more than 50 years as it has unfolded.

  12. A Brief Description of Ceremony Mangongkal Holi in Toba Batak

    OpenAIRE

    Pardosi, Rafael

    2011-01-01

    Judul kertas karya ini adalah A Brief Description of Ceremony of Mangongkal Holi in Toba Batak. Mangongkal holi adalah suatu upacara yang dilakukan oleh orang batak terutama suku Batak Toba dengan mengali kembali kuburan nenek moyangnya dan kemudian mengumpulkan seluruh tulang-tulangnya dan kemudian dipindahkan ketempat yang baru atau disebut dengan tugu. Kertas karya ini menjelaskan tentang pengertian dari mangongkal holi serta tata cara jalannya upacara tersebut. Selain itu juga, dalam kert...

  13. STS 51-L crewmembers briefed during training session

    Science.gov (United States)

    1986-01-01

    Five members of the STS 51-L crew and a backup crewmember are briefed during a training session in JSC's Shuttle mockup and integration laboratory. From left to right are Astronauts Ellison S. Onizuka, mission specialist; Ronald E. McNair, mission specialist; Gregory Jarvis, Hughes payload specialist; Judith A. Resnik, mission specialist; Sharon Christa McAuliffe, citizen observer/payload specialist representing the Teacher in Space project. Barbara R. Morgan, backup to McAuliffe, is in the right foreground.

  14. FACTOR STRUCTURE OF THE BRIEF NEGATIVE SYMPTOM SCALE

    OpenAIRE

    Strauss, Gregory P.; Hong, L. Elliot; Gold, James M.; Buchanan, Robert W.; McMahon, Robert P.; Keller, William R.; Fischer, Bernard A.; Catalano, Lauren T.; Culbreth, Adam J.; Carpenter, William T.; Kirkpatrick, Brian

    2012-01-01

    The current study examined the factor structure of the Brief Negative Symptom Scale (BNSS), a next-generation negative symptom rating instrument developed in response to the NIMH-sponsored Consensus Development Conference on Negative Symptoms. Participants included 146 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Principal axis factoring indicated two distinct factors explaining 68.7% of the variance. Similar to previous findings, the factors reflected mot...

  15. A brief history of time a reader's companion

    CERN Document Server

    1992-01-01

    In 1989 Anglia Television joined with Steven Spielberg's Amblin Entertainment, NBC and the Tokyo Broadcasting System to announce production of a 90-minute feature on the life of Stephen Hawking and his book "A Brief History of Time". The film that resulted highlights the visual demonstration of Hawking's theories and this book provides an accompaniment to this film as well as a biography of Hawking's life, including his battle against motor neurone disease.

  16. Leadership: briefing and debriefing in the operating room.

    Science.gov (United States)

    Donnelly, Teresa

    2017-07-01

    Steelman (2014) stated that the concept of briefing and debriefing used in operating theatres derived from the airline industry in the 1970s. There had been a series of devastating air crashes and the airline industry had come under severe public scrutiny. Investigations identified that, while the crews operating these aircrafts were very skilled and knowledgeable, they lacked competence in their ability to perform as part of a team. Copyright the Association for Perioperative Practice.

  17. 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.

  18. Brief Psychotherapy for Maternal Depression: Impact on Mothers and Children.

    Science.gov (United States)

    Swartz, Holly A; Cyranowski, Jill M; Cheng, Yu; Zuckoff, Allan; Brent, David A; Markowitz, John C; Martin, Stacy; Amole, Marlissa C; Ritchey, Fiona; Frank, Ellen

    2016-06-01

    Two-generation studies demonstrate that treating maternal depression benefits school-age children. Although mothers prefer psychotherapy to medication, little is known about how psychotherapy for maternal depression affects offspring, especially in very high-risk families in which both mothers and children concurrently meet syndromal criteria for psychiatric disorders. This trial evaluated the effects of 2 brief psychotherapies for maternal depression on very high-risk families. Mothers with major depressive disorder were randomly assigned to 9 sessions of either brief interpersonal psychotherapy for mothers (IPT-MOMS; n = 85) or brief supportive psychotherapy (BSP; n = 83). Independent assessors evaluated mothers and their children, ages 7 to 18 years, diagnosed with at least 1 internalizing disorder, every 3 months over the course of 1 year. Symptoms and functioning of mothers and children improved significantly over time, with no between-group differences. However, children of mothers assigned to BSP had more outpatient mental health visits and were more likely to receive antidepressant medication. Mothers reported greater satisfaction with IPT-MOMS than BSP. Improvement in mothers' depressive symptoms was associated with improvement in child functioning in time-lagged fashion, with children improving 3 to 6 months after mothers improved. Antidepressant medication use and number of mental health visits received by children did not affect outcomes. IPT-MOMS and BSP demonstrated comparable beneficial effects on maternal depression. Children's functioning improved following maternal improvement, independent of youths' treatment. Children of mothers randomized to IPT-MOMS, compared with BSP, achieved comparable outcomes despite less follow-up treatment. Observation of lagged association between maternal improvement and change in child functioning should influence treatment planning for families. Clinical trial registration information-Psychotherapy for Depressed

  19. Resisting chocolate temptation using a brief mindfulness strategy.

    Science.gov (United States)

    Jenkins, Kim T; Tapper, Katy

    2014-09-01

    We examined the effects of two mindfulness-based strategies on chocolate consumption amongst individuals who were trying to reduce the amount of chocolate they consumed. Participants (n = 137) were allocated to one of three conditions and employed either cognitive defusion, acceptance, or relaxation (control) techniques to help them resist chocolate over 5 days. During this period, they carried a bag of chocolates with them and recorded any chocolate or chocolate-related products they consumed. They also completed a questionnaire measure of the extent to which chocolate consumption was automatic, both before and after the 5-day period. Results showed that compared to controls, those in the cognitive defusion group ate significantly less chocolate from the bag (p = .046) and less chocolate according to the diary measure (p = .053). There was evidence that these changes were brought about by reductions in the extent to which chocolate consumption was automatic. There were no differences in chocolate consumption between the acceptance and control groups. Our results point to a promising brief intervention strategy and highlight the importance of disentangling the effects of different mindfulness-based techniques. What is already known on this subject? Multicomponent mindfulness interventions have been successfully applied to a range of health behaviours. Low levels of self-control are associated with weight gain and a higher BMI. What does this study add? The results show that a brief mindfulness strategy (defusion) helps individuals resist chocolate over 5 days. The results suggest this may be brought about by reductions in the extent to which eating chocolate is automatic. A second brief mindfulness strategy (acceptance) failed to help individuals resist chocolate. © 2013 The British Psychological Society.

  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. New approach to technology advocated at House briefing

    Science.gov (United States)

    White, Catherine

    At a House Committee on Science, Space and Technology briefing on July 26, witnesses from the Institute for Policy Studies testified in support of a new approach to technology emphasizing science and technology for the public good and focusing on small, widely distributed projects.The testimony was based on the institute's recently published book, Technology for the Common Good, which concludes that in the wake of the Cold War era, technology policy should advance the broad public good over the narrow interests of a few businesses and budget-hungry agencies. The book echoes a report released by the Carnegie Commission on Science, Technology, and Government several weeks ago.

  2. Brief-stimulus presentations on multiform tandem schedules

    OpenAIRE

    Reed, Phil

    1994-01-01

    Three experiments examined the influence of a brief stimulus (a light) on the behavior of food-deprived rats whose lever pressing on tandem schedules comprising components of different schedule types resulted in food presentation. In Experiment 1, either a tandem variable-ratio variable-interval or a tandem variable-interval variable-ratio schedule was used. The variable-interval requirement in the tandem variable-ratio variable-interval schedule was yoked to the time taken to complete the va...

  3. Redefining Outcome Measurement: A Model for Brief Psychotherapy.

    Science.gov (United States)

    McGuinty, Everett; Nelson, John; Carlson, Alain; Crowther, Eric; Bednar, Dina; Foroughe, Mirisse

    2016-05-01

    The zeitgeist for short-term psychotherapy efficacy has fundamentally shifted away from evidence-based practices to include evidence-informed practices, resulting in an equally important paradigm shift in outcome measurement designed to reflect change in this short-term modality. The present article delineates a short-term psychotherapy structure which defines four fundamental stages that all brief therapies may have in common, and are represented through Cognitive Behavioral Therapy, Solution-Focused Brief Therapy, Narrative Therapy, and Emotion-Focused Therapy. These four theoretical approaches were analyzed via a selected literature review through comparing and contrasting specific and common tasks as they relate to the process of psychotherapy and change. Once commonalities were identified within session, they were categorized or grouped into themes or general stages of change within the parameters of a four to six session model of short-term therapy. Commonalities in therapeutic stages of change may more accurately and uniformly measure outcome in short-term work, unlike the symptom-specific psychometric instruments of longer-term psychotherapy. A systematic framework for evaluating the client and clinician adherence to 20 specific tasks for these four short-term therapies is presented through the newly proposed, Brief Task Acquisition Scale (BTAS). It is further proposed that the client-clinicians' adherence to these tasks will track and ultimately increase treatment integrity. Thus, when the client-clinician relationship tracks and evaluates the three pillars of (1) stage/process change, (2) task acquisition, and (3) treatment integrity, the culmination of these efforts presents a new way of more sensitively measuring outcome in short-term psychotherapy. Data collection is suggested as a first step to empirically evaluate the testable hypotheses suggested within this current model. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message The

  4. Brief review: sleep health and safety for transportation workers

    Directory of Open Access Journals (Sweden)

    Quan SF

    2015-03-01

    Full Text Available Accidents related to sleepiness related fatigue are an important concern in transportation related industries. This brief review outlines the public safety concerns with sleepiness related fatigue in the railroad, aviation and motor vehicle transportation fields. In addition, the common causes of sleepiness related fatigue, and impact on operators and their families are highlighted. It is suggested that in addition to greater recognition and changes in duty hour regulations, there should be a greater emphasis on the education of operators on the importance of sleep and circadian factors in causing fatigue, as well as strategies to mitigate their impact.

  5. The history of Croatian Trauma Society - a brief overview.

    Science.gov (United States)

    Bakota, B; Vlahovic, T; Staresinic, M; Dobric, I; Civaric, T

    2013-09-01

    Croatian Trauma Society (CTS) has a 51 year of history and tradition. This article represents a brief overview from the times when it was founded, June 30, 1961, until the present time. It tells us about the idea how, where and when the "Section for Traumatology" was founded, its activities and influence not only to promote patient trauma care but initiation of other societies dealing with traumatized patients as well, including the evolution of the CTS itself. The authors thank to all the contributors that made this article possible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. SOLUTION FOCUSED BRIEF COUNSELING (SFBC: ALTERNATIF PENDEKATAN DALAM KONSELING KELUARGA

    Directory of Open Access Journals (Sweden)

    Sumarwiyah -

    2015-11-01

    Full Text Available Solution Focused Brief Counseling meruppakan pendekatan konseling yang didasari oleh suatu pandangan bahwa sejatinya kebenaran dan realitas bukanlah suatu yang bersifat absolute namun realitas dan kebenaran itu dapat dikonstruksikan. Dalam konteks konseling keluarga dominasi salah satu anggota dana tau kepala keluarga sering menjadi pemicu masalah sehingga perlu didudukkan pada satu konteks penyelesaian masalah berbasis pada realitas yang ada. Konsleing keluarga dengan pendekatan ini memungkinkan konseli yang bermasalah dalam konteks keluarga memperoleh kemandirian dalam menyelesaikan masalah dan mencari solusi secara cepat dan tepat dalam mengatasi masalah-maslah yang ada dalam keluarga. Normal 0 false false false EN-US X-NONE X-NONE

  7. Brief to the Cluff Lake Board of Inquiry

    International Nuclear Information System (INIS)

    1977-04-01

    The purpose of this brief is to describe the structure and operations of the Atomic Energy Control Board, and to indicate how these relate to current activities and to possible future developments with respect to the nuclear fuel cycle. The problem areas from the regulatory viewpoint may be identified as follows: protection of the health of workers and the public; protection of the environment; the safe use of nuclear materials, equipment and technology for peaceful and lawful purposes. The attention of regulatory authorities has been focused on all these areas, perhaps without much public awareness, but today the increasing public concern necessitates a parallel increase in public information and participation

  8. Long-Term Effectiveness of a Brief Restorative Justice Intervention.

    Science.gov (United States)

    Kennedy, Joseph L D; Tuliao, Antover P; Flower, KayLee N; Tibbs, Jessie J; McChargue, Dennis E

    2018-06-01

    This research investigated the effectiveness of a brief Restorative Justice Intervention. Probationers who attended a Restorative Justice Intervention ( n = 383) were compared with probationers receiving treatment as usual ( n = 130) over a 2- to 6-year follow-up period. The proportion of individuals who recidivated in the control condition ( n = 89, 68.46%) were higher compared with those who recidivated in the intervention condition ( n = 127, 33.16%; z = 7.04, p restorative justice. Implications of these effects are discussed.

  9. A Brief Introduction to Astronomy in the Middle East

    CERN Document Server

    Steele, John M

    2012-01-01

    The Middle East is the birthplace of astronomy and the centre for its development during the medieval period. In this brief introduction John Steele offers an intriguing insight into Middle Eastern achievements in astronomy and their profound influence on the rest of the world. Amongst other things, the book traces the Late Babylonians' ingenious schemes for modelling planetary motion. It also reveals how medieval Islamic advances in the study of the heavens, and the design of precise astronomical instruments, led to breakthroughs by Renaissance practitioners such as Copernicus and Kepler. An

  10. Factor structure of the Brief Negative Symptom Scale.

    Science.gov (United States)

    Strauss, Gregory P; Hong, L Elliot; Gold, James M; Buchanan, Robert W; McMahon, Robert P; Keller, William R; Fischer, Bernard A; Catalano, Lauren T; Culbreth, Adam J; Carpenter, William T; Kirkpatrick, Brian

    2012-12-01

    The current study examined the factor structure of the Brief Negative Symptom Scale (BNSS), a next-generation negative symptom rating instrument developed in response to the NIMH-sponsored Consensus Development Conference on Negative Symptoms. Participants included 146 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Principal axis factoring indicated two distinct factors explaining 68.7% of the variance. Similar to previous findings, the factors reflected motivation and pleasure and emotional expressivity. These findings provide further support for the construct validity of the BNSS, and for the existence of these two negative symptom factors. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. ROMANIAN AERONAUTICAL METEOROLOGY APPLICABLE LEGAL FRAMEWORK –BRIEFING

    Directory of Open Access Journals (Sweden)

    CATALIN POPA

    2012-05-01

    Full Text Available The purpose of this briefing is toprovide an overview of the aeronautical meteorology legal framework in Romania. In this context, the role and importance of aeronautical meteorology in international air traffic management will be underlined, with focus on the civil aviation activity in Romania. The international legal framework and modalities of implementing these rules at national level will constitute a significant part of the present study., Specific accent will be put on the national regulatory framework and structure, means of updating it, and how it responds to changing regulatory requirements.

  12. Xeroderma Pigmentosum: A Bane in developing country – Brief report

    Directory of Open Access Journals (Sweden)

    Hari Kishan Kumar Yadalla

    2014-10-01

    Full Text Available Xeroderma pigmentosum (XP is a rare autosomal recessive disorder characterized by photosensitivity, cutaneous pigmentary changes, premature skin ageing, and the development of various cutaneous and internal malignancies at an early age. We present this case of a 10 year-old girl in a developing country like India, with significant corneal scarring and multiple cutaneous skin lesions in sun-exposed areas. Developmental delay had been present since 3 months of age, with these clinical features it was consistent with Xeroderma Pigmentosum. We highlight the difficulties encountered due to the lack of diagnostic and treatment modalities for this child, and offer a brief review of XP, including emerging treatments.

  13. Treatment modalities for hyperpigmented skin lesions: A brief overview

    Directory of Open Access Journals (Sweden)

    Yan Teng Khoo

    2016-07-01

    Full Text Available Skin hyperpigmentation involves a broad range of skin conditions, including epidermal pigmented lesions, dermal pigmented lesions, and mixed pigmented lesions. Treatment includes various modalities such as brightening cream, chemical peeling, and laser therapy. Responses to various treatment modalities can be quite varied depending on the type of treatment and the degree of pigmentation. Sometimes a lesion can lighten or even partially disappear, while other lesions may recur. This paper provides a brief overview of treatment modalities available for hyperpigmented skin lesions including the importance of photoprotection, various types of brightening creams, suitable types of chemical peels, specific laser therapies targeted for skin hyperpigmentation, and surgery.

  14. 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.

  15. My brief history. 2. ed.; Meine kurze Geschichte

    Energy Technology Data Exchange (ETDEWEB)

    Hawking, Stephen

    2015-11-01

    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.

  16. Compton camera imaging and the cone transform: a brief overview

    Science.gov (United States)

    Terzioglu, Fatma; Kuchment, Peter; Kunyansky, Leonid

    2018-05-01

    While most of Radon transform applications to imaging involve integrations over smooth sub-manifolds of the ambient space, lately important situations have appeared where the integration surfaces are conical. Three of such applications are single scatter optical tomography, Compton camera medical imaging, and homeland security. In spite of the similar surfaces of integration, the data and the inverse problems associated with these modalities differ significantly. In this article, we present a brief overview of the mathematics arising in Compton camera imaging. In particular, the emphasis is made on the overdetermined data and flexible geometry of the detectors. For the detailed results, as well as other approaches (e.g. smaller-dimensional data or restricted geometry of detectors) the reader is directed to the relevant publications. Only a brief description and some references are provided for the single scatter optical tomography. This work was supported in part by NSF DMS grants 1211463 (the first two authors), 1211521 and 141877 (the third author), as well as a College of Science of Texas A&M University grant.

  17. Development of a brief version of the Pathological Narcissism Inventory.

    Science.gov (United States)

    Schoenleber, Michelle; Roche, Michael J; Wetzel, Eunike; Pincus, Aaron L; Roberts, Brent W

    2015-12-01

    With theoretical and empirical interest in narcissism growing, there is a need for brief measures of pathological narcissism that can be used more practically while assessing the construct comprehensively. Data from four samples (total N = 3,851) collected across two separate research groups and representing undergraduate, community, and clinical populations were used to establish the reliability, validity, and utility of the Brief-Pathological Narcissism Inventory (B-PNI). Item response theory and confirmatory factor analyses were used to determine the best-performing 28 items from the original PNI and ensure that the B-PNI exhibited a factor structure consistent with the original PNI. Items were retained for all seven pathological narcissism facet scales. Additional results also support the criterion validity of the B-PNI, suggesting that it can be used in place of the original PNI to assess the various facets of pathological narcissism effectively and without loss of information, which may enhance the ability of researchers to investigate pathological narcissism in future work. (c) 2015 APA, all rights reserved).

  18. A brief symptom index for advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cella David

    2006-09-01

    Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

  19. A departmental brief to the Ontario Nuclear Safety Review

    International Nuclear Information System (INIS)

    1987-09-01

    The major nuclear activity in Canada is that associated with the generation of electricity by nuclear power stations. This area is in part subject to federal jurisdiction under the authority of the Atomic Energy Control Board. Environment Canada can play a significant role in influencing decisions regarding environmental aspects of nuclear energy development. The Department believes that the best way to preserve the quality of the environment is to anticipate and prevent problems before they arise. However, even if all precautionary measures were taken in the design and operating procedures of nuclear power stations, accidents can occur and radionuclides and toxic pollutants may escape and disperse into the environment. This brief outlines the rationale for Environment Canada's involvement and role in the nuclear area, and the major programs and activities of the Department with respect to environmental protection and emergency preparedness. The brief also makes recommendations for consideration of environmental protection technologies for nuclear power stations, for improved measurement and modelling capabilities relating to release and dispersion of radionuclides during accident conditions, and for improved communication with the public following a nuclear emergency. Environment Canada recommends that an appropriate environmental review process be undertaken for new or expanded nuclear facilities in Ontario

  20. Brief histories of medical physics in Asia-Oceania.

    Science.gov (United States)

    Round, W H; Jafari, S; Kron, T; Azhari, H A; Chhom, S; Hu, Y; Mauldon, G F; Cheung, K Y; Kuppusamy, T; Pawiro, S A; Lubis, L E; Soejoko, D S; Haryanto, F; Endo, M; Han, Y; Suh, T S; Ng, K H; Luvsan-Ish, A; Maung, S O; Chaurasia, P P; Jafri, S M A; Farrukh, S; Peralta, A; Toh, H J; Sarasanandarajah, S; Shiau, A C; Krisanachinda, A; Suriyapee, S; Vinijsorn, S; Nguyen, T C

    2015-09-01

    The history of medical physics in Asia-Oceania goes back to the late nineteenth century when X-ray imaging was introduced, although medical physicists were not appointed until much later. Medical physics developed very quickly in some countries, but in others the socio-economic situation as such prevented it being established for many years. In others, the political situation and war has impeded its development. In many countries their medical physics history has not been well recorded and there is a danger that it will be lost to future generations. In this paper, brief histories of the development of medical physics in most countries in Asia-Oceania are presented by a large number of authors to serve as a record. The histories are necessarily brief; otherwise the paper would quickly turn into a book of hundreds of pages. The emphasis in each history as recorded here varies as the focus and culture of the countries as well as the length of their histories varies considerably.

  1. [Psychometric assessment of a brief Modern Racism Scale].

    Science.gov (United States)

    Campo-Arias, Adalberto; Herazo, Edwin; Oviedo, Heidi C

    2016-06-01

    Objective To find the internal consistency of the Modern Racism Scale (MRS) among medical students in Bucaramanga, Colombia. Methods A total of 352 medical students, mean age=20.0 years (SD=1.9) reported their attitudes towards Afro-Colombians; 59.4 % were women. Students completed the 10-item version of MRS. Cronbach alpha and McDonald omega were calculated. Exploratory factor analyses were done to propose a brief version of the MRS. Results The 10-item version showed a Cronbach alpha of 0.48 and a McDonald omega of 0.15. The short version, the Brief Modern Racism Scale (BMRS) (items 1, 4, 5, 7 and 8) presented a Cronbach alpha of 0.64 and McDonald omega of 0.65. The BMRS showed one salient factor responsible of 41.6 % of the total variance. Conclusions A Spanish-language short version of the MRS shows better psychometric performance than the original version. Further study is needed to corroborate these findings or make adjustments for Colombian cultural regions.

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. 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.

  7. Quarterly Briefing Book on Environmental and Waste Management Activities

    International Nuclear Information System (INIS)

    Brown, M.C.

    1991-06-01

    The purpose of the Quarterly Briefing Book on Environmental and Waste Management Activities is to provide managers and senior staff at the US Department of Energy-Richland Operations Office and its contractors with timely and concise information on Hanford Site environmental and waste management activities. Each edition updates the information on the topics in the previous edition, deletes those determined not to be of current interest, and adds new topics to keep up to date with changing environmental and waste management requirements and issues. Section A covers current waste management and environmental restoration issues. In Section B are writeups on national or site-wide environmental and waste management topics. Section C has writeups on program- and waste-specific environmental and waste management topics. Section D provides information on waste sites and inventories on the site. 15 figs., 4 tabs

  8. A BRIEF SOCIO-LINGUISTIC SURVEY OF ZHOUQU TIBETAN

    Directory of Open Access Journals (Sweden)

    Abe Powell

    2018-05-01

    Full Text Available This paper presents a brief sketch of the socio-linguistic situation of Zhouqu Tibetan, a unique Tibetic variety spoken in Gansu Province, China. The authors used participatory methods to investigate questions of language vitality, domains of language use, language attitudes, and dialectal variation. The results show that: (1 Zhouqu Tibetan is used in all language domains; (2 locals see their language as an integral part of their identity even though they acknowledge that Chinese language proficiency is necessary for employment, education, and healthcare; and (3 locals perceive little in the way of dialectal variation in Zhouqu Tibetan, with only Boyu Village's speech variety being divergent to the point that it impacts intelligibility.

  9. Center for modeling of turbulence and transition: Research briefs, 1995

    Science.gov (United States)

    1995-10-01

    This research brief contains the progress reports of the research staff of the Center for Modeling of Turbulence and Transition (CMOTT) from July 1993 to July 1995. It also constitutes a progress report to the Institute of Computational Mechanics in Propulsion located at the Ohio Aerospace Institute and the Lewis Research Center. CMOTT has been in existence for about four years. In the first three years, its main activities were to develop and validate turbulence and combustion models for propulsion systems, in an effort to remove the deficiencies of existing models. Three workshops on computational turbulence modeling were held at LeRC (1991, 1993, 1994). At present, CMOTT is integrating the CMOTT developed/improved models into CFD tools which can be used by the propulsion systems community. This activity has resulted in an increased collaboration with the Lewis CFD researchers.

  10. A Brief Overview of the Civil Union Act

    Directory of Open Access Journals (Sweden)

    N Ntlama

    2010-05-01

    Full Text Available The adoption of the Constitution of the Republic of South Africa, 1996 (the Constitution has provided a sound framework for the elimination of discrimination and prejudice against all members of our society. The Constitution provides for equal recognition of the right to freedom of religion and sexual orientation within the framework of the right to equality. This note aims to provide a brief overview and analysis of the general and potentially problematic features of the Civil Union Act 17 of 2006 (the Act in the context of equality, generally and within realm of the constitutional protection afforded to everyone in South Africa. This contribution is limited to an examination of the quality of the legal protection accorded to same-sex couples as envisaged inthe Act, and not to an analysis of the nature of the institution of marriage itself or the theological and social dimensions of same-sex marriages.

  11. History of orthopaedics in China: a brief review.

    Science.gov (United States)

    Li, Jia; Zhang, Yingze

    2018-03-01

    Chinese orthopaedic surgeons have made a substantial contribution to the development of orthopaedics worldwide, and traditional Chinese medicine (TCM) in orthopaedics has a very long history in China. We make a brief review of the development of orthopaedics in China, intending to pave the way for further understanding of Chinese orthopaedics for scholars all over the world. The description of fractures firstly appeared in 3600 years ago in China, and the theories, experience, and treatment strategies of TCM still play important roles in clinical diagnosis and treatment of orthopaedic disorders in our country. Western orthopaedics was first introduced into China in the early twentieth century. After decades of development, Chinese scholars have made some gratifying achievements in orthopaedics. Orthopaedics is constantly evolving, and we need to strengthen the ability of independent innovation to achieve orthopaedic surgeons' Chinese dream, and better serve our patients.

  12. Ozone therapy in dentistry. A brief review for physicians.

    Science.gov (United States)

    Domb, William C

    2014-10-31

    The 21(st) century dental practice is quite dynamic. New treatment protocols and new materials are being developed at a rapid pace. Ozone dental therapy falls into the category of new treatment protocols in dentistry, yet ozone is not new at all. Ozone therapy is already a major treatment modality in Europe, South America and a number of other countries. What is provided here will not be an exhaustive scientific treatise so much as a brief general introduction into what dentists are now doing with ozone therapies and the numerous oral/systemic links that make this subject so important for physicians so that, ultimately, they may serve their patients more effectively and productively.

  13. Energy predictions. [Briefs on 33 charts, figures, and graphs

    Energy Technology Data Exchange (ETDEWEB)

    Freiwald, D.A.

    1977-01-01

    Briefs describe 33 charts, graphs, and schematics offering some recent history and perspectives on the world and U.S. energy situation and the problems for survival facing the world. Of interest is Figure 28, showing the Club of Rome's model of the earth in terms of resource consumption, food, money, people, pollution, etc. A computer was asked to extend recent history into the future and results indicate a collapse of the industrialized system towards an agrarian culture around the year 2025. It is noted that the model did not consider technological initiative or man's willingness to change lifestyles. The final (33) schematic is a guesstimate of noticeable impact timescales, indicating when research projects on transition or ultimate energy sources at LASL might be expected to yield impact. (MCW)

  14. National briefing summaries: Nuclear fuel cycle and waste management

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, K.J.; Lakey, L.T.; Silviera, D.J.

    1988-12-01

    The National Briefing Summaries is a compilation of publicly available information concerning the nuclear fuel cycle and radioactive waste management strategies and programs of 21 nations, including the United States and three international agencies that have publicized their activities in this field. It presents available highlight information with references that may be used by the reader for additional information. The information in this document is compiled primarily for use by the US Department of Energy and other US federal agencies and their contractors to provide summary information on radioactive waste management activities in other countries. This document provides an awareness to managers and technical staff of what is occurring in other countries with regard to strategies, activities, and facilities. The information may be useful in program planning to improve and benefit United States' programs through foreign information exchange. Benefits to foreign exchange may be derived through a number of exchange activities.

  15. National briefing summaries: Nuclear fuel cycle and waste management

    International Nuclear Information System (INIS)

    Schneider, K.J.; Bradley, D.J.; Fletcher, J.F.; Konzek, G.J.; Lakey, L.T.; Mitchell, S.J.; Molton, P.M.; Nightingale, R.E.

    1991-04-01

    Since 1976, the International Program Support Office (IPSO) at the Pacific Northwest Laboratory (PNL) has collected and compiled publicly available information concerning foreign and international radioactive waste management programs. This National Briefing Summaries is a printout of an electronic database that has been compiled and is maintained by the IPSO staff. The database contains current information concerning the radioactive waste management programs (with supporting information on nuclear power and the nuclear fuel cycle) of most of the nations (except eastern European countries) that now have or are contemplating nuclear power, and of the multinational agencies that are active in radioactive waste management. Information in this document is included for three additional countries (China, Mexico, and USSR) compared to the prior issue. The database and this document were developed in response to needs of the US Department of Energy

  16. A brief description of Polanco`s hybrid system

    Energy Technology Data Exchange (ETDEWEB)

    Nunes, Ventura [Instituto de Ingenieria Electrica, Universidad de la Republica, Montevideo (Uruguay)

    1997-12-31

    Since 1995, a hybrid system wind - PV is in service in Polanco, Uruguay. A brief description of this system and the criteria employed in its design are outlined. The experience obtained during two years operation are described from the points of view of the equipment reliability and of the electrical service provided. Future prospects of this kind of installations in Uruguay as part of the rural electrification policy are presented. [Espanol] Desde 1995 esta en servicio en Polanco, Uruguay un sistema hibrido viento-fotovoltaico. Aqui se describe brevemente este sistema y el criterio empleado en su diseno. Se describe la experiencia obtenida durante dos anos de operacion desde el punto de vista de confiabilidad de los equipos y del servicio electrico proporcionado. Se presentan prospectos futuros de esta clase de instalaciones en Uruguay, como parte de la politica de electrificacion rural.

  17. Quarterly Briefing Book on Environmental and Waste Management Activities

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.C.

    1991-06-01

    The purpose of the Quarterly Briefing Book on Environmental and Waste Management Activities is to provide managers and senior staff at the US Department of Energy-Richland Operations Office and its contractors with timely and concise information on Hanford Site environmental and waste management activities. Each edition updates the information on the topics in the previous edition, deletes those determined not to be of current interest, and adds new topics to keep up to date with changing environmental and waste management requirements and issues. Section A covers current waste management and environmental restoration issues. In Section B are writeups on national or site-wide environmental and waste management topics. Section C has writeups on program- and waste-specific environmental and waste management topics. Section D provides information on waste sites and inventories on the site. 15 figs., 4 tabs.

  18. National briefing summaries: Nuclear fuel cycle and waste management

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, K.J.; Bradley, D.J.; Fletcher, J.F.; Konzek, G.J.; Lakey, L.T.; Mitchell, S.J.; Molton, P.M.; Nightingale, R.E.

    1991-04-01

    Since 1976, the International Program Support Office (IPSO) at the Pacific Northwest Laboratory (PNL) has collected and compiled publicly available information concerning foreign and international radioactive waste management programs. This National Briefing Summaries is a printout of an electronic database that has been compiled and is maintained by the IPSO staff. The database contains current information concerning the radioactive waste management programs (with supporting information on nuclear power and the nuclear fuel cycle) of most of the nations (except eastern European countries) that now have or are contemplating nuclear power, and of the multinational agencies that are active in radioactive waste management. Information in this document is included for three additional countries (China, Mexico, and USSR) compared to the prior issue. The database and this document were developed in response to needs of the US Department of Energy.

  19. Theoretical development of information science: A brief history

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    the strongest “paradigms” in the field is a tradition derived from the Cranfield experiments in the 1960s and the bibliometric research following the publication of Science Citation Index from 1963 and forward. Among the competing theoretical frameworks, ‘the cognitive view’ became influential from the 1970s......This paper presents a brief history of information science (IS) as viewed by the author. The term ‘information science’ goes back to 1955 and evolved in the aftermath of Claude Shannon’s ‘information theory’ (1948), which also inspired research into problems in fields of library science...... and documentation. These subjects were a main focus of what became established as ‘information science’, which from 1964 onwards was often termed ‘library and information science’ (LIS). However, the usefulness of Shannon’s information theory as the theoretical foundation of the field was been challenged. Among...

  20. National briefing summaries: Nuclear fuel cycle and waste management

    International Nuclear Information System (INIS)

    Schneider, K.J.; Lakey, L.T.; Silviera, D.J.

    1988-12-01

    The National Briefing Summaries is a compilation of publicly available information concerning the nuclear fuel cycle and radioactive waste management strategies and programs of 21 nations, including the United States and three international agencies that have publicized their activities in this field. It presents available highlight information with references that may be used by the reader for additional information. The information in this document is compiled primarily for use by the US Department of Energy and other US federal agencies and their contractors to provide summary information on radioactive waste management activities in other countries. This document provides an awareness to managers and technical staff of what is occurring in other countries with regard to strategies, activities, and facilities. The information may be useful in program planning to improve and benefit United States' programs through foreign information exchange. Benefits to foreign exchange may be derived through a number of exchange activities