Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02

PubMed Central

Lee, Eudocia Q.; Kuhn, John; Lamborn, Kathleen R.; Abrey, Lauren; DeAngelis, Lisa M.; Lieberman, Frank; Robins, H. Ian; Chang, Susan M.; Yung, W. K. Alfred; Drappatz, Jan; Mehta, Minesh P.; Levin, Victor A.; Aldape, Kenneth; Dancey, Janet E.; Wright, John J.; Prados, Michael D.; Cloughesy, Timothy F.; Gilbert, Mark R.; Wen, Patrick Y.

2012-01-01

The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor–β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents. PMID:23099651

Death from undiagnosed glioblastoma multiforme and toxic self-medication presenting with concurrent dysfunctional behavior.

PubMed

Carson, Henry J; Eilers, Stanley G

2008-08-01

We encountered a decedent with an unexpected glioblastoma multiforme. A 61-year-old retired African-American woman was found dead in her home, fully clothed in her bathtub, with a pillow under her head. At autopsy, the brain showed a glioblastoma multiforme. Toxicology showed elevated hydrocodone, propoxyphene, acetaminophen, and positive paroxetine. The presence of a brain tumor likely caused a severe headache. The use of her medications could have indicated a reaction to the escalating pain of the brain trauma, and overuse could be consistent with escalating pain or loss of rational thought processes. The present case is interesting in that it had evidence of behavioral dysfunction that could be related to the brain tumor, and death arising from the glioblastoma multiforme (cerebral hemorrhage and edema) with concurrent multiple drug intoxication.

[A new case of Rowell's syndrome].

PubMed

Schissler, C; Banea, S; Tortel, M-C; Mahé, A

2017-04-01

This article introduces a new case of Rowell's syndrome, a controversial entity defined by the association of lupus erythematosus and erythema multiforme. A 43-year-old woman was diagnosed with lupus erythematosus induced by esomeprazole. Because her eruption did not improve after withdrawal of the drug, hydroxychloroquine was administered. Two weeks later, the patient described new annular lesions on her chest and arms, both erosive and crusted, and some had a target-like appearance. The oral mucosa was also affected. Histology revealed sub-epidermal blistering with keratinocytic necrosis, strongly suggesting erythema multiforme. Screening for other causes of erythema multiforme proved negative. A positive outcome was achieved with corticosteroids and hydroxychloroquine. One year later, the patient was in complete remission for both lupus erythematosus and erythema multiforme. The association of lupus erythematosus and erythema multiforme first described in 1963 is known as Rowell's syndrome. While diagnostic criteria have been established in the literature, the reality of this entity is still contested. The annular lesions of subacute lupus erythematosus may be confused with the lesions of erythema multiforme. As suggested in the above section, other authors consider Rowell's syndrome to be a singular entity. Indeed, our patient developed lesions distinct from those initially suggesting subacute lupus erythematosus, in particular: the target-like aspect of the elementary lesions, mucosal involvement, a distinct histological aspect, and dissociated outcomes. Ultimately, the definition of Rowell's syndrome remains highly debated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tonsillary carcinoma after temozolomide treatment for glioblastoma multiforme: treatment-related or dual-pathology?

PubMed

Binello, E; Germano, I M

2009-08-01

Glioblastoma multiforme is a primary malignant brain tumor with a prognosis of typically less than 2 years. Standard treatment paradigms include surgery, radiation therapy and temozolomide. Little data exists for temozolomide recommendations after the first 6 months. We present a case of a patient with glioblastoma multiforme treated with surgery, radiation and chronic temozolomide for 6 years. He continues to survive glioblastoma-recurrence-free, but developed tonsillary carcinoma. This case raises the question of whether this secondary solid-organ malignancy is treatment-related or dual pathology.

Exploratory analysis of the copy number alterations in glioblastoma multiforme.

PubMed

Freire, Pablo; Vilela, Marco; Deus, Helena; Kim, Yong-Wan; Koul, Dimpy; Colman, Howard; Aldape, Kenneth D; Bogler, Oliver; Yung, W K Alfred; Coombes, Kevin; Mills, Gordon B; Vasconcelos, Ana T; Almeida, Jonas S

2008-01-01

The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise. Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome) and (http://bioinformaticstation.org), respectively. The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility.

PubMed

Walter, S D; Han, H; Briel, M; Guyatt, G H

2017-04-30

In this paper, we consider the potential bias in the estimated treatment effect obtained from clinical trials, the protocols of which include the possibility of interim analyses and an early termination of the study for reasons of futility. In particular, by considering the conditional power at an interim analysis, we derive analytic expressions for various parameters of interest: (i) the underestimation or overestimation of the treatment effect in studies that stop for futility; (ii) the impact of the interim analyses on the estimation of treatment effect in studies that are completed, i.e. that do not stop for futility; (iii) the overall estimation bias in the estimated treatment effect in a single study with such a stopping rule; and (iv) the probability of stopping at an interim analysis. We evaluate these general expressions numerically for typical trial scenarios. Results show that the parameters of interest depend on a number of factors, including the true underlying treatment effect, the difference that the trial is designed to detect, the study power, the number of planned interim analyses and what assumption is made about future data to be observed after an interim analysis. Because the probability of stopping early is small for many practical situations, the overall bias is often small, but a more serious issue is the potential for substantial underestimation of the treatment effect in studies that actually stop for futility. We also consider these ideas using data from an illustrative trial that did stop for futility at an interim analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

Cancer.gov

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.

mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma.

PubMed

Bache, Matthias; Rot, Swetlana; Keßler, Jacqueline; Güttler, Antje; Wichmann, Henri; Greither, Thomas; Wach, Sven; Taubert, Helge; Söling, Ariane; Bilkenroth, Udo; Kappler, Matthias; Vordermark, Dirk

2015-06-01

The roles of hypoxia-induced and stem cell-associated genes in the development of malignancy and tumour progression are well known. However, there are a limited number of studies analysing the impact of mRNA expression levels of hypoxia-induced and stem cell-associated genes in the tissues of brain tumours and glioblastoma patients. In this study, tumour tissues from patients with glioblastoma multiforme and tumour adjacent tissues were analysed. We investigated mRNA expression levels of hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), carbonic anhydrase 9 (CA9), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and osteopontin (OPN), and stem cell-associated genes survivin, epidermal growth factor receptor (EGFR), human telomerase reverse transcriptase (hTERT), Nanog and octamer binding transcription factor 4 (OCT4) using quantitative real-time polymerase chain reaction (qRT-PCR). Our data revealed higher mRNA expression levels of hypoxia-induced and stem cell-associated genes in tumour tissue than levels in the tumour adjacent tissues in patients with glioblastoma multiforme. A strong positive correlation between the mRNA expression levels of HIF-2α, CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA expression in glioblastoma multiforme. Additionally, the results indicate the role of stem-cell-related genes in tumour hypoxia. Kaplan-Maier analysis revealed that high mRNA expression levels of hypoxia-induced markers showed a trend towards shorter overall survival in glioblastoma patients (P=0.061). Our data suggest that mRNA expression levels of hypoxia-induced genes are important tumour markers in patients with glioblastoma multiforme.

Temozolomide and other potential agents for the treatment of glioblastoma multiforme.

PubMed

Nagasawa, Daniel T; Chow, Frances; Yew, Andrew; Kim, Won; Cremer, Nicole; Yang, Isaac

2012-04-01

This article provides historical and recent perspectives related to the use of temozolomide for the treatment of glioblastoma multiforme. Temozolomide has quickly become part of the standard of care for the modern treatment of stage IV glioblastoma multiforme since its approval in 2005. Yet despite its improvements from previous therapies, median survival remains approximately 15 months, with a 2-year survival rate of 8% to 26%. The mechanism of action of this chemotherapeutic agent, conferred advantages and limitations, treatment resistance and rescue, and potential targets of future research are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

PubMed Central

Korbecki, Jan; Gutowska, Izabela; Kojder, Ireneusz; Jeżewski, Dariusz; Goschorska, Marta; Łukomska, Agnieszka; Lubkowska, Anna; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

2018-01-01

Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the ‘hallmarks of cancer’ in glioblastoma multiforme. Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme. PMID:29467963

Prognostic significance of IDH 1 mutation in patients with glioblastoma multiforme.

PubMed

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-05-01

Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1. A systematic review reported similar results. Based on the review of current literature IDH1 mutation is an independent factor for longer overall survival (OS) and progression free survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic significance opens up new avenues for treatment.

78 FR 20503 - Energy Conservation Program: Availability of the Interim Technical Support Document for High...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... Conservation Program: Availability of the Interim Technical Support Document for High-Intensity Discharge Lamps... high-intensity discharge (HID) lamps energy conservation standards in the Federal Register. This... interim analysis for high- intensity discharge lamps energy conservation standards. The notice provided...

Evaluation and analysis of Seasat-A scanning multichannel Microwave Radiometer (SMMR) Antenna Pattern Correction (APC) algorithm

NASA Technical Reports Server (NTRS)

Kitzis, J. L.; Kitzis, S. N.

1979-01-01

The brightness temperature data produced by the SMMR final Antenna Pattern Correction (APC) algorithm is discussed. The algorithm consisted of: (1) a direct comparison of the outputs of the final and interim APC algorithms; and (2) an analysis of a possible relationship between observed cross track gradients in the interim brightness temperatures and the asymmetry in the antenna temperature data. Results indicate a bias between the brightness temperature produced by the final and interim APC algorithm.

Multiple emulsions as effective platforms for controlled anti-cancer drug delivery.

PubMed

Dluska, Ewa; Markowska-Radomska, Agnieszka; Metera, Agata; Tudek, Barbara; Kosicki, Konrad

2017-09-01

Developing pH-responsive multiple emulsion platforms for effective glioblastoma multiforme therapy with reduced toxicity, a drug release study and modeling. Cancer cell line: U87 MG, multiple emulsions with pH-responsive biopolymer and encapsulated doxorubicin (DOX); preparation of multiple emulsions in a Couette-Taylor flow biocontactor, in vitro release study of DOX (fluorescence intensity analysis), in vitro cytotoxicity study (alamarBlue cell viability assay) and numerical simulation of DOX release rates. The multiple emulsions offered a high DOX encapsulation efficiency (97.4 ± 1%) and pH modulated release rates of a drug. Multiple emulsions with a low concentration of DOX (0.02 μM) exhibited broadly advanced cell (U87 MG) cytotoxicity than free DOX solution used at the same concentration. Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.

Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations.

PubMed

Abernathy, Kristen; Burke, Jeremy

2016-01-01

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

75 FR 12217 - Notice of Availability for Comments Regarding the Planned Environmental Assessment Interim Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... public comments for a planned Environmental Assessment. The Corps is directed to conduct a study of.... The study is structured as a series of interim reports. Interim Report IIIa, limited to the impacts of.... Comments are requested to assist in determining the level of analysis and impacts to be considered for...

76 FR 14568 - Federal Acquisition Regulation; Use of Commercial Services Item Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

...-AL44 Federal Acquisition Regulation; Use of Commercial Services Item Authority AGENCIES: Department of... interim rule amending the Federal Acquisition Regulation (FAR) to implement section 868 of the Duncan... interim rule. II. Discussion/Analysis The analysis of public comments by the Defense Acquisition...

Interim Terrain Data (ITD) and Vector Product Interim Terrain Data (VITD) user's guide

DOT National Transportation Integrated Search

1996-09-01

This guide is intended to be a convenient reference for users of these types of terrain analysis data. ITD is a digitized version of the standard 1:50,000-scale tactical terrain analysis data base (TTADB) product produced by the Defense Mapping Agenc...

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

PubMed Central

Heiland, Dieter Henrik; Mader, Irina; Schlosser, Pascal; Pfeifer, Dietmar; Carro, Maria Stella; Lange, Thomas; Schwarzwald, Ralf; Vasilikos, Ioannis; Urbach, Horst; Weyerbrock, Astrid

2016-01-01

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS). PMID:27350391

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

PubMed

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.

Multistage Computerized Adaptive Testing with Uniform Item Exposure

ERIC Educational Resources Information Center

Edwards, Michael C.; Flora, David B.; Thissen, David

2012-01-01

This article describes a computerized adaptive test (CAT) based on the uniform item exposure multi-form structure (uMFS). The uMFS is a specialization of the multi-form structure (MFS) idea described by Armstrong, Jones, Berliner, and Pashley (1998). In an MFS CAT, the examinee first responds to a small fixed block of items. The items comprising…

Columbia University: Computational Human High-grade Glioblastoma Multiforme Interactome - miRNA (Post-transcriptional) Layer | Office of Cancer Genomics

Cancer.gov

The Human High-Grade Glioma Interactome (HGi) contains a genome-wide complement of molecular interactions that are Glioblastoma Multiforme (GBM)-specific. HGi v3 contains the post-transcriptional layer of the HGi, which includes the miRNA-target (RNA-RNA) layer of the interactome. Read the Abstract

Prognostic significance of lesion size for glioblastoma multiforme.

PubMed

Reeves, G I; Marks, J E

1979-08-01

From March 1974 to December 1976, 56 patients with glioblastoma multiforme had precraniotomy computed tomography (CT) scans from which the lesion size was determined by measuring the cross-sectional area. Thirty-two patients underwent surgery followed by irradiation, and 24 had surgery followed by irradiation and chemotherapy. There was no difference in survival between the 16 patients with small lesions and the 16 patients with large lesions in the surgery plus radiation alone group, nor in the 16 patients with small and 8 patients with large lesions in the surgery, radiation and chemotherapy group. Minimum follow-up was one year. Other possible prognostic factors including age, tumor grade, radiation dose, and performance status were comparable for each subgroup. Lesion size in glioblastoma multiforme appears unrelated to prognosis.

Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems

PubMed Central

Toren, Amos; Pismenyuk, Tatyana; Yalon, Michal; Freedman, Shani; Simon, Amos J.; Fisher, Tamar; Moshe, Itai; Reichardt, Juergen K.V.; Constantini, Shlomi; Mardor, Yael; Last, David; Guez, David; Daniels, Dianne; Assoulin, Moria; Mehrian-Shai, Ruty

2016-01-01

Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients. PMID:27556862

Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems.

PubMed

Toren, Amos; Pismenyuk, Tatyana; Yalon, Michal; Freedman, Shani; Simon, Amos J; Fisher, Tamar; Moshe, Itai; Reichardt, Juergen K V; Constantini, Shlomi; Mardor, Yael; Last, David; Guez, David; Daniels, Dianne; Assoulin, Moria; Mehrian-Shai, Ruty

2016-11-15

Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients.

Pupil Inquiry Behavior Analysis and Change Activity. Interim Project Report.

ERIC Educational Resources Information Center

Manion, Raymond C.

This interim report discusses progress toward three major goals of the Pupil Inquiry Behavior Analysis and Change Activity: increased pupil inquiry, changed teacher behavior to facilitate pupil inquiry, and the development of a 32-week course of instruction to provide for these behavioral changes. Data currently available deals with the emotional…

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications.

Diagnosis and ablation of multiform fascicular tachycardia.

PubMed

Sung, Raphael K; Kim, Albert M; Tseng, Zian H; Han, Frederick; Inada, Keiichi; Tedrow, Usha B; Viswanathan, Mohan N; Badhwar, Nitish; Varosy, Paul D; Tanel, Ronn; Olgin, Jeffrey E; Stephenson, William G; Scheinman, Melvin

2013-03-01

Fascicular tachycardia (FT) is an uncommon cause of monomorphic sustained ventricular tachycardia (VT). We describe 6 cases of FT with multiform QRS morphologies. Six of 823 consecutive VT cases were retrospectively analyzed and found attributable to FT with multiform QRS patterns, with 3 cases exhibiting narrow QRS VT as well. All underwent electrophysiology study including fascicular potential mapping, entrainment pacing, and electroanatomic mapping. The first 3 cases describe similar multiform VT patterns with successful ablation in the upper mid septum. Initially, a right bundle branch block (RBBB) VT with superior axis was induced. Radiofrequency catheter ablation (RFCA) targeting the left posterior fascicle (LPF) resulted in a second VT with RBBB inferior axis. RFCA in the upper septum just apical to the LBB potential abolished VT in all cases. Cases 4 and 5 showed RBBB VT with alternating fascicular block compatible with upper septal dependent VT, resulting in bundle branch reentrant VT (BBRT) after ablation of LPF and left anterior fascicle (LAF). Finally, Cases 5 and 6 demonstrated spontaneous shift in QRS morphology during VT, implicating participation of a third fascicle. In Case 6, successful ablation was achieved over the proximal LAF, likely representing insertion of the auxiliary fascicle near the proximal LAF. Multiform FTs show a reentrant mechanism using multiple fascicular branches. We hypothesize that retrograde conduction over the septal fascicle produces alternate fascicular patterns as well as narrow VT forms. Ablation of the respective fascicle was successful in abolishing FT but does not preclude development of BBRT unless septal fascicle is targeted and ablated. © 2012 Wiley Periodicals, Inc.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: Systematic review and meta-analysis.

PubMed

Adams, Hugo J A; Kwee, Thomas C

2016-10-01

This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interim analysis: A rational approach of decision making in clinical trial.

PubMed

Kumar, Amal; Chakraborty, Bhaswat S

2016-01-01

Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas.

PubMed

Ganeshan, B; Miles, K A; Babikir, S; Shortman, R; Afaq, A; Ardeshna, K M; Groves, A M; Kayani, I

2017-03-01

The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. • CT texture-analysis (CTTA) provides prognostic information complementary to interim FDG-PET in Lymphoma. • Pre-treatment CTTA and interim PET status were significant predictors of progression-free survival. • Patients with negative interim PET could be further stratified by pre-treatment CTTA. • Provide precision surveillance where additional imaging reserved for patients at greatest recurrence-risk. • Assists in risk-adapted treatment strategy based on interim PET and CTTA.

Gliosarcoma: A rare variant of glioblastoma multiforme in paediatric patient: Case report and review of literature

PubMed Central

Meena, Ugan Singh; Sharma, Sumit; Chopra, Sanjeev; Jain, Shashi Kant

2016-01-01

Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5th and 6th decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15 d and blurring of vision from 3 d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed. PMID:27672648

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

PubMed

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.

Surgical treatment of glioblastoma multiforme localized in the motor area of the brain using the technique of cortical electrostimulation.

PubMed

Bogosavljevic, Vojislav; Tasic, Goran; Nestorovic, Branislav; Jovanovic, Vladimir; Rakic, Miodrag; Samardzic, Miroslav

2012-01-01

Glioblastoma multiforme in the motor area is the surgical challenge because of the need for more radical resection in order to extend the life of the patient, and the risk that radicalism could lead to additional neurological deficit. We present series of 26 patients with glioblastoma multiforme localized in and around the motor area, who were hospitalized from October 2004 to February 2009. During all operations, we conducted electrostimulation display area of the brain, to the anatomical location of M1 segment of the motor cortex. Distance of the central sulcus in relation to the coronary suture, measured by magnetic resonance imaging (MRI) was 18.38 mm ± 9.564 mm. The volume of electricity required for a motor response was mean 8.79 ± 1.484 mA, with increasing distance from the coronary suture the amperage required to explicit motor responses decreased. The difference (mm) between the distance from the coronary suture measured using MRI and distances measured electrostimulation smaller and power consumption was less (F = 13.285, p < 0.01). The method of cortical cerebral cortex electrostimulation is simple and safe method and a binding protocol to the patient safe operation glioblastoma multiforme localized in the motor area of the brain.

Accounting for interim safety monitoring of an adverse event upon termination of a clinical trial.

PubMed

Dallas, Michael J

2008-01-01

Upon termination of a clinical trial that uses interim evaluations to determine whether the trial can be stopped, a proper statistical analysis must account for the interim evaluations. For example, in a group-sequential design where the efficacy of a treatment regimen is evaluated at interim stages, and the opportunity to stop the trial based on positive efficacy findings exists, the terminal p-value, point estimate, and confidence limits of the outcome of interest must be adjusted to eliminate bias. While it is standard practice to adjust terminal statistical analyses due to opportunities to stop for "positive" findings, adjusting due to opportunities to stop for "negative" findings is also important. Stopping rules for negative findings are particularly useful when monitoring a specific rare serious adverse event in trials designed to show safety with respect to the event. In these settings, establishing conservative stopping rules are appropriate, and therefore accounting for the interim monitoring can have a substantial effect on the final results. Here I present a method to account for interim safety monitoring and illustrate its usefulness. The method is demonstrated to have advantages over methodology that does not account for interim monitoring.

c-MYC inhibition impairs hypoxia response in glioblastoma multiforme

PubMed Central

Falchetti, Maria Laura; Illi, Barbara; Bozzo, Francesca; Valle, Cristiana; Helmer-Citterich, Manuela; Ferrè, Fabrizio; Nasi, Sergio; Levi, Andrea

2016-01-01

The c-MYC oncoprotein is a DNA binding transcription factor that enhances the expression of many active genes. c-MYC transcriptional signatures vary according to the transcriptional program defined in each cell type during differentiation. Little is known on the involvement of c-MYC in regulation of gene expression programs that are induced by extracellular cues such as a changing microenvironment. Here we demonstrate that inhibition of c-MYC in glioblastoma multiforme cells blunts hypoxia-dependent glycolytic reprogramming and mitochondria fragmentation in hypoxia. This happens because c-MYC inhibition alters the cell transcriptional response to hypoxia and finely tunes the expression of a subset of Hypoxia Inducible Factor 1-regulated genes. We also show that genes whose expression in hypoxia is affected by c-MYC inhibition are able to distinguish the Proneural subtype of glioblastoma multiforme, thus potentially providing a molecular signature for this class of tumors that are the least tractable among glioblastomas. PMID:27119353

Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delattre, J.Y.; Safai, B.; Posner, J.B.

1988-02-01

In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder ismore » probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice.« less

Mycoplasma pneumoniae-Induced Mucocutaneous Rash: A New Syndrome Distinct from Erythema Multiforme? Report of a New Case and Review of the Literature.

PubMed

Martínez-Pérez, M; Imbernón-Moya, A; Lobato-Berezo, A; Churruca-Grijelmo, M

2016-09-01

Respiratory tract infection due to Mycoplasma pneumoniae can provoke cutaneous and mucosal rashes, which have been classified within the spectrum of erythema multiforme or Stevens-Johnson syndrome. This classification is of therapeutic and prognostic importance and has generated intense debate in the literature. A recent systematic review of 202 cases of mucocutaneous rashes associated with M. pneumoniae infection concluded that these rashes might constitute a distinct entity, for which the term Mycoplasma-induced rash and mucositis was proposed. We describe a patient with acute M pneumoniae respiratory tract infection who presented mucosal and cutaneous lesions that were difficult to classify as erythema multiforme or Stevens-Johnson syndrome; the lesions were compatible with the proposed new disease. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

MR-guided laser-induced interstitial thermotherapy of recurrent glioblastoma multiforme: preliminary results in 16 patients.

PubMed

Schwarzmaier, Hans-Joachim; Eickmeyer, Frank; von Tempelhoff, Wernholt; Fiedler, Volkhard Ulrich; Niehoff, Hendrik; Ulrich, Slif Dagobert; Yang, Qin; Ulrich, Frank

2006-08-01

We investigated the survival after laser-induced interstitial thermotherapy in 16 patients suffering from recurrent glioblastoma multiforme. The concept underlying the intervention is the cytoreduction of the tumor tissue by local thermocoagulation. All patients received standard chemotherapy (temozolomide). The median overall survival time after the first relapse was 9.4 months, corresponding to a median overall survival time after laser irradiation of 6.9 months. During the study, however, the median survival after laser coagulation increased to 11.2 months. This survival time is substantially longer than those reported for the natural history (<5 months) or after chemotherapy (temozolomide: 5.4-7.1 months). We conclude that cytoreduction by laser irradiation might be a promising option for patients suffering from recurrent glioblastoma multiforme. In addition, the data indicate the presence of a substantial learning curve. Future work should optimize the therapeutic regimen and evaluate this treatment approach in controlled clinical trials.

Analysis of Transportation Options for Commercial Spent Fuel in the U.S.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalinina, Elena; Busch, Ingrid Karin

The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S.more » Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF)...« less

Soy Metabolites, Isoflavones in Cell Growth and Apoptosis

DTIC Science & Technology

2000-07-01

previously PROTEINS BY APIGENIN IS P21/WAF1 INDEPENDENT. M McVean, W C shown that genistein, at 5MM, can block invasion of glioblastoma multiforme into...may Kansas City, KS be involved in the invasion of glioblastoma multiforme into FBRA. These studies Apigenin , a nonmutagenic flavonoid, has been shown...p21/wafl in modulating cell cycle regulatory lion mechanisms. In C6 rat glioma cells and U87 human glioma cells treated with proteins during apigenin

Survival benefit of surgery in recurrent glioblastoma multiforme.

PubMed

Choudry, Usama Khalid; Khan, Saad Akhtar; Shamim, Muhammad Shahzad

2017-12-01

There is an ongoing debate regarding role of surgery for recurrent glioblastoma multiforme (GBM). Older literature hinted at only modest survival benefits with surgery and a high rate of morbidity. However, more recent literature suggests better survival that may be attributed to better surgical techniques and better options in adjuvant treatment. Herein the authors review recent literature with regards to the possible role of surgery in recurrent GBM and also look into the key factors impacting second surgery. .

Cost Sensitivity Analysis for Consolidated Interim Storage of Spent Fuel: Evaluating the Effect of Economic Environment Parameters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cumberland, Riley M.; Williams, Kent Alan; Jarrell, Joshua J.

This report evaluates how the economic environment (i.e., discount rate, inflation rate, escalation rate) can impact previously estimated differences in lifecycle costs between an integrated waste management system with an interim storage facility (ISF) and a similar system without an ISF.

78 FR 48503 - Proposed Revision to Missiles Generated by Extreme Winds

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

...-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants: LWR..., ``Design-Basis Hurricane and Hurricane Missiles for Nuclear Power Plants,'' and Interim Staff Guidance DC... and Hurricane Missiles for Nuclear Power Plants'' (ADAMS, Accession No. ML110940300), and Interim...

A phase II flexible screening design allowing for interim analysis and comparison with historical control.

PubMed

Wu, Wenting; Bot, Brian; Hu, Yan; Geyer, Susan M; Sargent, Daniel J

2013-07-01

Sargent and Goldberg [1] proposed a randomized phase II flexible screening design (SG design) which took multiple characteristics of candidate regimens into consideration in selecting a regimen for further phase III testing. In this paper, we extend the SG design by including provisions for an interim analysis and/or a comparison to a historical control. By including a comparison with a historical control, a modified SG design not only identifies a more promising treatment but also assures that the regimen has a clinically meaningful level of efficacy as compared to a historical control. By including an interim analysis, a modified SG design could reduce the number of patients exposed to inferior treatment regimens. When compared to the original SG design, the modified designs increase the sample size moderately, but expand the utility of the flexible screening design substantially. Copyright © 2013 Elsevier Inc. All rights reserved.

Re-use of pilot data and interim analysis of pivotal data in MRMC studies: a simulation study

NASA Astrophysics Data System (ADS)

Chen, Weijie; Samuelson, Frank; Sahiner, Berkman; Petrick, Nicholas

2017-03-01

Novel medical imaging devices are often evaluated with multi-reader multi-case (MRMC) studies in which radiologists read images of patient cases for a specified clinical task (e.g., cancer detection). A pilot study is often used to measure the effect size and variance parameters that are necessary for sizing a pivotal study (including sizing readers, non-diseased and diseased cases). Due to the practical difficulty of collecting patient cases or recruiting clinical readers, some investigators attempt to include the pilot data as part of their pivotal study. In other situations, some investigators attempt to perform an interim analysis of their pivotal study data based upon which the sample sizes may be re-estimated. Re-use of the pilot data or interim analyses of the pivotal data may inflate the type I error of the pivotal study. In this work, we use the Roe and Metz model to simulate MRMC data under the null hypothesis (i.e., two devices have equal diagnostic performance) and investigate the type I error rate for several practical designs involving re-use of pilot data or interim analysis of pivotal data. Our preliminary simulation results indicate that, under the simulation conditions we investigated, the inflation of type I error is none or only marginal for some design strategies (e.g., re-use of patient data without re-using readers, and size re-estimation without using the effect-size estimated in the interim analysis). Upon further verifications, these are potentially useful design methods in that they may help make a study less burdensome and have a better chance to succeed without substantial loss of the statistical rigor.

Poison ivy: an underreported cause of erythema multiforme.

PubMed

Werchniak, Andrew E; Schwarzenberger, Kathryn

2004-11-01

The relationship between herpes simplex virus (HSV) and erythema multiforme (EM) has been well described. Many authors contend that EM (excluding Stevens-Johnson syndrome and toxic epidermal necrolysis) occurs almost exclusively as a response to HSV infection. During the past year, however, we have observed several cases of EM complicating severe Rhus allergic contact dermatitis. Although this association has been previously documented, the paucity of cases in the literature, along with our experience, suggests that this is an underreported phenomenon. We describe 4 of our cases.

Conditional power and predictive power based on right censored data with supplementary auxiliary information.

PubMed

Sun, Libo; Wan, Ying

2018-04-22

Conditional power and predictive power provide estimates of the probability of success at the end of the trial based on the information from the interim analysis. The observed value of the time to event endpoint at the interim analysis could be biased for the true treatment effect due to early censoring, leading to a biased estimate of conditional power and predictive power. In such cases, the estimates and inference for this right censored primary endpoint are enhanced by incorporating a fully observed auxiliary variable. We assume a bivariate normal distribution of the transformed primary variable and a correlated auxiliary variable. Simulation studies are conducted that not only shows enhanced conditional power and predictive power but also can provide the framework for a more efficient futility interim analysis in terms of an improved accuracy in estimator, a smaller inflation in type II error and an optimal timing for such analysis. We also illustrated the new approach by a real clinical trial example. Copyright © 2018 John Wiley & Sons, Ltd.

Expression differences of programmed death ligand 1 in de-novo and recurrent glioblastoma multiforme

PubMed Central

Heynckes, Sabrina; Gaebelein, Annette; Haaker, Gerrit; Grauvogel, Jürgen; Franco, Pamela; Mader, Irina; Carro, Maria Stella; Prinz, Marco; Delev, Daniel; Schnell, Oliver; Heiland, Dieter Henrik

2017-01-01

The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits. We show that PD-L1 expression was reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide (TMZ) chemotherapy showed a significantly reduced level of PD-L1 expression in the recurrence stage compared to the corresponding de-novo tumour. Our findings may provide an explanation for potentially lower response to immunotherapy in the recurrent stage due to the reduced expression of the therapeutic target PD-L1. PMID:29088776

Suppression of survivin expression in glioblastoma cells by the Ras inhibitor farnesylthiosalicylic acid promotes caspase-dependent apoptosis.

PubMed

Blum, Roy; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Kloog, Yoel

2006-09-01

The Ras inhibitor farnesylthiosalicylic acid (FTS) has been shown to induce apoptosis in glioblastoma multiforme, but its mechanism of action was unknown. We show that FTS or dominant-negative Ras, by deregulating extracellular signal-regulated kinase and Akt signaling, decreases survivin gene transcripts in U87 glioblastoma multiforme, leading to disappearance of survivin protein and cell death. FTS affected both Ras-controlled regulators of survivin transcription and Ras-regulated survival signals. Thus, Ras inhibition by FTS resulted in release of the survivin "brake" on apoptosis and in activation of the mitochondrial apoptotic pathway: dephosphorylation of Bad, activation of Bax, release of cytochrome c, and caspase activation. FTS-induced apoptosis of U87 cells was strongly attenuated by forced expression of survivin or by caspase inhibitors. These results show that resistance to apoptosis in glioblastoma multiforme can be abolished by a single Ras inhibitor, which targets both survivin, a critical inhibitor of apoptosis, and the intrinsic mitochondrial apoptotic machinery.

Development of a novel mouse glioma model using lentiviral vectors

PubMed Central

Marumoto, Tomotoshi; Tashiro, Ayumu; Friedmann-Morvinski, Dinorah; Scadeng, Miriam; Soda, Yasushi; Gage, Fred H; Verma, Inder M

2009-01-01

We report the development of a new method to induce glioblastoma multiforme in adult immunocompetent mice by injecting Cre-loxP–controlled lentiviral vectors expressing oncogenes. Cell type- or region-specific expression of activated forms of the oncoproteins Harvey-Ras and AKT in fewer than 60 glial fibrillary acidic protein–positive cells in the hippocampus, subventricular zone or cortex of mice heterozygous for the gene encoding the tumor suppressor Tp53 were tested. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. However, tumors were rarely detected when the mice were transduced in the cortex. Transplantation of brain tumor cells into naive recipient mouse brain resulted in the formation of glioblastoma multiforme–like tumors, which contained CD133+ cells, formed tumorspheres and could differentiate into neurons and astrocytes. We suggest that the use of Cre-loxP–controlled lentiviral vectors is a novel way to generate a mouse glioblastoma multiforme model in a region- and cell type-specific manner in adult mice. PMID:19122659

Semiautomated Workflow for Clinically Streamlined Glioma Parametric Response Mapping

PubMed Central

Keith, Lauren; Ross, Brian D.; Galbán, Craig J.; Luker, Gary D.; Galbán, Stefanie; Zhao, Binsheng; Guo, Xiaotao; Chenevert, Thomas L.; Hoff, Benjamin A.

2017-01-01

Management of glioblastoma multiforme remains a challenging problem despite recent advances in targeted therapies. Timely assessment of therapeutic agents is hindered by the lack of standard quantitative imaging protocols for determining targeted response. Clinical response assessment for brain tumors is determined by volumetric changes assessed at 10 weeks post-treatment initiation. Further, current clinical criteria fail to use advanced quantitative imaging approaches, such as diffusion and perfusion magnetic resonance imaging. Development of the parametric response mapping (PRM) applied to diffusion-weighted magnetic resonance imaging has provided a sensitive and early biomarker of successful cytotoxic therapy in brain tumors while maintaining a spatial context within the tumor. Although PRM provides an earlier readout than volumetry and sometimes greater sensitivity compared with traditional whole-tumor diffusion statistics, it is not routinely used for patient management; an automated and standardized software for performing the analysis and for the generation of a clinical report document is required for this. We present a semiautomated and seamless workflow for image coregistration, segmentation, and PRM classification of glioblastoma multiforme diffusion-weighted magnetic resonance imaging scans. The software solution can be integrated using local hardware or performed remotely in the cloud while providing connectivity to existing picture archive and communication systems. This is an important step toward implementing PRM analysis of solid tumors in routine clinical practice. PMID:28286871

Conditional estimation using prior information in 2-stage group sequential designs assuming asymptotic normality when the trial terminated early.

PubMed

Shimura, Masashi; Maruo, Kazushi; Gosho, Masahiko

2018-04-23

Two-stage designs are widely used to determine whether a clinical trial should be terminated early. In such trials, a maximum likelihood estimate is often adopted to describe the difference in efficacy between the experimental and reference treatments; however, this method is known to display conditional bias. To reduce such bias, a conditional mean-adjusted estimator (CMAE) has been proposed, although the remaining bias may be nonnegligible when a trial is stopped for efficacy at the interim analysis. We propose a new estimator for adjusting the conditional bias of the treatment effect by extending the idea of the CMAE. This estimator is calculated by weighting the maximum likelihood estimate obtained at the interim analysis and the effect size prespecified when calculating the sample size. We evaluate the performance of the proposed estimator through analytical and simulation studies in various settings in which a trial is stopped for efficacy or futility at the interim analysis. We find that the conditional bias of the proposed estimator is smaller than that of the CMAE when the information time at the interim analysis is small. In addition, the mean-squared error of the proposed estimator is also smaller than that of the CMAE. In conclusion, we recommend the use of the proposed estimator for trials that are terminated early for efficacy or futility. Copyright © 2018 John Wiley & Sons, Ltd.

Evaluation of ERA-interim and MERRA Cloudiness in the Southern Oceans

NASA Technical Reports Server (NTRS)

Naud, Catherine M.; Booth, James F.; Del Genio, Anthony D.

2014-01-01

The Southern Ocean cloud cover modeled by the Interim ECMWF Re-Analysis (ERA-Interim) and Modern- Era Retrospective Analysis for Research and Applications (MERRA) reanalyses are compared against Moderate Resolution Imaging Spectroradiometer (MODIS) and Multiangle Imaging Spectroradiometer (MISR) observations. ERA-Interim monthly mean cloud amounts match the observations within 5%, while MERRA significantly underestimates the cloud amount. For a compositing analysis of clouds in warm season extratropical cyclones, both reanalyses show a low bias in cloud cover. They display a larger bias to the west of the cyclones in the region of subsidence behind the cold fronts. This low bias is larger for MERRA than for ERA-Interim. Both MODIS and MISR retrievals indicate that the clouds in this sector are at a low altitude, often composed of liquid, and of a broken nature. The combined CloudSat-Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) cloud profiles confirm these passive observations, but they also reveal that low-level clouds in other parts of the cyclones are also not properly represented in the reanalyses. The two reanalyses are in fairly good agreement for the dynamic and thermodynamic characteristics of the cyclones, suggesting that the cloud, convection, or boundary layer schemes are the problem instead. An examination of the lower-tropospheric stability distribution in the cyclones from both reanalyses suggests that the parameterization of shallow cumulus clouds may contribute in a large part to the problem. However, the differences in the cloud schemes and in particular in the precipitation processes, which may also contribute, cannot be excluded.

GlioLab-a space system for Glioblastoma multiforme cells on orbit behavior study

NASA Astrophysics Data System (ADS)

Cappelletti, Chantal; Twiggs, Robert J.

Microgravity conditions and ionizing radiation pose significant health risks for human life in space. This is a concern for future missions and also for future space tourism flights. Nev-ertheless, at the same time it is very interesting to study the effects of these conditions in unhealthy organism like biological samples affected by cancer. It is possible that space envi-ronment increases, decreases or doesn't have any effect on cancer cells. In any case the test results give important informations about cancer treatment or space tourism flight for people affected by cancer. GlioLab is a joint project between GAUSS-Group of Astrodynamics at the "Sapienza" University of Roma and the Morehead State University (MSU) Space Science Center in Kentucky. The main goal of this project is the design and manufacturing of an autonomous space system to investigate potential effects of the space environment exposure on a human glioblastoma multiforme cell line derived from a 65-year-old male and on Normal Human Astrocytes (NHA). In particular the samples are Glioblastoma multiforme cancer cells because the radiotherapy using ionizing radiation is the only treatment after surgery that can give on ground an improvement on the survival rate for this very malignant cancer. During a mission on the ISS, GlioLab mission has to test the in orbit behavior of glioblastoma cancer cells and healthy neuronal cells, which are extremely fragile and require complex experimentation and testing. In this paper engineering solutions to design and manufacturing of an autonomous space system that can allow to keep alive these kind of cells are described. This autonomous system is characterized also by an optical device dedicated to cells behavior analysis and by microdosimeters for monitoring space radiation environment.

Quantitative proteomic analysis reveals effects of epidermal growth factor receptor (EGFR) on invasion-promoting proteins secreted by glioblastoma cells.

PubMed

Sangar, Vineet; Funk, Cory C; Kusebauch, Ulrike; Campbell, David S; Moritz, Robert L; Price, Nathan D

2014-10-01

Glioblastoma multiforme is a highly invasive and aggressive brain tumor with an invariably poor prognosis. The overexpression of epidermal growth factor receptor (EGFR) is a primary influencer of invasion and proliferation in tumor cells and the constitutively active EGFRvIII mutant, found in 30-65% of Glioblastoma multiforme, confers more aggressive invasion. To better understand how EGFR contributes to tumor aggressiveness, we investigated the effect of EGFR on the secreted levels of 65 rationally selected proteins involved in invasion. We employed selected reaction monitoring targeted mass spectrometry using stable isotope labeled internal peptide standards to quantity proteins in the secretome from five GBM (U87) isogenic cell lines in which EGFR, EGFRvIII, and/or PTEN were expressed. Our results show that cell lines with EGFR overexpression and constitutive EGFRvIII expression differ remarkably in the expression profiles for both secreted and intracellular signaling proteins, and alterations in EGFR signaling result in reproducible changes in concentrations of secreted proteins. Furthermore, the EGFRvIII-expressing mutant cell line secretes the majority of the selected invasion-promoting proteins at higher levels than other cell lines tested. Additionally, the intracellular and extracellular protein measurements indicate elevated oxidative stress in the EGFRvIII-expressing cell line. In conclusion, the results of our study demonstrate that EGFR signaling has a significant effect on the levels of secreted invasion-promoting proteins, likely contributing to the aggressiveness of Glioblastoma multiforme. Further characterization of these proteins may provide candidates for new therapeutic strategies and targets as well as biomarkers for this aggressive disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Different predictive values of interim 18F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma.

PubMed

Kim, Jihyun; Lee, Jeong-Ok; Paik, Jin Ho; Lee, Won Woo; Kim, Sang Eun; Song, Yoo Sung

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of 18 F-fluoro-2-dexoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim 18 F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim 18 F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling. We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim 18 F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans' algorithm. In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim 18 F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim 18 F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in non-GCB subtype of DLBCL. Interim 18 F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for interim 18 F-FDG PET/CT practice.

A Process Evaluation of Project Developmental Continuity. Interim Report VI: Executive Summary. Recommendations for Continuing the Impact Study.

ERIC Educational Resources Information Center

Granville, Arthur C.; Love, John M.

This brief report summarizes the analysis and conclusions presented in detail in Interim Report VI regarding the feasibility of conducting a longitudinal study of Project Developmental Continuity (PDC). This project is a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and…

Interim Assessment Data: A Case Study on Modifying Instruction Based on Benchmark Feedback

ERIC Educational Resources Information Center

Lange, Tracey M.

2014-01-01

The role of data analysis in the jobs of instructional leaders has become as commonplace as teachers creating lesson plans and taking roll in the classroom. Teachers and building leaders routinely use interim assessment data to develop thoughtful and robust instructional plans that address identified areas of student need. The link between the…

A global validation of ERA-Interim integrated water vapor estimates using ground-based GNSS observations

NASA Astrophysics Data System (ADS)

Ahmed, F.; Dousa, J.; Hunegnaw, A.; Teferle, F. N.; Bingley, R.

2017-12-01

Integrated water vapor (IWV) derived from climate reanalysis models, such as the European Centre for Medium-range Weather Forecasts (ECMWF) ReAnalysis-Interim (ERA-Interim), is widely used in many atmospheric applications. Therefore, it is of interest to assess the quality of this reanalysis product using available observations. Observations from Global Navigation Satellite Systems (GNSS) are, as of now, available for a period of over 2 decades and their global availability makes it possible to validate the IWV obtained from climate reanalysis models in different geographical and climatic regions. In this study, primarily, three 5-year long homogeneously reprocessed GNSS-derived IWV datasets containing over 400 globally distributed ground-based GNSS stations have been used to validate the IWV estimates obtained from the ERA-Interim climate reanalysis model in 25 different climate zones. The IWV from ERA-Interim has been obtained by vertically integrating the specific humidity at all model levels above the locations of GNSS stations. It has been studied how the difference between the ERA-Interim IWV and the GNSS-derived IWV varies with respect to the different climate zones as well as with respect to the difference in the model orography and latitude. The results show a dependence of the ability of ERA-Interim to model the IWV on difference in climate types and latitude. This dependence, however, is dictated by the concentration of water vapor in different climate zones and at different latitudes. Furthermore, as a secondary focus of this study, the weighted mean atmospheric temperature (Tm) obtained from ERA-Interim has been compared to its equivalent obtained using two widely used approximations globally.

Interim reliability-evaluation program: analysis of the Browns Ferry, Unit 1, nuclear plant. Appendix C - sequence quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

1982-07-01

This report describes a risk study of the Browns Ferry, Unit 1, nuclear plant. The study is one of four such studies sponsored by the NRC Office of Research, Division of Risk Assessment, as part of its Interim Reliability Evaluation Program (IREP), Phase II. This report is contained in four volumes: a main report and three appendixes. Appendix C generally describes the methods used to estimate accident sequence frequency values. Information is presented concerning the approach, example collection, failure data, candidate dominant sequences, uncertainty analysis, and sensitivity analysis.

Have first-time medical school deans been serving longer than we thought? A 50-year analysis.

PubMed

Keyes, Joseph A; Alexander, Hershel; Jarawan, Hani; Mallon, William T; Kirch, Darrell G

2010-12-01

To describe the lengths of service of deans at accredited U.S. MD-granting medical schools from academic years 1959 to 2008 and to determine whether the median length of service of deans changed over time. The authors used the database of the Council of Deans of the Association of American Medical Colleges to seek data, from July 1, 1959 to June 30, 2009, on lengths of service of 842 deans and interim deans at all 125 accredited U.S. MD-granting medical schools existing in 2007. All but 8 schools verified their data, which included the date of the beginning of service, the date of the end of service, and whether the individual served in a permanent or interim capacity. Across five-year cohorts of the first-time deans and interim deans studied, the median length of service was 4.4 years. When the authors excluded individuals who were interim deans exclusively and focused the analysis on the 639 persons who were "permanent" deans, the median length of service was 6.0 years across five-year cohorts. Analysis of one-year cohorts of deans showed similar results (median = 6.1 years), although the medians for six of the seven most recent one-year cohorts ranged from 5.0 to 5.7 years. Through cohort analysis, the median length of service of permanent medical school deans was longer than that found in previous studies, and it has remained relatively stable.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 1: Findings from the PDC Implementation Study.

ERIC Educational Resources Information Center

Smith, Allen G.; And Others

This third year interim report, one of a series of documents on the evaluation of Project Developmental Continuity (PDC), presents findings from three major analyses of program implementation; measurement of the extent each program has implemented the basic PDC Guidelines; a description of patterns of that implementation; and analysis of some…

Comparisons of Cooperative and Non-Cooperative Students: An Analysis of Student Accounting System Data. Interim Report, June, 1981.

ERIC Educational Resources Information Center

Frazier, Don

The major purpose of this study was to identify unique effects of cooperative vocational education. This interim report is of results of the analyses of existing data bases. Comparisons of cooperative and non-cooperative vocational programs are made on the following variables: enrollments by age, sex and race, school status, work status,…

National Home Start Evaluation Interim Report VII. Twenty-Month Program Analysis and Findings.

ERIC Educational Resources Information Center

Love, John M.; And Others

This interim evaluation report focuses on process (formative) and outcome (summative) data collected in spring 1975 on the National Home Start Program. Home Start, a federally-funded 3-year (1972-1975) home-based demonstration program for low-income families with 3- to 5-year-old children was designed to enhance a mother's skills in dealing with…

Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme.

PubMed

Liu, Yongji; Shi, Ling; Liu, Yuan; Li, Peng; Jiang, Guoping; Gao, Xiaoning; Zhang, Yongbin; Jiang, Chuanwu; Zhu, Weiping; Han, Hongxing; Ju, Fang

2018-04-01

Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays. Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ. Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint.

PubMed

Tang, Zhongwen

2015-01-01

An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis.

PubMed

Li, Qi; Jia, Hongmei; Li, Haowen; Dong, Chengya; Wang, Yajie; Zou, Zhongmei

2016-11-01

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are involved in their cell proliferation, apoptosis, angiogenesis, and invasion. The functional roles of lncRNAs in GBM are less known. We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas. The differently expressed lncRNAs and mRNA were subjected to construct lncRNA-mRNA co-expression network. Probable functions for lncRNAs were predicted according to lncRNA-mRNA network and genomic adjacency by GO and pathway analysis. The expression of lncRNAs and mRNAs in GBM tissues versus normal brain tissues was examined by quantitative reverse transcription polymerase chain reaction. The 398 lncRNAs and 1995 mRNAs were identified as distinctively expressed in GBM. Probable functional roles for 98 lncRNAs were involved in 30 pathways and 32 gene functions related to tumorigenesis, development, and metastasis. The identified sets of key lncRNAs specific to GBM were subsequently verified by experiment in GBM tissues. Our reports predict the biological functions of a multitude of lncRNAs in GBM that could be potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, our research provides a road map for the identification and analysis of lncRNAs in tumors.

Cryo-image Analysis of Tumor Cell Migration, Invasion, and Dispersal in a Mouse Xenograft Model of Human Glioblastoma Multiforme

PubMed Central

Qutaish, Mohammed Q.; Sullivant, Kristin E.; Burden-Gulley, Susan M.; Lu, Hong; Roy, Debashish; Wang, Jing; Basilion, James P.; Brady-Kalnay, Susann M.; Wilson, David L.

2012-01-01

Purpose The goals of this study were to create cryo-imaging methods to quantify characteristics (size, dispersal, and blood vessel density) of mouse orthotopic models of glioblastoma multiforme (GBM) and to enable studies of tumor biology, targeted imaging agents, and theranostic nanoparticles. Procedures Green fluorescent protein-labeled, human glioma LN-229 cells were implanted into mouse brain. At 20–38 days, cryo-imaging gave whole brain, 4-GB, 3D microscopic images of bright field anatomy, including vasculature, and fluorescent tumor. Image analysis/visualization methods were developed. Results Vessel visualization and segmentation methods successfully enabled analyses. The main tumor mass volume, the number of dispersed clusters, the number of cells/cluster, and the percent dispersed volume all increase with age of the tumor. Histograms of dispersal distance give a mean and median of 63 and 56 μm, respectively, averaged over all brains. Dispersal distance tends to increase with age of the tumors. Dispersal tends to occur along blood vessels. Blood vessel density did not appear to increase in and around the tumor with this cell line. Conclusion Cryo-imaging and software allow, for the first time, 3D, whole brain, microscopic characterization of a tumor from a particular cell line. LN-229 exhibits considerable dispersal along blood vessels, a characteristic of human tumors that limits treatment success. PMID:22125093

Targeting EGFRvIII for glioblastoma multiforme.

PubMed

Yang, Ju; Yan, Jing; Liu, Baorui

2017-09-10

Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive probability methods for interim monitoring in clinical trials with longitudinal outcomes.

PubMed

Zhou, Ming; Tang, Qi; Lang, Lixin; Xing, Jun; Tatsuoka, Kay

2018-04-17

In clinical research and development, interim monitoring is critical for better decision-making and minimizing the risk of exposing patients to possible ineffective therapies. For interim futility or efficacy monitoring, predictive probability methods are widely adopted in practice. Those methods have been well studied for univariate variables. However, for longitudinal studies, predictive probability methods using univariate information from only completers may not be most efficient, and data from on-going subjects can be utilized to improve efficiency. On the other hand, leveraging information from on-going subjects could allow an interim analysis to be potentially conducted once a sufficient number of subjects reach an earlier time point. For longitudinal outcomes, we derive closed-form formulas for predictive probabilities, including Bayesian predictive probability, predictive power, and conditional power and also give closed-form solutions for predictive probability of success in a future trial and the predictive probability of success of the best dose. When predictive probabilities are used for interim monitoring, we study their distributions and discuss their analytical cutoff values or stopping boundaries that have desired operating characteristics. We show that predictive probabilities utilizing all longitudinal information are more efficient for interim monitoring than that using information from completers only. To illustrate their practical application for longitudinal data, we analyze 2 real data examples from clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 3: Assessment of Program Impact Through the Head Start Year.

ERIC Educational Resources Information Center

Granville, Arthur C.; And Others

This interim report, part of a series of documents examining the feasibility of the longitudinal evaluation of Project Developmental Continuity (PDC), presents the results of an analysis of PDC impact at the Head Start level, using Spring 1977 data. PDC is a Head Start Demonstration Program aimed at providing educational and developmental…

Effectiveness Monitoring Report, MWMF Tritium Phytoremediation Interim Measures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hitchcock, Dan; Blake, John, I.

2003-02-10

This report describes and presents the results of monitoring activities during irrigation operations for the calendar year 2001 of the MWMF Interim Measures Tritium Phytoremediation Project. The purpose of this effectiveness monitoring report is to provide the information on instrument performance, analysis of CY2001 measurements, and critical relationships needed to manage irrigation operations, estimate efficiency and validate the water and tritium balance model.

Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism.

PubMed

Didenko, Vladimir V; Ngo, Hop N; Minchew, Candace; Baskin, David S

2002-03-01

The goal of this study was to investigate whether apoptosis occurs in T lymphocytes that invade Fas ligand (FasL)-expressing glioblastomas multiforme (GBMs) and if its induction could be mediated by Fas. Apoptotic T lymphocytes were detected in GBMs by using detection of cell-type markers combined with active caspase-3 immunohistochemical analysis, a recently introduced apoptosis-specific in situ ligation assay, as well as by examining morphological criteria. Apoptotic T cells expressed Fas and were localized in the vicinity or in direct contact with FasL-expressing tumor cells. The T lymphocytes were undergoing apoptosis in spite of Bcl-2 expression. Expression of Bax was also detected in dying T cells, which can explain the absence of the protective effect of Bcl-2. because Bax inhibits Bcl-2 death-repressor activity. On the basis of the data presented in this paper, the authors suggest that GBM cells that express FasL can induce apoptosis in invading immune cells. This phenomenon may play an important role in these tumors' maintenance of immune privilege and evasion of immune attacks. Awareness of this phenomenon should be helpful for the development of novel strategies for treatment of malignant gliomas.

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

PubMed

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 < 0.05). Across different 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.

Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme1

PubMed Central

Badruddoja, Michael A.; Penne, Kara; Desjardins, Annick; Reardon, David A.; Rich, Jeremy N.; Quinn, Jennifer A.; Sathornsumetee, Sith; Friedman, Allan H.; Bigner, Darell D.; Herndon, James E.; Cahill, Ann; Friedman, Henry S.; Vredenburgh, James J.

2007-01-01

Cloretazine (VNP40101M) is a newly synthesized alkylating agent belonging to a novel class of alkylating agents called 1,2-bis(sulfonyl)hydrazines. Agents that belong to this class do not produce vinylating and chloroethylating species, and hence this class of alkylating agents is thought to have minimal systemic toxicity. Cloretazine produces two short-lived active species: 1,2-bis(methylsulfonyl)-1-(2-chloroethyl) hydrazine (a chloroethylating species) and a thiophilic carbamoylating methylisocyanate species. The chloroethylating species preferentially produces lesions at the O6 position of guanine. The methylisocyanate species may inhibit O6-alkylguanine-DNA alkyltransferase, an important mechanism of resistance against alkylating agents. The purpose of this study was to determine the efficacy and tolerability of Cloretazine in patients with recurrent glioblastoma multiforme. The basis for the determination of efficacy was the proportion of patients alive without evidence of disease progression six months after initiation of treatment. Patients with recurrent glioblastoma multiforme received Cloretazine (300 mg/m2) intravenously every six weeks. Radiographic response, survival data, and toxicity were assessed. Thirty-two patients were enrolled. Median age was 56 years; 24 patients (75%) were men. At six months, two patients were alive and progression free, so the six-month progression-free survival (PFS) was 6%. The median PFS was 6.3 weeks. There were no objective radiographic responses. Twelve patients had stable disease for at least one cycle, but only two patients received more than three cycles. Nine patients experienced grade 4 thrombocytopenia and three patients experienced grade 4 neutropenia. Cloretazine administered every six weeks was relatively well tolerated, although this schedule has insignificant activity for patients with recurrent glioblastoma multiforme PMID:17108065

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

PubMed

Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

2017-11-01

To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

Capitation funding of primary health organisations in New Zealand: are enrolled populations being funded according to need?

PubMed

Langton, Jennifer; Crampton, Peter

2008-04-18

To determine whether the three main funding formulas for Primary Health Organisations achieved a stated aim of the Primary Health Care Strategy to fund enrolled populations according to need. National data were obtained from the Ministry of Health for a 12-month period beginning in April 2004: these included demographic characteristics of the enrolled Primary Health Organisation population, plus rates tables for: First-Contact Services, Services to Improve Access, and Health Promotion. Funding for Access and Interim practices for four-quarters was calculated for each of these three funding streams. Analysis of the demographic characteristics of Access and Interim practices was undertaken. Maori and Pacific peoples made up a greater proportion of the Access population than the Interim, had higher rates of deprivation than the non-Maori/non-Pacific population, and demonstrated a younger age distribution. The first quarter (April 2004-June 2004) showed there was preferential funding for Access PHOs and in particular high-needs groups. In quarter two, this level of preferential funding had diminished, coinciding with the introduction of increased government funding for all Interim enrolees aged 65 and over. The greater funding for Access enrolees was notably eroded with the introduction of Access-level funding for those aged 65+ in Interim PHOs. Since these data were analysed all remaining Interim age groups have shifted to Access-level funding, benefiting non-Maori /non-Pacific in Interim PHOs. The rapid shift to Access-level funding for First Contact Services has seen a continued erosion of the redistributive effect of the original needs-based formulas. A system cannot be considered equitable if some members of society are not realising their health potential, and financing of primary care should remain redistributive until such a time as this objective is attained.

Constitutional mismatch repair deficiency presenting in childhood as three simultaneous malignancies.

PubMed

Walter, Andrew W; Ennis, Sara; Best, Hunter; Vaughn, Cecily P; Swensen, Jeffrey J; Openshaw, Amanda; Gripp, Karen W

2013-11-01

A 13-year-old child presented with three simultaneous malignancies: glioblastoma multiforme, Burkitt lymphoma, and colonic adenocarcinoma. She was treated for her diseases without success and died 8 months after presentation. Genetic analysis revealed a homozygous mutation in the PMS2 gene, consistent with constitutional mismatch repair deficiency. Her siblings and parents were screened: three of four siblings and both parents were heterozygous for this mutation; the fourth sibling did not have the mutation. Copyright © 2013 Wiley Periodicals, Inc.

Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

PubMed

Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

2012-08-01

Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

[The Relevance of MicroRNAs in Glioblastoma Stem Cells].

PubMed

Kleinová, R; Slabý, O; Šána, J

2015-01-01

Glioblastoma multiforme is the most common intracranial malignity of astrocyte origin in adults. Despite complex therapy consisting of maximal surgical resection, adjuvant concomitant chemoradiotherapy with temozolomide followed by temozolomide in monotherapy, the median of survival ranges between 12 and 15 months from dia-gnosis. This infaust prognosis is very often caused by both impossibility of achieving of sufficient radical surgical resection and tumor resistance to adjuvant therapy, which relates to the presence of glioblastoma stem cells. Similarly to normal stem cells, glioblastoma stem cells are capable of self -renewal, differentiation, and unlimited slow proliferation. Their resistance to conventional therapy is also due to higher expressions of DNA repair enzymes, antiapoptotic factors and multidrug transporters. Therefore, targeting these unique properties could be a novel promising therapeutic approach leading to more effective therapy and better prognosis of glioblastoma multiforme patients. One of the approaches how to successfully regulate above -mentioned properties is targeted regulation of microRNAs (miRNAs). These small noncoding RNA molecules posttranscriptionally regulate expression of more than 2/ 3 of all human genes that are also involved in stem cell associated signaling pathways. Moreover, deregulated expression of some miRNAs has been observed in many cancers, including glioblastoma multiforme.

Management of elderly patients with glioblastoma-multiforme-a systematic review.

PubMed

Almadani, Asmaa; Sanjay, Dixit; Chris, Rowland-Hill; Shailendra, Achawal; Chitoor, Rajaraman; Gerry, O'Reilly; Robin, Highley; Masood, Hussain; Louise, Baker; Lynne, Gill; Holly, Morris; Mohan, Hingorani

2018-03-09

The management of elderly patients with glioblastoma-multiforme (GBM) remains poorly defined with many experts in the past advocating best supportive care, in view of limited evidence on efficacy of more aggressive treatment protocols. There is randomised evidence (NORDIC and NA-O8 studies) to support the use of surgery followed by adjuvant monotherapy with either radiotherapy (RT) using hypofractionated regimes (e.g. 36 Gy in 6 fractions OR 40 Gy in 15 fractions) or chemotherapy with temozolomide (TMZ) in patients expressing methylation of promoter for O 6 -methylguanine-DNA methyltransferase enzyme. However, the role of combined-modality therapy involving the use of combined RT and TMZ protocols has remained controversial with data from the EORTC (European Organisation for Research and Treatment of Cancer)-NCIC (National Cancer Institute of Canada) studies indicating that patients more than 65 years of age may not benefit significantly from combining standard RT fractionation using 60 Gy in 30 fractions with concurrent and adjuvant TMZ. More recently, randomised data has emerged on combining hypofractionated RT with concurrent and adjuvant TMZ. We provide a comprehensive review of literature with the aim of defining an evidence-based algorithm for management of elderly glioblastoma-multiforme population.

Functions and requirements document for interim store solidified high-level and transuranic waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith-Fewell, M.A., Westinghouse Hanford

1996-05-17

The functions, requirements, interfaces, and architectures contained within the Functions and Requirements (F{ampersand}R) Document are based on the information currently contained within the TWRS Functions and Requirements database. The database also documents the set of technically defensible functions and requirements associated with the solidified waste interim storage mission.The F{ampersand}R Document provides a snapshot in time of the technical baseline for the project. The F{ampersand}R document is the product of functional analysis, requirements allocation and architectural structure definition. The technical baseline described in this document is traceable to the TWRS function 4.2.4.1, Interim Store Solidified Waste, and its related requirements, architecture,more » and interfaces.« less

A Procedure for Structural Weight Estimation of Single Stage to Orbit Launch Vehicles (Interim User's Manual)

NASA Technical Reports Server (NTRS)

Martinovic, Zoran N.; Cerro, Jeffrey A.

2002-01-01

This is an interim user's manual for current procedures used in the Vehicle Analysis Branch at NASA Langley Research Center, Hampton, Virginia, for launch vehicle structural subsystem weight estimation based on finite element modeling and structural analysis. The process is intended to complement traditional methods of conceptual and early preliminary structural design such as the application of empirical weight estimation or application of classical engineering design equations and criteria on one dimensional "line" models. Functions of two commercially available software codes are coupled together. Vehicle modeling and analysis are done using SDRC/I-DEAS, and structural sizing is performed with the Collier Research Corp. HyperSizer program.

On the comparisons of tropical relative humidity in the lower and middle troposphere among COSMIC radio occultations, MERRA and ECMWF data sets

NASA Astrophysics Data System (ADS)

Vergados, P.; Mannucci, A. J.; Ao, C. O.; Jiang, J. H.; Su, H.

2015-01-01

The spatial variability of the tropical tropospheric relative humidity (RH) throughout the vertical extent of the troposphere is examined using Global Positioning System Radio Occultation (GPSRO) observations from the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) mission. These high vertical resolution observations capture the detailed structure and moisture budget of the Hadley Cell circulation. We compare the COSMIC observations with the European Center for Medium-range Weather Forecast (ECMWF) Re-Analysis Interim (ERA-Interim) and the Modern-Era Retrospective analysis for Research and Applications (MERRA) climatologies. Qualitatively, the spatial pattern of RH in all data sets matches up remarkably well, capturing distinct features of the general circulation. However, RH discrepancies exist between ERA-Interim and COSMIC data sets, which are noticeable across the tropical boundary layer. Specifically, ERA-Interim shows a drier Inter Tropical Convergence Zone (ITCZ) by 15-20% compared both to COSMIC and MERRA data sets, but this difference decreases with altitude. Unlike ECMWF, MERRA shows an excellent agreement with the COSMIC observations except above 400 hPa, where GPSRO observations capture drier air by 5-10%. RH climatologies were also used to evaluate intraseasonal variability. The results indicate that the tropical middle troposphere at ±5-25° is most sensitive to seasonal variations. COSMIC and MERRA data sets capture the same magnitude of the seasonal variability, but ERA-Interim shows a weaker seasonal fluctuation up to 10% in the middle troposphere inside the dry air subsidence regions of the Hadley Cell. Over the ITCZ, RH varies by maximum 9% between winter and summer.

Retrospective analysis of bevacizumab in combination with fotemustine in chinese patients with recurrent glioblastoma multiforme.

PubMed

Liu, Zhiguang; Zhang, Guanqun; Zhu, Liang; Wang, Jiangbo; Liu, Dongbo; Lian, Lifei; Liu, Jianlin; Lai, Tianbao; Zhuang, Xiaorong

2015-01-01

The aim of this study was to assess the activity and safety of bevacizumab (BEV) and fotemustine (FTM) for the treatment of recurrent glioblastoma multiforme (GBM) patients and explore the potential prognostic parameters on survival. This study retrospectively analyzed all patients with GBM who were treated with at least one cycle of BEV and FTM from July 2010 to October 2012. A total of 176 patients with recurrent GBM were enrolled. The response rate and disease control rate were 46.6% and 90.9%, respectively. A 6-month PFS rate of 33.3% (95% CI: 26.5%-40.3%) and a median PFS of 5.0 (95% CI: 2.4-7.5) months were observed. The median OS was 8.0 (95% CI: 6.7-9.2) months. Multivariate analysis showed that risk factors with a significant influence on the PFS of all patients were Karnofsky Performance Status (KPS) (≥70 versus <70, HR = 0.53, 95% CI: 0.39-0.73, and P = 0.01) and MGMT status (methylated versus unmethylated, HR = 0.69, 95% CI: 0.52-0.97, and P = 0.04). The most common treatment-related adverse events were fatigue, proteinuria, hypophonia, hypertension, thrombocytopenia, anemia, and neutropenia. In conclusion, combination of BEV with FTM is well tolerated and may derive some clinical benefits in recurrent GBM patients. Higher KPS and MGMT promoter hypermethylation were suggested to be associated with prolonged survival.

Alternative Polyadenylation in Glioblastoma Multiforme and Changes in Predicted RNA Binding Protein Profiles

PubMed Central

Shao, Jiaofang; Zhang, Jing; Zhang, Zengming; Jiang, Huawei; Lou, Xiaoyan; Foltz, Gregory; Lan, Qing; Huang, Qiang

2013-01-01

Abstract Alternative polyadenylation (APA) is widely present in the human genome and plays a key role in carcinogenesis. We conducted a comprehensive analysis of the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline, RNAelements (http://sysbio.zju.edu.cn/RNAelements/), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation (RIP) analysis. We identified 4530 APA isoforms for 2733 genes in GBM, and found that 182 APA isoforms from 148 genes showed significant differential expression between normal and GBM brain tissues. We then focused on three genes with long and short APA isoforms that show inconsistent expression changes between normal and GBM brain tissues. These were myocyte enhancer factor 2D, heat shock factor binding protein 1, and polyhomeotic homolog 1 (Drosophila). Using the RNAelements program, we found that RBP binding sites were enriched in the alternative regions between the first and the last polyadenylation sites, which would result in the short APA forms escaping regulation from those RNA binding proteins. To the best of our knowledge, this report is the first comprehensive APA isoform dataset for GBM and normal brain tissues. Additionally, we demonstrated a putative novel APA-mediated mechanism for controlling RNA stability and translation for APA isoforms. These observations collectively lay a foundation for novel diagnostics and molecular mechanisms that can inform future therapeutic interventions for GBM. PMID:23421905

Core Canonical Pathways Involved in Developing Human Glioblastoma Multiforme (GBM).

PubMed

Ghosh, Somiranjan; Dutta, Sisir; Thorne, Gabriel; Boston, Ava; Barfield, Alexis; Banerjee, Narendra; Walker, Rayshawn; Banerjee, Hirendra Nath

2017-02-01

Glioblastoma multiforme (GBM) is the most common and aggressive type of the primary brain tumors with pathologic hallmarks of necrosis and vascular proliferation. The diagnosis of GBM is currently mostly based on histological examination of brain tumor tissues, after radiological characterization and surgical biopsy. The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis can be made based on molecular profiling with or without histological examination, rather than solely on histological phenotype. The development of novel genomic and proteomic techniques will foster in the identification of such diagnostic and prognostic molecular markers. We analyzed the global differential gene expression of a GBM cell line HTB15 in comparison to normal human Astrocytes, and established a few canonical pathways that are important in determining the molecular mechanisms of cancer using global gene expression microarray, coupled with the Ingenuity Pathway Analysis ( IPA ®). Overall, we revealed a discrete gene expression profile in the experimental model that resembled progression of GBM cancer. The canonical pathway analysis showed the involvement of genes that differentially expressed in such a disease condition that included Inositol pathway, Polo like kinases, nNOS signaling , and Tetrapyrrole biosynthesis . Our findings established that the gene expression pattern of this dreaded brain cancer will probably help the cancer research community by finding out newer therapeutic strategies to combat this dreaded cancer type that leads to the identification of high-risk population in this category, with almost hundred percent mortality rate.

Interim Air Purity Guidelines for Dry Deck Shelter (DDS) Operations

DTIC Science & Technology

1990-10-01

The acceptable limits for gaseous contaminants in submarine compressed air for use as diver’s breathing air are derived from the 8-hour Time Weighted...accompanying documentation. Cylinders must be declared as hazardous cargo (" Air , Compressed Non-Flammable Gas") prior to air transport. Analysis of cylinder...capi NAVAL MEDICAL RESEARCH INSTITUTE Bethesda, MD 20889-5055 NMRI 90-109 October 1990 AD-A231 432 INTERIM AIR PURITY GUIDELINES FOR DRY DECK

Terrestrial gravity data analysis for interim gravity model improvement

NASA Technical Reports Server (NTRS)

1987-01-01

This is the first status report for the Interim Gravity Model research effort that was started on June 30, 1986. The basic theme of this study is to develop appropriate models and adjustment procedures for estimating potential coefficients from terrestrial gravity data. The plan is to use the latest gravity data sets to produce coefficient estimates as well as to provide normal equations to NASA for use in the TOPEX/POSEIDON gravity field modeling program.

Maximum inflation of the type 1 error rate when sample size and allocation rate are adapted in a pre-planned interim look.

PubMed

Graf, Alexandra C; Bauer, Peter

2011-06-30

We calculate the maximum type 1 error rate of the pre-planned conventional fixed sample size test for comparing the means of independent normal distributions (with common known variance) which can be yielded when sample size and allocation rate to the treatment arms can be modified in an interim analysis. Thereby it is assumed that the experimenter fully exploits knowledge of the unblinded interim estimates of the treatment effects in order to maximize the conditional type 1 error rate. The 'worst-case' strategies require knowledge of the unknown common treatment effect under the null hypothesis. Although this is a rather hypothetical scenario it may be approached in practice when using a standard control treatment for which precise estimates are available from historical data. The maximum inflation of the type 1 error rate is substantially larger than derived by Proschan and Hunsberger (Biometrics 1995; 51:1315-1324) for design modifications applying balanced samples before and after the interim analysis. Corresponding upper limits for the maximum type 1 error rate are calculated for a number of situations arising from practical considerations (e.g. restricting the maximum sample size, not allowing sample size to decrease, allowing only increase in the sample size in the experimental treatment). The application is discussed for a motivating example. Copyright © 2011 John Wiley & Sons, Ltd.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

PubMed

Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

2016-05-03

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Survival of patients with glioblastoma multiforme treated by intraoperative high-activity cobalt 60 endocurietherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, P.P.; Good, R.R.; Jones, E.O.

The authors report their initial treatment results in 49 patients with glioblastoma multiforme (GM) who received intraoperative endocurietherapy (ECT) with high-activity cobalt 60 ({sup 60}Co) probe. Thirty poor prognosis (unresectable tumor) patients (Group I) with newly diagnosed GM were treated by either biopsy or subtotal excision, followed by 20.00-Gy single-fraction {sup 60}Co probe ECT, and 60.00-Gy external-beam radiation therapy (EXRT) (80.00 Gy total tumor dose). Nineteen patients (Group II) with recurrent, previously resected and externally irradiated GM were retreated with 20.00-Gy single-fraction {sup 60}Co probe ECT alone. The authors' initial experience with intraoperative ECT of GM is discussed.

Comparative risk assessments for the production and interim storage of glass and ceramic waste forms: Defense waste processing facility

NASA Astrophysics Data System (ADS)

Huang, J. C.; Wright, W. V.

1982-04-01

The Defense Waste Processing Facility (DWPF) for immobilizing nuclear high level waste (HLW) is scheduled to be built. High level waste is produced when reactor components are subjected to chemical separation operations. Two candidates for immobilizing this HLW are borosilicate glass and crystalline ceramic, either being contained in weld sealed stainless steel canisters. A number of technical analyses are being conducted to support a selection between these two waste forms. The risks associated with the manufacture and interim storage of these two forms in the DWPF are compared. Process information used in the risk analysis was taken primarily from a DWPF processibility analysis. The DWPF environmental analysis provided much of the necessary environmental information.

Interim reliability-evaluation program: analysis of the Browns Ferry, Unit 1, nuclear plant. Appendix B - system descriptions and fault trees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

1982-07-01

This report describes a risk study of the Browns Ferry, Unit 1, nuclear plant. The study is one of four such studies sponsored by the NRC Office of Research, Division of Risk Assessment, as part of its Interim Reliability Evaluation Program (IREP), Phase II. This report is contained in four volumes: a main report and three appendixes. Appendix B provides a description of Browns Ferry, Unit 1, plant systems and the failure evaluation of those systems as they apply to accidents at Browns Ferry. Information is presented concerning front-line system fault analysis; support system fault analysis; human error models andmore » probabilities; and generic control circuit analyses.« less

How well do Reanalysis represent polar lows?

NASA Astrophysics Data System (ADS)

Zappa, G.; Shaffrey, L.; Hodges, K.

2013-12-01

Polar lows are intense maritime mesocyclones forming at high latitudes during polar air outbreaks. The associated high surface winds can be an important cause of coastal damage.They also seem to play a relevant role in the climate system by modulating the oceanic surface heat fluxes. This creates strong interest in understanding whether modern reanalysis datasets are able to represent polar lows, as well as how their representation may be sensitive to the model resolution. In this talk we investigate how ERA-Interim reanalysis represents the polar lows identified by the Norwegian meteorological services and listed in the STARS (Combination of Sea Surface Temperature and AltimeteR Synergy) dataset for the period 2002-2011. The sensitivity to resolution is explored by comparing ERA-Interim to the ECMWF operational analyses (2008-2011), which have three times higher horizontal resolution compared to ERA-Interim. We show that ERAI-Interim has excellent ability to capture the observed polar lows events with up to 90% of the observed events being found in the reanalysis. However, ERA-Interim tends to have polar lows of weaker dynamical intensity, in terms of both winds and vorticity, and with less spatial structure than in the ECMWF operational analyses (See Fig 1). Furthermore, we apply an objective feature tracking algorithm to the 3 hourly vorticity at 850 hPa with constraints on vorticity intensity and atmospheric static stability to objectively identify polar lows in the ERA-Interim reanalysis. We show that for the stronger polar lows the objective climatology shows good agreement with the STARS dataset over the 2002-2011 period. This allows us to extend the polar lows climatology over the whole ERA Interim period. Differences with another reanalysis product (NCEP-CFSR) will be also discussed. Fig 1: Composite of the tangential wind speed at 925 hPa for 34 polar lows observed in the Norwegian sea between 2008-2010 as represented by the ERA-Interim reanalysis (left) and by the ECMWF Operational analysis (right). Positive values indicate cyclonic circulation. The composite is centered on the polar low vorticity maxima and it is presented for a radial cap of 5 degrees of radius on the sphere (~550Km).

Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme.

PubMed

Salomón, Débora G; Fermento, María E; Gandini, Norberto A; Ferronato, María J; Arévalo, Julián; Blasco, Jorge; Andrés, Nancy C; Zenklusen, Jean C; Curino, Alejandro C; Facchinetti, María M

2014-05-01

Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1α, 25-dihydroxyvitamin D3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression.

Symptomatic treatment in multiple sclerosis-interim analysis of a nationwide registry.

PubMed

Skierlo, S; Rommer, P S; Zettl, U K

2017-04-01

To analyze symptomatic treatment in patients with multiple sclerosis (MS). Multiple sclerosis is a chronic inflammatory disease of the central nervous system, with accumulating disability symptoms like spasticity, voiding disorders, depression, and pain might occur. The nationwide German MS registry was initiated 2001 under guidance of the German MS society (Deutsche MS Gesellschaft). This study was performed as an interim analysis to lay foundation for future work on this topic. A subcohort of 5113 patients was assessed for this interim analysis. The mean age of the patients was 45.3 years; mean EDSS was 4.2. More than two-third of the enrolled patients were females (70.9%). Most frequent symptoms were fatigue (60%), followed by spasticity (52.5%) and voiding disorders (51.7%). The likelihood of treatment was highest for epileptic disorders (68.8%), spasticity (68.5%), pain (60.7%), and depression (58.9%). Multivariate regression analysis showed that retirement was the strongest factor predictive for antispastic treatment (β=.061, P=.005). Almost all patients in this analysis suffer from symptoms due to advanced MS. Treatment for the various symptoms differed tremendously. The likelihood of treatment correlated with the availability of effective therapeutic agents. Clinicians should put more awareness on MS symptoms. Symptomatic treatment may improve quality of life. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

76 FR 4369 - Interim Deputation Agreements; Interim BIA Adult Detention Facility Guidelines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... Adult Detention Facility Guidelines AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice. SUMMARY: This notice announces the online publication of the Interim BIA Adult Detention Facility Guidelines and... Indian Affairs Web site. DATES: These Interim BIA Adult Detention Facility Guidelines and Interim Model...

U.S. Policy Toward the Israeli-Egyptian Conflict September 1970-February 1972: The Analysis of a Failure of American Diplomacy.

DTIC Science & Technology

1983-12-01

opportunity existed in the Middle East for the conclusion of an interim settlement in the dispute between Egypt and Israel. Egyptian President Anwar el -Sadat...Richard M. Nixon; Henry A. Kissinger; William P. Rogers; Joseph Sisco; Donald Bergus; Michael Sterner; Golda Meir; Abba Eban; Moshe Dayan; Anwar el ...for the conclusion of an interim settlement in the dispute between Egypt and Israel. Egyptian President Anwar el -Sadat declared his willingness to

Evaluation and Analysis of SEASAT-A Scanning Multichannel Microwave Radiometer (SSMR) Antenna Pattern Correction (APC) Algorithm. Sub-task 4: Interim Mode T Sub B Versus Cross and Nominal Mode T Sub B

NASA Technical Reports Server (NTRS)

Kitzis, J. L.; Kitzis, S. N.

1979-01-01

The brightness temperature data produced by the SMMR Antenna Pattern Correction algorithm are evaluated. The evaluation consists of: (1) a direct comparison of the outputs of the interim, cross, and nominal APC modes; (2) a refinement of the previously determined cos beta estimates; and (3) a comparison of the world brightness temperature (T sub B) map with actual SMMR measurements.

Modeling Parenting Programs as an Interim Service for Families Waiting for Children's Mental Health Treatment.

PubMed

Cunningham, Charles E; Rimas, Heather; Chen, Yvonne; Deal, Ken; McGrath, Patrick; Lingley-Pottie, Patricia; Reid, Graham J; Lipman, Ellen; Corkum, Penny

2015-01-01

Using a discrete choice conjoint experiment, we explored the design of parenting programs as an interim strategy for families waiting for children's mental health treatment. Latent class analysis yielded 4 segments with different design preferences. Simulations predicted the Fast-Paced Personal Contact segment, 22.1% of the sample, would prefer weekly therapist-led parenting groups. The Moderate-Paced Personal Contact segment (24.7%) preferred twice-monthly therapist-led parenting groups with twice-monthly lessons. The Moderate-Paced E-Contact segment (36.3%), preferred weekly to twice-monthly contacts, e-mail networking, and a program combining therapist-led sessions with the support of a computerized telephone e-coach. The Slow-Paced E-Contact segment (16.9%) preferred an approach combining monthly therapist-led sessions, e-coaching, and e-mail networking with other parents. Simulations predicted 45.3% of parents would utilize an option combining 5 therapist coaching calls with 5 e-coaching calls, a model that could reduce costs and extend the availability of interim services. Although 41.0% preferred weekly pacing, 58% were predicted to choose an interim parenting service conducted at a twice-monthly to monthly pace. The results of this study suggest that developing interim services reflecting parental preferences requires a choice of formats that includes parenting groups, telephone-coached distance programs, and e-coaching options conducted at a flexible pace.

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

Energy policy act transportation study: Interim report on natural gas flows and rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-11-17

This report, Energy Policy Act Transportation Study: Interim Report on Natural Gas Flows and Rates, is the second in a series mandated by Title XIII, Section 1340, ``Establishment of Data Base and Study of Transportation Rates,`` of the Energy Policy Act of 1992 (P.L. 102--486). The first report Energy Policy Act Transportation Study: Availability of Data and Studies, was submitted to Congress in October 1993; it summarized data and studies that could be used to address the impact of legislative and regulatory actions on natural gas transportation rates and flow patterns. The current report presents an interim analysis of naturalmore » gas transportation rates and distribution patterns for the period from 1988 through 1994. A third and final report addressing the transportation rates and flows through 1997 is due to Congress in October 2000. This analysis relies on currently available data; no new data collection effort was undertaken. The need for the collection of additional data on transportation rates will be further addressed after this report, in consultation with the Congress, industry representatives, and in other public forums.« less

Flight set 360L007 (STS-33) insulation component. Volume 3: Final release

NASA Technical Reports Server (NTRS)

Hicken, Steve

1990-01-01

Volume 3 of this postfire report deals with the insulation component of the RSRM. The report is released twice for each flight set. The interim release contract date is on or before 60 days after the last field joint or nozzle to case joint is disassembled at KSC and contain the results of the KSC visual evaluation. The data contained in Volume 3 interim release supersedes the insulation data presented in the KSC 10 day report. The final release contract data is on or before 60 days after the last factory joint is disassembled at the Clearfield H-7 facility and contains the results of all visual evaluations and a thermal safety factor analysis. The data contained in the Volume 3 final release supersedes the interim release and the insulation data presented in the Clearfield 10 day report.

75 FR 984 - Draft Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

... Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites AGENCY... Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at Comprehensive Environmental Response... interim PRGs for dioxin in soil. These draft recommended interim PRGs were calculated using existing, peer...

Predicting clinical trial results based on announcements of interim analyses

PubMed Central

2014-01-01

Background Announcements of interim analyses of a clinical trial convey information about the results beyond the trial’s Data Safety Monitoring Board (DSMB). The amount of information conveyed may be minimal, but the fact that none of the trial’s stopping boundaries has been crossed implies that the experimental therapy is neither extremely effective nor hopeless. Predicting success of the ongoing trial is of interest to the trial’s sponsor, the medical community, pharmaceutical companies, and investors. We determine the probability of trial success by quantifying only the publicly available information from interim analyses of an ongoing trial. We illustrate our method in the context of the National Surgical Adjuvant Breast and Bowel (NSABP) trial, C-08. Methods We simulated trials based on the specifics of the NSABP C-08 protocol that were publicly available. We quantified the uncertainty around the treatment effect using prior weights for the various possibilities in light of other colon cancer studies and other studies of the investigational agent, bevacizumab. We considered alternative prior distributions. Results Subsequent to the trial’s third interim analysis, our predictive probabilities were: that the trial would eventually be successful, 48.0%; would stop for futility, 7.4%; and would continue to completion without statistical significance, 44.5%. The actual trial continued to completion without statistical significance. Conclusions Announcements of interim analyses provide information outside the DSMB’s sphere of confidentiality. This information is potentially helpful to clinical trial prognosticators. ‘Information leakage’ from standard interim analyses such as in NSABP C-08 is conventionally viewed as acceptable even though it may be quite revealing. Whether leakage from more aggressive types of adaptations is acceptable should be assessed at the design stage. PMID:24607270

Comparisons of the tropospheric specific humidity from GPS radio occultations with ERA-Interim, NASA MERRA, and AIRS data

NASA Astrophysics Data System (ADS)

Vergados, Panagiotis; Mannucci, Anthony J.; Ao, Chi O.; Verkhoglyadova, Olga; Iijima, Byron

2018-03-01

We construct a 9-year data record (2007-2015) of the tropospheric specific humidity using Global Positioning System radio occultation (GPS RO) observations from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission. This record covers the ±40° latitude belt and includes estimates of the zonally averaged monthly mean specific humidity from 700 up to 400 hPa. It includes three major climate zones: (a) the deep tropics (±15°), (b) the trade winds belts (±15-30°), and (c) the subtropics (±30-40°). We find that the RO observations agree very well with the European Centre for Medium-Range Weather Forecasts Re-Analysis Interim (ERA-Interim), the Modern-Era Retrospective Analysis for Research and Applications (MERRA), and the Atmospheric Infrared Sounder (AIRS) by capturing similar magnitudes and patterns of variability in the monthly zonal mean specific humidity and interannual anomaly over annual and interannual timescales. The JPL and UCAR specific humidity climatologies differ by less than 15 % (depending on location and pressure level), primarily due to differences in the retrieved refractivity. In the middle-to-upper troposphere, in all climate zones, JPL is the wettest of all data sets, AIRS is the driest of all data sets, and UCAR, ERA-Interim, and MERRA are in very good agreement, lying between the JPL and AIRS climatologies. In the lower-to-middle troposphere, we present a complex behavior of discrepancies, and we speculate that this might be due to convection and entrainment. Conclusively, the RO observations could potentially be used as a climate variable, but more thorough analysis is required to assess the structural uncertainty between centers and its origin.

IUS/TUG orbital operations and mission support study. Volume 2: Interim upper stage operations

NASA Technical Reports Server (NTRS)

1975-01-01

Background data and study results are presented for the interim upper stage (IUS) operations phase of the IUS/tug orbital operations study. The study was conducted to develop IUS operational concepts and an IUS baseline operations plan, and to provide cost estimates for IUS operations. The approach used was to compile and evaluate baseline concepts, definitions, and system, and to use that data as a basis for the IUS operations phase definition, analysis, and costing analysis. Both expendable and reusable IUS configurations were analyzed and two autonomy levels were specified for each configuration. Topics discussed include on-orbit operations and interfaces with the orbiter, the tracking and data relay satellites and ground station support capability analysis, and flight control center sizing to support the IUS operations.

Nucleic Acid-Based Nanoconstructs

Cancer.gov

Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

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

PubMed

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.

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

PubMed

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.

Pediatric glioblastoma multiforme: A single-institution experience.

PubMed

Ansari, Mansour; Nasrolahi, Hamid; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Ahmadloo, Niloofar; Omidvari, Shapour; Mosalaei, Ahmad

2012-07-01

Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But, it is rare in children. We report our experience on the pediatric population (20 years or younger) with GBM. Twenty-three patients with GBM who were treated at our hospital during 1990-2008 were evaluated. The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival was 16.0 months. Two cases survived more than 5 years. Age, radiation dose and performance status were significantly related to survival. GBM in pediatric patients were not very common in our center, and prognosis was unfavorable.

Role of Intra-operative MRI (iMRI) in Improving Extent of Resection and Survival in Patients with Glioblastoma Multiforme.

PubMed

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-07-01

Multiple intraoperative aids have been introduced to improve the extent of resection (EOR) in Glioblastoma Multiforme (GBM) patients, avoiding any new neurological deficits. Intraoperative MRI (iMRI) has been debated for its utility and cost for nearly two decades in neurosurgical literature. Review of literature suggests improved EOR in GBM patients who underwent iMRI assisted surgical resections leading to higher overall survival (OS) and progression free survival (PFS). iMRI provides real time intraoperative imaging with reasonable quality. Higher risk for new postoperative deficits with increased EOR is not reported in any study using iMRI. The level of evidence regarding prognostic benefits of iMRI is still of low quality..

[Toxic epidermal necrolysis associated with acute infection by Mycoplasma pneumoniae].

PubMed

Calvano, Roberta Amelia; Scacchi, María Florencia; Sojo, Magdalena María; Díaz, Silvia Marta; Volonteri, Victoria Inés; Giachetti, Ana Claudia

2013-01-01

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis represent different manifestations of the same spectrum of severe idiosyncratic cutaneous reactions to drugs and to a lesser extent are associated with infectous agents. Among these, Mycoplasma pneumoniae is one of the most frequent. We report the case of a female patient aged 5 years, with a toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection, which begins with a fever accompanied by a generalized rash with involvement of the mucous membranes. IgM serology for Mycoplasma pneumoniae was positive and initial biopsy was compatible with erythema multiforme major. The patient was treated with corticosteroids, intravenous immunoglobulin, plasmapheresis and strict care to prevent superinfection and sequels. After 31 days of hospitalization the patient was discharged from hospital.

Recurrent Glioblastoma Multiforme (grade IV - WHO 2007): a case of complete objective response - concomitant administration of Somatostatin / Octreotide, Retinoids, Vit E, Vit D3, Vit C, Melatonin, D2 R agonists (Di Bella Method.

PubMed

Di Bella, Giuseppe; Leci, Jovan; Ricchi, Alessandro; Toscano, Rosilde

2015-01-01

In a 41 year old man, with Glioblastoma Multiforme (Grade IV - WHO 2007) and loco-regional recurrence, treated conventionally with surgery, radio-therapy and Temolozomide, a complete objective response was subsequently achieved by means of the well-tolerated concomitant administration of Somatostatin + slow-release Octreotide, Melatonin, Retinoids solubilized in Vitamin E, Vit D3, Vit C, D2 R agonists, and Temolozomide. In addition to the positive and previously unreported therapeutic finding, this result allowed the patient to avoid further surgical trauma and the correlated risks, achieving an excellent quality of life and working capacity.

The use of group sequential, information-based sample size re-estimation in the design of the PRIMO study of chronic kidney disease.

PubMed

Pritchett, Yili; Jemiai, Yannis; Chang, Yuchiao; Bhan, Ishir; Agarwal, Rajiv; Zoccali, Carmine; Wanner, Christoph; Lloyd-Jones, Donald; Cannata-Andía, Jorge B; Thompson, Taylor; Appelbaum, Evan; Audhya, Paul; Andress, Dennis; Zhang, Wuyan; Solomon, Scott; Manning, Warren J; Thadhani, Ravi

2011-04-01

Chronic kidney disease is associated with a marked increase in risk for left ventricular hypertrophy and cardiovascular mortality compared with the general population. Therapy with vitamin D receptor activators has been linked with reduced mortality in chronic kidney disease and an improvement in left ventricular hypertrophy in animal studies. PRIMO (Paricalcitol capsules benefits in Renal failure Induced cardia MOrbidity) is a multinational, multicenter randomized controlled trial to assess the effects of paricalcitol (a selective vitamin D receptor activator) on mild to moderate left ventricular hypertrophy in patients with chronic kidney disease. Subjects with mild-moderate chronic kidney disease are randomized to paricalcitol or placebo after confirming left ventricular hypertrophy using a cardiac echocardiogram. Cardiac magnetic resonance imaging is then used to assess left ventricular mass index at baseline, 24 and 48 weeks, which is the primary efficacy endpoint of the study. Because of limited prior data to estimate sample size, a maximum information group sequential design with sample size re-estimation is implemented to allow sample size adjustment based on the nuisance parameter estimated using the interim data. An interim efficacy analysis is planned at a pre-specified time point conditioned on the status of enrollment. The decision to increase sample size depends on the observed treatment effect. A repeated measures analysis model, using available data at Week 24 and 48 with a backup model of an ANCOVA analyzing change from baseline to the final nonmissing observation, are pre-specified to evaluate the treatment effect. Gamma-family of spending function is employed to control family-wise Type I error rate as stopping for success is planned in the interim efficacy analysis. If enrollment is slower than anticipated, the smaller sample size used in the interim efficacy analysis and the greater percent of missing week 48 data might decrease the parameter estimation accuracy, either for the nuisance parameter or for the treatment effect, which might in turn affect the interim decision-making. The application of combining a group sequential design with a sample-size re-estimation in clinical trial design has the potential to improve efficiency and to increase the probability of trial success while ensuring integrity of the study.

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

Treatment outcome and prognostic factors of adult glioblastoma multiforme.

PubMed

Ahmadloo, Niloofar; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Nasrolahi, Hamid; Omidvari, Shapour; Mosalaei, Ahmad; Ansari, Mansour

2013-03-01

This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival. Copyright © 2012. Production and hosting by Elsevier B.V.

Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test.

PubMed

Hsueh, Eddy C; DeBloom, James R; Lee, Jonathan; Sussman, Jeffrey J; Covington, Kyle R; Middlebrook, Brooke; Johnson, Clare; Cook, Robert W; Slingluff, Craig L; McMasters, Kelly M

2017-08-29

A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS). Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18-87) and median Breslow thickness was 1.2 mm (range 0.2-12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each). Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01), while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis. Interim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP's ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients. ClinicalTrials.gov, NCT02355574  and NCT02355587.

Using phase II data for the analysis of phase III studies: An application in rare diseases.

PubMed

Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

2017-06-01

Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.

Flight Set 360T004 (STS-30) Insulation Component, Interim Release, Volume 3

NASA Technical Reports Server (NTRS)

Passman, James A.

1989-01-01

The insulation component of the Redesigned Solid Rocket Motor (RSRM) is discussed. The results of all visual evaluations and a thermal safety factor analysis are given. The data contained here supersedes the interim release and the insulation data presented in the Clearfield 10 day report. The objective is to document the postflight condition of the internal and external insulation of nozzle to case joints, the case field joints, the igniter to case joints, and the acreage insulation which made up RSRM-4A and RSRM-4B.

Interim Calibration Report for the SMMR Simulator

NASA Technical Reports Server (NTRS)

Gloersen, P.; Cavalieri, D.

1979-01-01

The calibration data obtained during the fall 1978 Nimbus-G underflight mission with the scanning multichannel microwave radiometer (SMMR) simulator on board the NASA CV-990 aircraft were analyzed and an interim calibration algorithm was developed. Data selected for the analysis consisted of in flight sky, first-year sea ice, and open water observations, as well as ground based observations of fixed targets with varied temperatures of selected instrument components. For most of the SMMR channels, a good fit to the selected data set was obtained with the algorithm.

R132H Mutation in IDH1 Gene is Associated with Increased Tumor HIF1-Alpha and Serum VEGF Levels in Primary Glioblastoma Multiforme.

PubMed

Yalaza, Cem; Ak, Handan; Cagli, Mehmet Sedat; Ozgiray, Erkin; Atay, Sevcan; Aydin, Hikmet Hakan

2017-05-01

Glioblastoma multiforme (GBM) is the most common form of primary brain tumors. Although mutations in isocitrate dehydrogenase-1 (IDH1) have been identified in a number of cancers, their role in tumor development has not been fully elucidated. In this study, we aimed to investigate the association between IDH1 mutations, tumor tissue HIF-1 alpha, and serum VEGF levels in patients with primary GBM for the first time. 32 patients (mean age, years: 58±14.0) diagnosed with primary glioblastoma multiforme were screened for IDH1 mutations (R132H, R132S, R132C and R132L) by direct sequencing. Serum VEGF and tumor tissue HIF1-alpha levels were measured by enzyme-linked immunosorbent assay. Associations between categoric variables were determined using chi-square tests. Differences between two groups were compared with t test for continuous variables. Six percent of patients were found to be heterozygous for R132H mutation. Tumor HIF1-alpha and serum VEGF levels were found to be significantly increased in IDH1 -mutated tumor tissues ( p <0.0001 and p =0.0454, respectively). Our results suggest that mutated IDH1 may contribute to carcinogenesis via induction of HIF-1 alpha pathway in primary GBM. © 2017 by the Association of Clinical Scientists, Inc.

IVHS Countermeasures for Rear-End Collision, Task 1 Vol. V: 1985 NASS Case Analysis

DOT National Transportation Integrated Search

1994-02-15

The Task 1 Interim Report consists of six volumes. This Volume, Volume V, 1985 NASS Analysis, presents the results of the analysis of the 1985 NASS crash data. Data from 1985 was selected for analysis because it provided more insight into roadway var...

5 CFR 772.102 - Interim personnel actions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Interim personnel actions. 772.102 Section 772.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.102 Interim personnel actions. When an employee or...

5 CFR 772.102 - Interim personnel actions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interim personnel actions. 772.102 Section 772.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.102 Interim personnel actions. When an employee or...

Certification and verification for Northrup model NSC-01-0732 fresnel lens concentrating solar collector

NASA Technical Reports Server (NTRS)

1979-01-01

Structural analysis and certification of the collector system is presented. System verification against the interim performance criteria is presented and indicated by matrices. The verification discussion, analysis, and test results are also given.

Innovations for Evaluation Research: Multiform Protocols, Visual Analog Scaling, and the Retrospective Pretest-Posttest Design.

PubMed

Chang, Rong; Little, Todd D

2018-06-01

In this article, we review three innovative methods: multiform protocols, visual analog scaling, and the retrospective pretest-posttest design that can be used in evaluation research. These three techniques have been proposed for decades, but unfortunately, they are still not utilized readily in evaluation research. Our goal is to familiarize researchers with these underutilized research techniques that could reduce personnel effort and costs for data collection while producing better inferences for a study. We begin by discussing their applications and special unique features. We then discuss each technique's strengths and limitations and offer practical tips on how to better implement these methods in evaluation research. We then showcase two recent empirical studies that implement these methods in real-world evaluation research applications.

In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

NASA Astrophysics Data System (ADS)

Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

2008-11-01

The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

Glioblastoma multiforme of the cerebellum: description of three cases.

PubMed

Luccarelli, G

1980-01-01

Only 43 cases of glioblastoma multiforme of the cerebellum have been reported in the literature. This report is based on the findings of 3 cerebellar glioblastomas in a review of 1,206 consecutive confirmed cases of glioblastoma operated on between 1947 and 1977 at the Istituto Neurologico of Milan, giving an incidence of 0.24%. Clinical features are similar to those of any other fast-growing subtentorial tumour. Neuroradiological studies, including CAT, are of little help in predicting the exact nature of these tumours before surgery. A correct diagnosis can be reached only by microscopic examination. Histological patterns appear in no way to differ from those of cerebral glioblastoma. The biological behaviour of these tumours is in all respects identical to that of glioblastoma of cerebral hemispheres.

Pediatric glioblastoma multiforme: A single-institution experience

PubMed Central

Ansari, Mansour; Nasrolahi, Hamid; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Ahmadloo, Niloofar; Omidvari, Shapour; Mosalaei, Ahmad

2012-01-01

Background: Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But, it is rare in children. We report our experience on the pediatric population (20 years or younger) with GBM. Patients and Methods: Twenty-three patients with GBM who were treated at our hospital during 1990–2008 were evaluated. Results: The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival was 16.0 months. Two cases survived more than 5 years. Age, radiation dose and performance status were significantly related to survival. Conclusion: GBM in pediatric patients were not very common in our center, and prognosis was unfavorable. PMID:23248421

Cyclophilin B Supports Myc and Mutant p53 Dependent Survival of Glioblastoma Multiforme Cells

PubMed Central

Choi, Jae Won; Schroeder, Mark A.; Sarkaria, Jann N.; Bram, Richard J.

2014-01-01

Glioblastoma multiforme (GBM) is an aggressive, treatment-refractory type of brain tumor for which effective therapeutic targets remain important to identify. Here we report that cyclophilin B (CypB), a prolyl isomerase residing in the endoplasmic reticulum (ER), provides an essential survival signal in GBM cells. Analysis of gene expression databases revealed that CypB is upregulated in many cases of malignant glioma. We found that suppression of CypB reduced cell proliferation and survival in human GBM cells in vitro and in vivo. We also found that treatment with small molecule inhibitors of cyclophilins, including the approved drug cyclosporine, greatly reduced the viability of GBM cells. Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS-MAPK pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1 and JAK/STAT3 signaling. Elevated reactive oxygen species, ER expansion and abnormal unfolded protein responses in CypB-depleted GBM cells indicated that CypB alleviates oxidative and ER stresses and coordinates stress adaptation responses. Enhanced cell survival and sustained expression of multiple oncogenic proteins downstream of CypB may thus contribute to the poor outcome of GBM tumors. Our findings link chaperone-mediated protein folding in the ER to mechanisms underlying oncogenic transformation, and they make CypB an attractive and immediately targetable molecule for GBM therapy. PMID:24272483

Interim Expertise

ERIC Educational Resources Information Center

Anyaso, Hilary Hurd

2009-01-01

The Registry for College and University Presidents places former executives in interim presidential and other senior-level posts and is familiar with the challenges interim executives and institutions encounter in times of leadership transitions. However, the one big advantage interims bring to institutions, says Registry Vice President Kevin J.…

40 CFR 155.56 - Interim registration review decision.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Interim registration review decision... PROGRAMS REGISTRATION STANDARDS AND REGISTRATION REVIEW Registration Review Procedures § 155.56 Interim registration review decision. The Agency may issue, when it determines it to be appropriate, an interim...

17 CFR 210.8-03 - Interim financial statements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (§ 249.308(a) of this chapter) must be reviewed by an independent public accountant using professional... interim financial statements have been reviewed by an independent public accountant, a report of the accountant on the review must be filed with the interim financial statements. Interim financial statements...

24 CFR 35.1330 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.1330 Section... Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1330 Interim controls. Interim controls of lead-based paint hazards identified in a risk assessment shall be conducted in accordance with...

7 CFR 1738.21 - Interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1738.21 Section 1738.21... Interim financing. (a) Upon notification by RUS that an applicant's application is considered complete, the applicant may enter into an interim financing agreement with a lender other than RUS or use its...

An Approach for Evaluating the Technical Quality of Interim Assessments

ERIC Educational Resources Information Center

Li, Ying; Marion, Scott; Perie, Marianne; Gong, Brian

2010-01-01

Increasing numbers of schools and districts have expressed interest in interim assessment systems to prepare for summative assessments and to improve teaching and learning. However, with so many commercial interim assessments available, schools and districts are struggling to determine which interim assessment is most appropriate to their needs.…

47 CFR 51.611 - Interim wholesale rates.

Code of Federal Regulations, 2010 CFR

2010-10-01

... selecting a particular discount rate. The same discount percentage rate shall be used to establish interim... 47 Telecommunication 3 2010-10-01 2010-10-01 false Interim wholesale rates. 51.611 Section 51.611... Resale § 51.611 Interim wholesale rates. (a) If a state commission cannot, based on the information...

7 CFR 15a.71 - Interim procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Interim procedures. 15a.71 Section 15a.71 Agriculture Office of the Secretary of Agriculture EDUCATION PROGRAMS OR ACTIVITIES RECEIVING OR BENEFITTING FROM FEDERAL FINANCIAL ASSISTANCE Procedures (Interim) § 15a.71 Interim procedures. For the purposes of...

77 FR 55230 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-01; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0068] Japan Lessons-Learned Project Directorate Interim... Commission (NRC). ACTION: Japan Lessons-Learned Project Directorate interim staff guidance; issuance. SUMMARY...-Learned Project Directorate Interim Staff Guidance (JLD-ISG), JLD-ISG-2012-01, ``Compliance with Order EA...

77 FR 55231 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-02; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0069] Japan Lessons-Learned Project Directorate Interim...-Learned Project Directorate interim staff guidance; issuance. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing the Final Japan Lessons-Learned Project Directorate Interim...

7 CFR 1735.75 - Interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1735.75 Section 1735.75... Involving Loan Funds § 1735.75 Interim financing. (a) A borrower may submit a written request for RUS approval of interim financing if it is necessary to close an acquisition before the loan to finance the...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2014 CFR

2014-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2013 CFR

2013-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2012 CFR

2012-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2011 CFR

2011-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting.

PubMed

Dal-Ré, Rafael; Ross, Joseph S; Marušić, Ana

2016-07-01

To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. Copyright © 2016 Elsevier Inc. All rights reserved.

Engagement of Patients With Advanced Cancer

ClinicalTrials.gov

2017-05-12

End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

ClinicalTrials.gov

2018-03-07

Pilomyxoid Astrocytoma; Pilocytic Astrocytoma; Glioma, Astrocytic; Optic Nerve Glioma; Pleomorphic Xanthoastrocytoma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma; DIPG; Low-grade Glioma; Brainstem Glioma

Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

ClinicalTrials.gov

2018-01-26

Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

75 FR 13610 - Office of New Reactors; Interim Staff Guidance on Implementation of a Seismic Margin Analysis for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... Staff Guidance on Implementation of a Seismic Margin Analysis for New Reactors Based on Probabilistic... Seismic Margin Analysis for New Reactors Based on Probabilistic Risk Assessment,'' (Agencywide Documents.../COL-ISG-020 ``Implementation of a Seismic Margin Analysis for New Reactors Based on Probabilistic Risk...

Comparative Analysis of Languages for Machine Processing. Interim Report.

ERIC Educational Resources Information Center

Zierer, Ernesto; And Others

This report gives the results obtained in the semantic and syntactic analysis of the Japanese particles "de,""ni,""e," and "wo" in comparison to their equivalents in English, German, and Spanish. The study is based on the so-called "Correlational Analysis" as proposed by Ernst von Glaserfeld. The…

The role of the Data and Safety Monitoring Board in a clinical trial: The CRISIS Study

PubMed Central

Holubkov, Richard; Casper, T. Charles; Dean, J. Michael; Anand, K. J. S.; Zimmerman, Jerry; Meert, Kathleen L.; Newth, Christopher J. L.; Berger, John; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

2012-01-01

Objective Randomized clinical trials are commonly overseen by a data and safety monitoring board (DSMB) comprised of experts in medicine, ethics, and biostatistics. DSMB responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. DSMB decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate DSMB oversight into the design, monitoring, and reporting of randomized trials. Design Case study, narrative review. Methods The DSMB’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. Findings The NIH-appointed CRISIS DSMB was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested DSMB interim review before opening CRISIS to children below one year of age. The first interim analysis found higher 28-day mortality in one treatment arm. The DSMB maintained trial closure to younger children, and requested a second interim data review six months later. At this second meeting, mortality was no longer of concern, while a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the DSMB elected to examine conditional power, and unmask treatment arm identities. Upon finding somewhat greater efficacy in the placebo arm, the DSMB recommended stopping CRISIS due to futility. Conclusions The design and operating procedures of a multicenter randomized trial must consider a pivotal DSMB role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The DSMB must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups. PMID:23392377

Data Analysis of GPM Constellation Satellites-IMERG and ERA-Interim precipitation products over West of Iran

NASA Astrophysics Data System (ADS)

Sharifi, Ehsan; Steinacker, Reinhold; Saghafian, Bahram

2016-04-01

Precipitation is a critical component of the Earth's hydrological cycle. The primary requirement in precipitation measurement is to know where and how much precipitation is falling at any given time. Especially in data sparse regions with insufficient radar coverage, satellite information can provide a spatial and temporal context. Nonetheless, evaluation of satellite precipitation is essential prior to operational use. This is why many previous studies are devoted to the validation of satellite estimation. Accurate quantitative precipitation estimation over mountainous basins is of great importance because of their susceptibility to hazards. In situ observations over mountainous areas are mostly limited, but currently available satellite precipitation products can potentially provide the precipitation estimation needed for meteorological and hydrological applications. One of the newest and blended methods that use multi-satellites and multi-sensors has been developed for estimating global precipitation. The considered data set known as Integrated Multi-satellitE Retrievals (IMERG) for GPM (Global Precipitation Measurement) is routinely produced by the GPM constellation satellites. Moreover, recent efforts have been put into the improvement of the precipitation products derived from reanalysis systems, which has led to significant progress. One of the best and a worldwide used model is developed by the European Centre for Medium Range Weather Forecasts (ECMWF). They have produced global reanalysis daily precipitation, known as ERA-Interim. This study has evaluated one year of precipitation data from the GPM-IMERG and ERA-Interim reanalysis daily time series over West of Iran. IMERG and ERA-Interim yield underestimate the observed values while IMERG underestimated slightly and performed better when precipitation is greater than 10mm. Furthermore, with respect to evaluation of probability of detection (POD), threat score (TS), false alarm ratio (FAR) and probability of false detection (POFD) IMERG yields a better value of POD, TS, FAR and POFD in comparison to era-Interim. Overall, ERA-Interim product produced fewer robust results when compared to IMERG.

MUC-4 Test Results and Analysis

DTIC Science & Technology

1992-01-01

PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 MUC3 MUC4 STEMS 15,285 INFLECTED FORMS 14,56 1 TOTALS est at 10,000...34 . As an indication of system development during MUC4 , we can compare our TST3 results with our results on th e MUC-4 interim test (TST2) . The relevant... MUC4 Interim Test) Summary Scores SLOT POS ACT COR PAR INC ICR IPA SPU MIS NON REC PRE OVG inc-total 529 1189 160 63 24 0 23 942 282 718 36 16 79 perp

First Aid: Rashes

MedlinePlus

... for: Parents Kids Teens First Aid: Skin Infections Poison Ivy Erythema Multiforme Hives (Urticaria) Erythema Toxicum Eczema Pityriasis ... Fifth Disease Shingles Diaper Rash Word Find: Skin Poison Ivy Rashes: The Itchy Truth Your Skin Impetigo Ringworm ...

12 CFR 552.2-2 - Procedures for organization of interim Federal stock association.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Procedures for organization of interim Federal stock association. (a) Applications for permission to organize... chapter or § 552.2-1(b)(3) of this part. (b) Approval of an application for permission to organize an... the interim was chartered to facilitate. Applications for permission to organize an interim Federal...

Detailed Skylab ECS consumables analysis for the interim revision flight plan (November, 1972, SL-1 launch)

NASA Technical Reports Server (NTRS)

Wells, C.; Kolkhorst, H. E.

1971-01-01

The consumables analysis was performed for the Skylab 2, 3, and 4 Preliminary Reference Interim Revision Flight Plan. The analysis and the results are based on the mission requirements as specified in the flight plan and on other available data. The results indicate that the consumables requirements for the Skylab missions allow for remaining margins (percent) of oxygen, nitrogen, and water nominal as follows: 83.5, 90.8, and 88.7 for mission SL-2; 57.1, 64.1, and 67.3 for SL-3; and 30.8, 44.3, and 46.5 for SL-4. Performance of experiment M509 as scheduled in the flight plan results in venting overboard the cluster atmosphere. This is due to the addition of nitrogen for propulsion and to the additional oxygen introduced into the cabin when the experiment is performed with the crewman suited.

Impact evaluation of Morgantown PRT 1975-1976 ridership: Interim Analysis

DOT National Transportation Integrated Search

1977-06-01

An analysis of the ridership levels of the Morgantown PRT system during its : initial period of operation, the 1975-1976 academic year, is presented. PRT ridership : by day, weekly ridership trends in terms of exogeneous events, the influence of : fe...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

Interim analysis report : model deployment of a regional, multi-modal 511 traveler information system

DOT National Transportation Integrated Search

2004-02-17

This document presents the results of the analysis of baseline, or "pre-enhancement," data describing the operation of the existing 511 telephone traveler information system operated by the Arizona Department of Transportation (ADOT). The model deplo...

Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

PubMed

Chang, Susan M; Barker, Fred G

2005-11-01

Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

Genome-Wide Methylation Analyses in Glioblastoma Multiforme

PubMed Central

Lai, Rose K.; Chen, Yanwen; Guan, Xiaowei; Nousome, Darryl; Sharma, Charu; Canoll, Peter; Bruce, Jeffrey; Sloan, Andrew E.; Cortes, Etty; Vonsattel, Jean-Paul; Su, Tao; Delgado-Cruzata, Lissette; Gurvich, Irina; Santella, Regina M.; Ostrom, Quinn; Lee, Annette; Gregersen, Peter; Barnholtz-Sloan, Jill

2014-01-01

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery and validation datasets. Global methylation levels were assessed by analysis of L1 retrotransposon (LINE1), 5 methyl-deoxycytidine (5m-dC) and 5 hydroxylmethyl-deoxycytidine (5hm-dC) in the discovery dataset. We validated a total of 1548 CpG sites (1307 genes) that were differentially methylated in GBM compared to controls. There were more than twice as many hypomethylated genes as hypermethylated ones. Both the discovery and validation datasets found 5 tumor methylation classes. Pathway analyses showed that the top ten pathways in hypomethylated genes were all related to functions of innate and acquired immunities. Among hypermethylated pathways, transcriptional regulatory network in embryonic stem cells was the most significant. In the study of global methylation markers, 5m-dC level was the best discriminant among methylation classes, whereas in survival analyses, high level of LINE1 methylation was an independent, favorable prognostic factor in the discovery dataset. Based on a pathway approach, hypermethylation in genes that control stem cell differentiation were significant, poor prognostic factors of overall survival in both the discovery and validation datasets. Approaches that targeted these methylated genes may be a future therapeutic goal. PMID:24586730

The evolution of the EGFRvIII (rindopepimut) immunotherapy for glioblastoma multiforme patients.

PubMed

Paff, Michelle; Alexandru-Abrams, Daniela; Hsu, Frank P K; Bota, Daniela A

2014-01-01

Glioblastoma Multiforme (GBM) is the most common type of brain tumor and it is uniformly fatal. The community standard of treatment for this disease is gross or subtotal resection of the tumor, followed by radiation and temozolomide. At recurrence bevacizumab can be added for increased progression free survival. Many challenges are encountered while trying to devise new drugs to treat GBM, such as the presence of the blood brain barrier which is impermeable to most drugs. Therefore in the past few years attention was turned to immunological means for the treatment of this devastating disease. EGFRvIII targeting has proven a good way to attack glioblastoma cells by using the immune system. Although in still in development, this approach holds the promise as a great first step toward immune-tailored drugs for the treatment of brain cancers.

Models of comorbidity for multifactorial disorders.

PubMed Central

Neale, M C; Kendler, K S

1995-01-01

We develop several formal models for comorbidity between multifactorial disorders. Based on the work of D. N. Klein and L. P. Riso, the models include (i) alternate forms, where the two disorders have the same underlying continuum of liability; (ii) random multiformity, in which affection status on one disorder abruptly increases risk for the second; (iii) extreme multiformity, where only extreme cases have an abruptly increased risk for the second disorder; (iv) three independent disorders, in which excess comorbid cases are due to a separate, third disorder; (v) correlated liabilities, where the risk factors for the two disorders correlate; and (vi) direct causal models, where the liability for one disorder is a cause of the other disorder. These models are used to make quantitative predictions about the relative proportions of pairs of relatives who are classified according to whether each relative has neither disorder, disorder A but not B, disorder B but not A, or both A and B. For illustration, we analyze data on major depression (MD) and generalized anxiety disorder (GAD) assessed in adult female MZ and DZ twins, which enable estimation of the relative impact of genetic and environmental factors. Several models are rejected--that comorbid cases are due to chance; multiformity of GAD; a third independent disorder; and GAD being a cause of MD. Of the models that fit the data, correlated liabilities, MD causes GAD, and reciprocal causation seem best. MD appears to be a source of liability for GAD. Possible extensions to the models are discussed. PMID:7573055

Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study.

PubMed

Arzimanoglou, Alexis; Ferreira, Jose A; Satlin, Andrew; Mendes, Shannon; Williams, Betsy; Critchley, David; Schuck, Edgar; Hussein, Ziad; Kumar, Dinesh; Dhadda, Shobha; Bibbiani, Francesco

2016-05-01

A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects ≥ 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs. Interim safety results showed that treatment-emergent adverse events (TEAEs) were similar between the rufinamide (22 [88.0%]) and any-other-AED group (9 [81.8%]), with most events considered mild or moderate. A population PK analysis was conducted including plasma rufinamide concentrations from Study 303 and two other study populations of LGS subjects ≥ 4 years. The rufinamide PK profile was dose independent. The apparent clearance (CL/F) estimated from the PK model was 2.19 L/h; it was found to increase significantly as a function of body weight. Coadministration of valproic acid significantly decreased rufinamide CL/F. CL/F was not significantly affected by other concomitant AEDs, age, gender, race, hepatic function, or renal function. No adjustments to body weight-based rufinamide dosing in subjects ≥ 1 to < 4 years are necessary. Rufinamide was safe and well tolerated in these pediatric subjects. Results from the interim analysis demonstrate that rufinamide's safety and PK profile is comparable in subjects ≥ 1 to < 4 and ≥ 4 years with LGS. Study 303 (clinicaltrials.gov: NCT01405053). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

76 FR 14559 - Federal Acquisition Regulation; Justification and Approval of Sole-Source 8(a) Contracts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Space Administration (NASA). ACTION: Interim rule. SUMMARY: DoD, GSA, and NASA are issuing an interim..., and NASA are issuing an interim rule amending the FAR, to implement section 811 of the National... meetings, DoD, GSA, and NASA weighed the costs and benefits of publishing this rule as proposed or interim...

Interim Administrators in Higher Education: A National Study

ERIC Educational Resources Information Center

Huff, Marie Thielke; Neubrander, Judy

2015-01-01

The focus of this paper is on the roles and experiences of interim administrators in higher education. A survey was given to current and recent interim administrators in four-year public universities and colleges across the United States. The goals were to identify the advantages and disadvantages of using and serving as interims, and to solicit…

Interim Draft: Biological Sampling and Analysis Plan Outline ...

EPA Pesticide Factsheets

Standard Operation Procedures This interim sampling and analysis plan (SAP) outline was developed specifically as an outline of the output that will be generated by a developing on-line tool called the MicroSAP. The goal of the MicroSAP tool is to assist users with development of SAPs needed for site characterization, verification sampling, and post decontamination sampling stages of biological sampling and analysis activities in which the EPA would be responsible for conducting sampling. These activities could include sampling and analysis for a biological contamination incident, a research study, or an exercise. The development of this SAP outline did not consider the initial response of an incident, as it is assumed that the initial response would have been previously completed by another agency during the response, or the clearance phase, as it is assumed that separate committee would be established to make decisions regarding clearing a site. This outline also includes considerations for capturing the associated data quality objectives in the SAP.

RESEARCH METHOD FOR SAMPLING AND ANALYSIS OF FIBROUS AMPHIBOLE IN VERMICULITE ATTIC INSULATION

EPA Science Inventory

NRMRL hosted a meeting on July 17-18, 2003 entitled, "Analytical Method for Bulk Analysis of Vermiculite." The purpose of this effort was to produce an interim research method for use by U.S. EPA's Office of Research and Development (ORD) for the analysis of bulk vermiculite for...

78 FR 8295 - Guarantees for Bonds Issued for Community or Economic Development Purposes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

.... V. Rulemaking Analysis A. Executive Order (E.O.) 12866; Regulatory Impact Analysis It has been... Budget. The Regulatory Impact Analysis prepared by the CDFI Fund for the interim rule is provided below... Community Investment Impact System (CIIS), which collects data from CDFIs that have received awards from the...

Putting TCGA Data to Work - TCGA

Cancer.gov

Neurosurgeon Cameron Brennan of Memorial Sloan-Kettering Cancer Center used TCGA data to define subgroups of patients with a deadly brain cancer called glioblastoma multiforme. Learn more about his research in this TCGA in Action case study.

Side Effects of HIV Medicines: HIV and Rash

MedlinePlus

... swallowing, dizziness or lightheadedness, and kidney damage. Stevens-Johnson syndrome (SJS) (also called erythema multiforme major) is ... National Center for Advancing Translational Sciences (NCATS): Stevens-Johnson syndrome Print This Fact Sheet Entire Series Related ...

Adaptive graph-based multiple testing procedures

PubMed Central

Klinglmueller, Florian; Posch, Martin; Koenig, Franz

2016-01-01

Multiple testing procedures defined by directed, weighted graphs have recently been proposed as an intuitive visual tool for constructing multiple testing strategies that reflect the often complex contextual relations between hypotheses in clinical trials. Many well-known sequentially rejective tests, such as (parallel) gatekeeping tests or hierarchical testing procedures are special cases of the graph based tests. We generalize these graph-based multiple testing procedures to adaptive trial designs with an interim analysis. These designs permit mid-trial design modifications based on unblinded interim data as well as external information, while providing strong family wise error rate control. To maintain the familywise error rate, it is not required to prespecify the adaption rule in detail. Because the adaptive test does not require knowledge of the multivariate distribution of test statistics, it is applicable in a wide range of scenarios including trials with multiple treatment comparisons, endpoints or subgroups, or combinations thereof. Examples of adaptations are dropping of treatment arms, selection of subpopulations, and sample size reassessment. If, in the interim analysis, it is decided to continue the trial as planned, the adaptive test reduces to the originally planned multiple testing procedure. Only if adaptations are actually implemented, an adjusted test needs to be applied. The procedure is illustrated with a case study and its operating characteristics are investigated by simulations. PMID:25319733

Interim analyses in 2 x 2 crossover trials.

PubMed

Cook, R J

1995-09-01

A method is presented for performing interim analyses in long term 2 x 2 crossover trials with serial patient entry. The analyses are based on a linear statistic that combines data from individuals observed for one treatment period with data from individuals observed for both periods. The coefficients in this linear combination can be chosen quite arbitrarily, but we focus on variance-based weights to maximize power for tests regarding direct treatment effects. The type I error rate of this procedure is controlled by utilizing the joint distribution of the linear statistics over analysis stages. Methods for performing power and sample size calculations are indicated. A two-stage sequential design involving simultaneous patient entry and a single between-period interim analysis is considered in detail. The power and average number of measurements required for this design are compared to those of the usual crossover trial. The results indicate that, while there is minimal loss in power relative to the usual crossover design in the absence of differential carry-over effects, the proposed design can have substantially greater power when differential carry-over effects are present. The two-stage crossover design can also lead to more economical studies in terms of the expected number of measurements required, due to the potential for early stopping. Attention is directed toward normally distributed responses.

On the comparisons of tropical relative humidity in the lower and middle troposphere among COSMIC radio occultations and MERRA and ECMWF data sets

NASA Astrophysics Data System (ADS)

Vergados, P.; Mannucci, A. J.; Ao, C. O.; Jiang, J. H.; Su, H.

2015-04-01

The spatial variability of the tropical tropospheric relative humidity (RH) throughout the vertical extent of the troposphere is examined using Global Positioning System Radio Occultation (GPSRO) observations from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission. These high vertical resolution observations capture the detailed structure and moisture budget of the Hadley Cell circulation. We compare the COSMIC observations with the European Center for Medium-range Weather Forecast (ECMWF) Reanalysis Interim (ERA-Interim) and the Modern-Era Retrospective analysis for Research and Applications (MERRA) climatologies. Qualitatively, the spatial pattern of RH in all data sets matches up remarkably well, capturing distinct features of the general circulation. However, RH discrepancies exist between ERA-Interim and COSMIC data sets that are noticeable across the tropical boundary layer. Specifically, ERA-Interim shows a drier Intertropical Convergence Zone (ITCZ) by 15-20% compared to both COSMIC and MERRA data sets, but this difference decreases with altitude. Unlike ECMWF, MERRA shows an excellent agreement with the COSMIC observations except above 400 hPa, where GPSRO observations capture drier air by 5-10%. RH climatologies were also used to evaluate intraseasonal variability. The results indicate that the tropical middle troposphere at ±5-25° is most sensitive to seasonal variations. COSMIC and MERRA data sets capture the same magnitude of the seasonal variability, but ERA-Interim shows a weaker seasonal fluctuation up to 10% in the middle troposphere inside the dry air subsidence regions of the Hadley Cell. Over the ITCZ, RH varies by maximum 9% between winter and summer.

IVHS Countermeasures for Rear-End Collisions, Task 1 Vol. III: 1991 NASS CDS Case Analysis

DOT National Transportation Integrated Search

1994-02-15

This report is from the NHTSA sponsored program, "IVHS Countermeasures for Rear-End Collisions". The Task 1 Interim Report consists of six volumes. This Volume, Volume III, 1991 NASS CDS Clinical Case Analysis presents the results of a clinical case ...

42 CFR 418.307 - Periodic interim payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) MEDICARE PROGRAM HOSPICE CARE Payment for Hospice Care § 418.307 Periodic interim payments... payments. The biweekly interim payment amount is based on the total estimated Medicare payments for the...

Predicting epidermal growth factor receptor gene amplification status in glioblastoma multiforme by quantitative enhancement and necrosis features deriving from conventional magnetic resonance imaging.

PubMed

Dong, Fei; Zeng, Qiang; Jiang, Biao; Yu, Xinfeng; Wang, Weiwei; Xu, Jingjing; Yu, Jinna; Li, Qian; Zhang, Minming

2018-05-01

To study whether some of the quantitative enhancement and necrosis features in preoperative conventional MRI (cMRI) had a predictive value for epidermal growth factor receptor (EGFR) gene amplification status in glioblastoma multiforme (GBM).Fifty-five patients with pathologically determined GBMs who underwent cMRI were retrospectively reviewed. The following cMRI features were quantitatively measured and recorded: long and short diameters of the enhanced portion (LDE and SDE), maximum and minimum thickness of the enhanced portion (MaxTE and MinTE), and long and short diameters of the necrotic portion (LDN and SDN). Univariate analysis of each feature and a decision tree model fed with all the features were performed. Area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the performance of features, and predictive accuracy was used to assess the performance of the model.For single feature, MinTE showed the best performance in differentiating EGFR gene amplification negative (wild-type) (nEGFR) GBM from EGFR gene amplification positive (pEGFR) GBM, and it got an AUC of 0.68 with a cut-off value of 2.6 mm. The decision tree model included 2 features MinTE and SDN, and got an accuracy of 0.83 in validation dataset.Our results suggest that quantitative measurement of the features MinTE and SDN in preoperative cMRI had a high accuracy for predicting EGFR gene amplification status in GBM.

Long non-coding RNA CASP5 promotes the malignant phenotypes of human glioblastoma multiforme.

PubMed

Zhou, Yali; Dai, Wei; Wang, Handong; Pan, Hao; Wang, Qiang

2018-06-12

Long non-coding RNAs (lncRNAs) have been demonstrated to be intensively involved in the development of various carcinomas, including glioblastoma multiforme (GBM). However, only a few of them have been well characterized. LncRNA CASP5 have been found to be up-regulated in GBM tissues compared with normal tissues in a microarray-based lncRNA profiling study. In the present study, we further explored the biological role of lncRNA CASP5 in GBM. We examined the expression level of lncRNA CASP5 in GBM tissues as well as GBM cell lines. CCK-8 assay, flow cytometric analysis, western blotting, orthotopic GBM model as well as transwell assay were performed to investigate the biological role of CASP5. We observed that lncRNA CASP5 was highly expressed in GBM tissues and cell lines. Knockdown of CASP5 greatly inhibited GBM proliferation and resulted in G1 cell cycle arrest along with higher apoptosis ratios in vitro and in vivo, while overexpression led to the opposite phenomenon. Furthermore, the migration and invasion ability of GBM cells were significantly decreased after CASP5 down-regulation, while increased migration and invasion can be observed after CASP5 up-regulation. We demonstrate for the first time the potential oncogenic role of lncRNA CASP5 which may be helpful for identifying novel therapeutic targets in GBM. Copyright © 2018 Elsevier Inc. All rights reserved.

Epstein–Barr Virus in Gliomas: Cause, Association, or Artifact?

PubMed Central

Akhtar, Saghir; Vranic, Semir; Cyprian, Farhan Sachal; Al Moustafa, Ala-Eddin

2018-01-01

Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM) is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein–Barr virus (EBV) that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever) and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS) lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s), glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors. PMID:29732319

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PubMed

Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

2005-12-20

We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme.

PubMed

Vidone, Michele; Clima, Rosanna; Santorsola, Mariangela; Calabrese, Claudia; Girolimetti, Giulia; Kurelac, Ivana; Amato, Laura Benedetta; Iommarini, Luisa; Trevisan, Elisa; Leone, Marco; Soffietti, Riccardo; Morra, Isabella; Faccani, Giuliano; Attimonelli, Marcella; Porcelli, Anna Maria; Gasparre, Giuseppe

2015-06-01

Glioblastoma multiforme (GBM) is the most malignant brain cancer in adults, with a poor prognosis, whose molecular stratification still represents a challenge in pathology and clinics. On the other hand, mitochondrial DNA (mtDNA) mutations have been found in most tumors as modifiers of the bioenergetics state, albeit in GBM a characterization of the mtDNA status is lacking to date. Here, a characterization of the burden of mtDNA mutations in GBM samples was performed. First, investigation of tumor-specific vs. non tumor-specific mutations was carried out with the MToolBox bioinformatics pipeline by analyzing 45 matched tumor/blood samples, from whole genome or whole exome sequencing datasets obtained from The Cancer Genome Atlas (TCGA) consortium. Additionally, the entire mtDNA sequence was obtained in a dataset of 104 fresh-frozen GBM samples. Mitochondrial mutations with potential pathogenic interest were prioritized based on heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. A preliminary biochemical analysis of the activity of mitochondrial respiratory complexes was also performed on fresh-frozen GBM samples. Although a high number of mutations was detected, we report that the large majority of them does not pass the prioritization filters. Therefore, a relatively limited burden of pathogenic mutations is indeed carried by GBM, which did not appear to determine a general impairment of the respiratory chain. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Response to US review rules on patent subject matter of traditional Chinese medicine compositions].

PubMed

Liu, Pan; Cao, Ya-di; Gong, Rui-Juan; Liu, Wei

2018-02-01

The United States Patent and Trademark Office(USPTO) issued Interim Guidance on Patent Subject Matter Eligibility on December 16， 2014， bringing certain effects to the review rules on patent application of Chinese medicine compositions. Based on the Interim Guidance， cases analysis was used in this paper to analyze the patent subject matter issues of traditional Chinese medicine compositions in the United States. The researches have shown that the application documents should be properly written in the United States when the patent for Chinese medicine compositions is applied， which can improve the probability of authorization. Copyright© by the Chinese Pharmaceutical Association.

Mobile source air toxics mitigation measures.

DOT National Transportation Integrated Search

2013-10-01

In accordance with the Federal Highway Administration (FHWA) Interim Guidance Update on Mobile Source Air Toxic Analysis in NEPA Documents (September 30, 2009), transportation projects subject to the National Environmental Policy Act (NEPA) mus...

Safe Passage Data Analysis: Interim Report

DOT National Transportation Integrated Search

1993-04-01

The purpose of this report is to describe quantitatively the costs and benefits of screener : proficiency evaluation and reporting systems (SPEARS) equipment, particularly computer-based : instruction (CBI) systems, compared to current methods of tra...

Genomic understanding of glioblastoma expanded

Cancer.gov

Glioblastoma multiforme (GBM) was the first cancer type to be systematically studied by TCGA in 2008. In a new, complementary report, TCGA experts examined more than 590 GBM samples--the largest to date utilizing genomic characterization techniques and ne

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2

ClinicalTrials.gov

2018-04-09

Malignant Glioma of Brain; Astrocytoma; Malignant Astrocytoma; Oligodendroglioma; Anaplastic Oligodendroglioma of Brain (Diagnosis); Mixed Oligo-Astrocytoma; Ependymoma; Ganglioglioma; Pylocytic/Pylomyxoid Astrocytoma; Brain Tumor; Glioma; Brain Cancer; Glioblastoma; Glioblastoma Multiforme

Analysis of the factors that impact the reliability of high level waste canister materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyd, W.K.; Hall, A.M.

1977-09-19

The analysis encompassed identification and analysis of potential threats to canister integrity arising in the course of waste solidification, interim storage at the fuels reprocessing plant, wet and dry shipment, and geologic storage. Fabrication techniques and quality assurance requirements necessary to insure optimum canister reliability were considered taking into account such factors as welding procedure, surface preparation, stress relief, remote weld closure, and inspection methods. Alternative canister materials and canister systems were also considered in terms of optimum reliability in the face of threats to the canister's integrity, ease of fabrication, inspection, handling and cost. If interim storage in airmore » is admissible, the sequence suggested comprises producing a glass-type waste product in a continuous ceramic melter, pouring into a carbon steel or low-alloy steel canister of moderately heavy wall thickness, storing in air upright on a pad and surrounded by a concrete radiation shield, and thereafter placing in geologic storage without overpacking. Should the decision be to store in water during the interim period, then use of either a 304 L stainless steel canister overpacked with a solution-annealed and fast-cooled 304 L container, or a single high-alloy canister, is suggested. The high alloy may be Inconel 600, Incoloy Alloy 800, or Incoloy Alloy 825. In either case, it is suggested that the container be overpacked with a moderately heavy wall carbon steel or low-alloy steel cask for geologic storage to ensure ready retrievability. 19 figs., 5 tables.« less

Safety and efficacy of long-term treatment with teneligliptin: Interim analysis of a post-marketing surveillance of more than 10,000 Japanese patients with type 2 diabetes mellitus.

PubMed

Kadowaki, Takashi; Haneda, Masakazu; Ito, Hiroshi; Ueno, Makoto; Matsukawa, Miyuki; Yamakura, Tomoko; Sasaki, Kazuyo; Kimura, Mayumi; Iijima, Hiroaki

2018-02-01

This post-marketing surveillance examined the safety and efficacy of long-term teneligliptin therapy in Japanese patients. We report interim results (cut-off date: 28 June 2017) of a 3-year PMS undertaken in subjects with type 2 diabetes mellitus (T2DM). Survey items included demographics, treatments, adverse drug reactions (ADRs), and laboratory variables. A subgroup analysis was also performed across three age groups (<65 years; 65 to <75 years; ≥75 years). Main outcome measures were incidence of ADRs, laboratory variables, and change in glycated hemoglobin (HbA1c) from baseline over time. Of 11,677 patients registered, data from 10,532 patients (6,338 males/4,194 females) were analyzed for the safety analysis set; the median administration period was 731 days. Overall, ADRs and serious ADRs were reported in 364 (3.46%) and 91 patients (0.86%), respectively. The most common ADRs were all hypoglycemia (0.32%), constipation (0.27%), and hepatic function abnormal (0.24%). No change in mean body weight occurred, and a reduction in mean HbA1c was observed until 2 years. The safety and efficacy profiles did not differ markedly among the three age groups. These interim results show that teneligliptin was well tolerated and improved hyperglycemia in Japanese patients with T2DM in clinical practice.

Overview of current immunotherapeutic strategies for glioma

PubMed Central

Calinescu, Anda-Alexandra; Kamran, Neha; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro Ricardo; Castro, Maria Graciela

2015-01-01

In the last decade, numerous studies of immunotherapy for malignant glioma (glioblastoma multiforme) have brought new knowledge and new hope for improving the prognosis of this incurable disease. Some clinical trials have reached Phase III, following positive outcomes in Phase I and II, with respect to safety and immunological end points. Results are encouraging especially when considering the promise of sustained efficacy by inducing antitumor immunological memory. Progress in understanding the mechanisms of tumor-induced immune suppression led to the development of drugs targeting immunosuppressive checkpoints, which are used in active clinical trials for glioblastoma multiforme. Insights related to the heterogeneity of the disease bring new challenges for the management of glioma and underscore a likely cause of therapeutic failure. An emerging therapeutic strategy is represented by a combinatorial, personalized approach, including the standard of care: surgery, radiation, chemotherapy with added active immunotherapy and multiagent targeting of immunosuppressive checkpoints. PMID:26598957

Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

PubMed Central

Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

2016-01-01

Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology. PMID:27148537

Glioblastoma Multiforme and Lipid Nanocapsules: A Review.

PubMed

Aparicio-Blanco, Juan; Torres-Suárez, Ana-Isabel

2015-08-01

Epidemiological data on central nervous system disorders call for a focus on the major hindrance to brain drug delivery, blood-central nervous system barriers. Otherwise, there is little chance of improving the short-term survival of patients with diseases such as glioblastoma multiforme, which is one of the brain disorders associated with many years of life lost. Targetable nanocarriers for treating malignant gliomas are a unique way to overcome low chemotherapeutic levels at target sites devoid of systemic toxicity. This review describes the currently available targetable nanocarriers, focusing particularly on one of the newest nanocarriers, lipid nanocapsules. All of the strategies that are likely to be exploited by lipid nanocapsules to bypass blood-central nervous system barriers, including the most recent targeting approaches (mesenchymal cells), and novel administration routes (convection enhanced delivery) are discussed, together with their most remarkable achievements in glioma-implanted animal models. Although these systems are promising, much research remains to be done in this field.

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

NASA Astrophysics Data System (ADS)

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.

Role of 5-ALA in improving extent of tumour resection in patients with Glioblastoma Multiforme.

PubMed

Waqas, Muhammad; Khan, Inamullah; Shamim, Muhammad Shahzad

2017-10-01

Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use of 5- ALA in improving the extent of resection when compared to white light microscopy. A systematic review on the topic had a similar conclusion. Few studies have also hinted on a high false negative rate with the use of this technique..

Significant anti-tumor effect of bevacizumab in treatment of pineal gland glioblastoma multiforme.

PubMed

Mansour, Joshua; Fields, Braxton; Macomson, Samuel; Rixe, Olivier

2014-12-01

Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas. Current standard treatment for GBM involves a combination of cytoreduction through surgical resection, followed by radiation with concomitant and adjuvant chemotherapy (temozolomide). The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly. Furthermore, tumors present in the pineal gland are extremely rare, accounting for only 0.1-0.4 % of all adult brain tumors, with this location adding to the complexity of treatment. We present a case of GBM, at the rare location of pineal gland, in an elderly patient who was refractory to initial standard of care treatment with radiation and concomitant and adjuvant temozolomide, but who developed a significant response to anti-angiogenic therapy using bevacizumab.

[Palliative care in Primary Care: presentation of a case].

PubMed

Álvarez-Cordovés, M M; Mirpuri-Mirpuri, P G; Gonzalez-Losada, J; Chávez-Díaz, B

2013-10-01

We present a case of a patient diagnosed with glioblastoma multiforme refractory to treatment. Glioblastoma multiforme is the most common primary brain tumour and unfortunately the most aggressive, with an estimated mortality of about 90% in the first year after diagnosis. In our case the patient had reached a stage of life where quality of life was importsnt, with palliative care being the only recourse. The family is the mainstay in the provision of care of terminally ill patients, and without their active participation it would be difficult to achieve the objectives in patient care. We must also consider the family of the terminally ill in our care aim, as its members will experience a series of changes that will affect multiple areas where we should take action. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Moisture balance over the Iberian Peninsula computed using a high resolution regional climate model. The impact of 3DVAR data assimilation.

NASA Astrophysics Data System (ADS)

González-Rojí, Santos J.; Sáenz, Jon; Ibarra-Berastegi, Gabriel

2016-04-01

A numerical downscaling exercise over the Iberian Peninsula has been run nesting the WRF model inside ERA Interim. The Iberian Peninsula has been covered by a 15km x 15 km grid with 51 vertical levels. Two model configurations have been tested in two experiments spanning the period 2010-2014 after a one year spin-up (2009). In both cases, the model uses high resolution daily-varying SST fields and the Noah land surface model. In the first experiment (N), after the model is initialised, boundary conditions drive the model, as usual in numerical downscaling experiments. The second experiment (D) is configured the same way as the N case, but 3DVAR data assimilation is run every six hours (00Z, 06Z, 12Z and 18Z) using observations obtained from the PREPBUFR dataset (NCEP ADP Global Upper Air and Surface Weather Observations) using a 120' window around analysis times. For the data assimilation experiment (D), seasonally (monthly) varying background error covariance matrices have been prepared according to the parameterisations used and the mesoscale model domain. For both N and D runs, the moisture balance of the model runs has been evaluated over the Iberian Peninsula, both internally according to the model results (moisture balance in the model) and also in terms of the observed moisture fields from observational datasets (particularly precipitable water and precipitation from observations). Verification has been performed both at the daily and monthly time scales. The verification has also been performed for ERA Interim, the driving coarse-scale dataset used to drive the regional model too. Results show that the leading terms that must be considered over the area are the tendency in the precipitable water column, the divergence of moisture flux, evaporation (computed from latent heat flux at the surface) and precipitation. In the case of ERA Interim, the divergence of Qc is also relevant, although still a minor player in the moisture balance. Both mesoscale model runs are more effective at closing the moisture balance over the whole Iberian Peninsula than ERA Interim. The N experiment (no data assimilation) shows a better closure than the D case, as could be expected from the lack of analysis increments in it. This result is robust both at the daily and monthly time scales. Both ERA Interim and the D experiment produce a negative residual in the balance equation (compatible with excess evaporation or increased convergence of moisture over the Iberian Peninsula). This is a result of the data assimilation process in the D dataset, since in the N experiment the residual is mainly positive. The seasonal cycle of evaporation is much closer in the D experiment to the one in ERA Interim than in the N case, with a higher evaporation during summer months. However, both regional climate model runs show a lower evaporation rate than ERA Interim, particularly during summer months.

An interim reference model for the variability of the middle atmosphere H2O vapor distribution

NASA Technical Reports Server (NTRS)

Remsberg, E. E.; Russell, J. M., III; Wu, C. Y.

1989-01-01

Water vapor is an important minor constituent in the studies of the middle atmosphere for a variety of reasons, including its role as a source for active HO(y) chemicals and its use in analysis of transport processes. A number of in situ and remote techniques were employed in the determination of water vapor distributions. Two of the more complete data sets were used to develop an interim reference profile. First, there are the seven months of Nimbus 7 limb infrared monitor of the stratosphere (LIMS) data obtained during Nov. 1978 to May 1979 over the range 64S to 84N latitude and from about 100 to 1 mb in the mid-mesosphere at several fixed Northern Hemisphere mid-latitude sites. These two data sets were combined to give a mid-lattitude, interim reference water vapor profile for the entire vertical range of the middle atmosphere and with accuracies of better than 25 percent. The daily variability of stratospheric water vapor profiles about the monthly mean was also established from these data sets for selected months. Information is also provided on the longitudinal variability of LIMS water vapor profiles about the daily, weekly, and monthly zonal means. Generally, the interim reference water vapor profile and its variability are consistent with prevailing ideas about chemistry and transport.

Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy.

PubMed

Grunnet, M L; O'Neill, A; Gilbert, M; Hellman, R

2000-01-01

The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme. Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation. There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices. Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

PubMed

Schrot, Rudolph J; Ma, Joyce H; Greco, Claudia M; Arias, Angelo D; Angelastro, James M

2007-11-01

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

Replacement of a hopeless maxillary central incisor: a technique for the fabrication of an immediate implant-supported interim restoration.

PubMed

Graiff, Lorenzo; Vigolo, Paolo

2012-04-01

Placement of a dental implant and an interim restoration in the esthetic zone immediately following tooth extraction is now a common procedure. However, in such clinical situations, the fabrication of an appropriate interim restoration may be challenging. The aim of this article is to present a technique for modifying the extracted tooth so it can be used as an implant-supported interim restoration.

Interim analysis of STR effectiveness

DOT National Transportation Integrated Search

1978-01-01

The present report describes the status of the NHTSA Short Term Rehabilitation Study (STR) as of December, 1977, and summarizes the progress of data collection efforts by the eleven participating ASAP projects. Outcome measures considered as indicati...

Palbociclib for Advanced Breast Cancer

Cancer.gov

An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.

PubMed

Aggarwal, Swati P; Zinman, Lorne; Simpson, Elizabeth; McKinley, Jane; Jackson, Katherine E; Pinto, Hanika; Kaufman, Petra; Conwit, Robin A; Schoenfeld, David; Shefner, Jeremy; Cudkowicz, Merit

2010-05-01

In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS. We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0.68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389. At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0.51). The hazard ratio of reaching the primary endpoint was 1.13 (95% CI 0.61-2.07). The study was stopped at the first interim analysis because criterion for futility was met (p=0.78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0.15 (95% CI -0.43 to 0.73, p=0.61). There were no major safety concerns. Falls (p=0.04) and back pain (p=0.05) were more common in the lithium group than in the placebo group. We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS. National Institute of Neurological Disorders and Stroke, ALS Association, and ALS Society of Canada. Copyright 2010 Elsevier Ltd. All rights reserved.

The role of the Data and Safety Monitoring Board in a clinical trial: the CRISIS study.

PubMed

Holubkov, Richard; Casper, T Charles; Dean, J Michael; Anand, K J S; Zimmerman, Jerry; Meert, Kathleen L; Newth, Christopher J L; Berger, John; Harrison, Rick; Willson, Douglas F; Nicholson, Carol

2013-05-01

Randomized clinical trials are commonly overseen by a Data and Safety Monitoring Board comprised of experts in medicine, ethics, and biostatistics. Data and Safety Monitoring Board responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. Data and Safety Monitoring Board decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate Data and Safety Monitoring Board oversight into the design, monitoring, and reporting of randomized trials. Case study, narrative review. The Data and Safety Monitoring Board's role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. The National Institutes of Health-appointed CRISIS Data and Safety Monitoring Board was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested Data and Safety Monitoring Board interim review before opening CRISIS to children below 1 yr of age. The first interim analysis found higher 28-day mortality in one treatment arm. The Data and Safety Monitoring Board maintained trial closure to younger children and requested a second interim data review 6 months later. At this second meeting, mortality was no longer of concern, whereas a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the Data and Safety Monitoring Board elected to examine conditional power and unmask treatment arm identities. On finding somewhat greater efficacy in the placebo arm, the Data and Safety Monitoring Board recommended stopping CRISIS due to futility. The design and operating procedures of a multicenter randomized trial must consider a pivotal Data and Safety Monitoring Board role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The Data and Safety Monitoring Board must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups.

Comparison of trends and abrupt changes of the South Asia high from 1979 to 2014 in reanalysis and radiosonde datasets

NASA Astrophysics Data System (ADS)

Shi, Chunhua; Huang, Ying; Guo, Dong; Zhou, Shunwu; Hu, Kaixi; Liu, Yu

2018-05-01

The South Asian High (SAH) has an important influence on atmospheric circulation and the Asian climate in summer. However, current comparative analyses of the SAH are mostly between reanalysis datasets and there is a lack of sounding data. We therefore compared the climatology, trends and abrupt changes in the SAH in the Japanese 55-year Reanalysis (JRA-55) dataset, the National Centers for Environmental Prediction Climate Forecast System Reanalysis (NCEP-CFSR) dataset, the European Center for Medium-Range Weather Forecasts Reanalysis Interim (ERA-interim) dataset and radiosonde data from China using linear analysis and a sliding t-test. The trends in geopotential height in the control area of the SAH were positive in the JRA-55, NCEP-CFSR and ERA-interim datasets, but negative in the radiosonde data in the time period 1979-2014. The negative trends for the SAH were significant at the 90% confidence level in the radiosonde data from May to September. The positive trends in the NCEP-CFSR dataset were significant at the 90% confidence level in May, July, August and September, but the positive trends in the JRA-55 and ERA-Interim were only significant at the 90% confidence level in September. The reasons for the differences in the trends of the SAH between the radiosonde data and the three reanalysis datasets in the time period 1979-2014 were updates to the sounding systems, changes in instrumentation and improvements in the radiation correction method for calculations around the year 2000. We therefore analyzed the trends in the two time periods of 1979-2000 and 2001-2014 separately. From 1979 to 2000, the negative SAH trends in the radiosonde data mainly agreed with the negative trends in the NCEP-CFSR dataset, but were in contrast with the positive trends in the JRA-55 and ERA-Interim datasets. In 2001-2014, however, the trends in the SAH were positive in all four datasets and most of the trends in the radiosonde and NCEP-CFSR datasets were significant. It is therefore better to use the NCEP-CFSR dataset than the JRA-55 and ERA-Interim datasets when discussing trends in the SAH.

TECNOB Study: Ad Interim Results of a Randomized Controlled Trial of a Multidisciplinary Telecare Intervention for Obese Patients with Type-2 Diabetes.

PubMed

Castelnuovo, Gianluca; Manzoni, Gian Mauro; Cuzziol, Paola; Cesa, Gian Luca; Corti, Stefania; Tuzzi, Cristina; Villa, Valentina; Liuzzi, Antonio; Petroni, Maria Letizia; Molinari, Enrico

2011-03-04

Obesity increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private care-costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. Information and communication technologies (ICT) can help clinicians to deliver treatment in a cost-effective and time-saving manner to a large number of obese individuals with co-morbidities. To examine ad interim effectiveness of a 12-month multidisciplinary telecare intervention for weight loss provided to obese patients with type 2 diabetes. A single-center randomized controlled trial (TECNOB study) started in December 2008. At present, 72 obese patients with type 2 diabetes have been recruited and randomly allocated to the TECNOB program (n=37) or to a control condition (n=39). However, only 34 participants have completed at least the 3-month follow-up and have been included in this ad interim analysis. 21 out of them have reached also the 6-month follow-up and 13 have achieved the end of the program. Study is still on-going. All participants attended 1-month inpatient intensive program that involved individualized medical care, diet therapy, physical training and brief psychological counseling. At discharge, participants allocated to the TECNOB program were instructed to use a weight-loss web-site, a web-based videoconference tool, a dietary software installed into their cellular phones and an electronic armband measuring daily steps and energy expenditure. Weight and disordered eating-related behaviors and cognitions (EDI-2) at entry to hospital, at discharge from hospital, at 3,6 and 12 months. Ad interim analysis of data from 34 participants showed no statistically significant difference between groups in weight change at any time-point. However, within-group analysis revealed significant reductions of initial weight at discharge from hospital, at 3 months, at 6 months but not at 12 months. Control group had higher scores in Interpersonal distrust at 12 months. This ad interim findings revealed that the effect of the inpatient treatment was high and probably overwhelmed the effect of the TECNOB intervention. Much statistical power and long-term follow-up may enhance the probability to detect the TECNOB effect over and above the great one exerted by the inpatient program.

International validation study for interim PET in ABVD-treated, advanced-stage hodgkin lymphoma: interpretation criteria and concordance rate among reviewers.

PubMed

Biggi, Alberto; Gallamini, Andrea; Chauvie, Stephane; Hutchings, Martin; Kostakoglu, Lale; Gregianin, Michele; Meignan, Michel; Malkowski, Bogdan; Hofman, Michael S; Barrington, Sally F

2013-05-01

At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α. The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.

Guidance: Interim Municipal Settlement Policy

EPA Pesticide Factsheets

Interim guidance and fact sheets regarding settlements involving municipalities or municipal waste under Section 122 CERCLA as amended by SARA. Interim policy sets forth the criteria by which EPA generally determines whether to exercise enforcement discretion to pursue MSW generators and transporters as PRPs.

Photomorphic analysis techniques: An interim spatial analysis using satellite remote sensor imagery and historical data

NASA Technical Reports Server (NTRS)

Keuper, H. R.; Peplies, R. W.; Gillooly, R. P.

1977-01-01

The use of machine scanning and/or computer-based techniques to provide greater objectivity in the photomorphic approach was investigated. Photomorphic analysis and its application in regional planning are discussed. Topics included: delineation of photomorphic regions; inadequacies of existing classification systems; tonal and textural characteristics and signature analysis techniques; pattern recognition and Fourier transform analysis; and optical experiments. A bibliography is included.

Science Opportunities Enabled by NASA's Constellation System: Interim Report

NASA Astrophysics Data System (ADS)

Committee On Science Opportunities Enabled By Nasa'S Constellation System, National Research Council

To begin implementation of the Vision for Space Exploration (recently renamed "United States Space Exploration Policy"), NASA has begun development of new launch vehicles and a human-carrying spacecraft that are collectively called the Constellation System. In November 2007, NASA asked the NRC to evaluate the potential for the Constellation System to enable new space science opportunities. For this interim report, 11 existing "Vision Mission" studies of advanced space science mission concepts inspired by earlier NASA forward-looking studies were evaluated. The focus was to assess the concepts and group them into two categories: more-deserving or less deserving of future study. This report presents a description of the Constellation System and its opportunities for enabling new space science opportunities, and a systematic analysis of the 11 Vision Mission studies. For the final report, the NRC issued a request for information to the relevant communities to obtain ideas for other mission concepts that will be assessed by the study committee, and several issues addressed only briefly in the interim report will be explored more fully.

NAVSTAR GPS Simulation and Analysis Program (Interim Report)

DOT National Transportation Integrated Search

1983-10-01

This study assesses the capability of the planned NAVSTAR Global Positioning System (GPS) to meet civil navigation requirements. When it becomes operational in about 1983, NAVSTAR GPS will provide accurate two-dimensional and three-dimensional servic...

75 FR 65349 - Decision To Evaluate a Petition To Designate a Class of Employees From BWX Technologies Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

...: Lynchburg, Virginia. Job Titles and/or Job Duties: All Atomic Weapons Employer employees. Period of..., Interim Director, Division of Compensation Analysis and Support, National Institute for Occupational...

75 FR 4822 - Decision To Evaluate a Petition To Designate a Class of Employees for the Lawrence Livermore...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...: Lawrence Livermore National Laboratory. Location: Livermore, California. Job Titles and/or Job Duties: All... L. Hinnefeld, Interim Director, Office of Compensation Analysis and Support, National Institute for...

Road weather connected vehicle applications : benefit-cost analysis interim report.

DOT National Transportation Integrated Search

2013-01-01

RWMP is currently engaged in a project to evaluate the potential benefits of road weather connected vehicle applications. Of particular interest are the potential improvements in safety, reductions in travel time, improved travel reliability, reducti...

INTERIM ANALYSIS OF THE CONTRIBUTION OF HIGH-LEVEL EVIDENCE FOR DENGUE VECTOR CONTROL.

PubMed

Horstick, Olaf; Ranzinger, Silvia Runge

2015-01-01

This interim analysis reviews the available systematic literature for dengue vector control on three levels: 1) single and combined vector control methods, with existing work on peridomestic space spraying and on Bacillus thuringiensis israelensis; further work is available soon on the use of Temephos, Copepods and larvivorous fish; 2) or for a specific purpose, like outbreak control, and 3) on a strategic level, as for example decentralization vs centralization, with a systematic review on vector control organization. Clear best practice guidelines for methodology of entomological studies are needed. There is a need to include measuring dengue transmission data. The following recommendations emerge: Although vector control can be effective, implementation remains an issue; Single interventions are probably not useful; Combinations of interventions have mixed results; Careful implementation of vector control measures may be most important; Outbreak interventions are often applied with questionable effectiveness.

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

76 FR 4369 - Special Law Enforcement Commissions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Special Law Enforcement Commissions AGENCY... of the Interim Special Law Enforcement Commission Policy, Rules and Procedures, the Interim Special Law Enforcement Commission Protocols and the Interim Domestic Violence Waiver that will be used by the...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Interim transport and termination pricing. 51... SERVICES (CONTINUED) INTERCONNECTION Reciprocal Compensation for Transport and Termination of Telecommunications Traffic § 51.715 Interim transport and termination pricing. (a) Upon request from a...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Interim transport and termination pricing. 51... SERVICES (CONTINUED) INTERCONNECTION Reciprocal Compensation for Transport and Termination of Telecommunications Traffic § 51.715 Interim transport and termination pricing. (a) Upon request from a...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

Investigation of Kelvin wave periods during Hai-Tang typhoon using Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Kishore, P.; Jayalakshmi, J.; Lin, Pay-Liam; Velicogna, Isabella; Sutterley, Tyler C.; Ciracì, Enrico; Mohajerani, Yara; Kumar, S. Balaji

2017-11-01

Equatorial Kelvin waves (KWs) are fundamental components of the tropical climate system. In this study, we investigate Kelvin waves (KWs) during the Hai-Tang typhoon of 2005 using Empirical Mode Decomposition (EMD) of regional precipitation, zonal and meridional winds. For the analysis, we use daily precipitation datasets from the Global Precipitation Climatology Project (GPCP) and wind datasets from the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-analysis (ERA-Interim). As an additional measurement, we use in-situ precipitation datasets from rain-gauges over the Taiwan region. The maximum accumulated precipitation was approximately 2400 mm during the period July 17-21, 2005 over the southwestern region of Taiwan. The spectral analysis using the wind speed at 950 hPa found in the 2nd, 3rd, and 4th intrinsic mode functions (IMFs) reveals prevailing Kelvin wave periods of ∼3 days, ∼4-6 days, and ∼6-10 days, respectively. From our analysis of precipitation datasets, we found the Kelvin waves oscillated with periods between ∼8 and 20 days.

78 FR 55339 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

...The Federal Deposit Insurance Corporation (FDIC) is adopting an interim final rule that revises its risk-based and leverage capital requirements for FDIC-supervised institutions. This interim final rule is substantially identical to a joint final rule issued by the Office of the Comptroller of the Currency (OCC) and the Board of Governors of the Federal Reserve System (Federal Reserve) (together, with the FDIC, the agencies). The interim final rule consolidates three separate notices of proposed rulemaking that the agencies jointly published in the Federal Register on August 30, 2012, with selected changes. The interim final rule implements a revised definition of regulatory capital, a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for FDIC-supervised institutions subject to the advanced approaches risk-based capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator. The interim final rule incorporates these new requirements into the FDIC's prompt corrective action (PCA) framework. In addition, the interim final rule establishes limits on FDIC-supervised institutions' capital distributions and certain discretionary bonus payments if the FDIC-supervised institution does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk-based capital requirements. The interim final rule amends the methodologies for determining risk-weighted assets for all FDIC-supervised institutions. The interim final rule also adopts changes to the FDIC's regulatory capital requirements that meet the requirements of section 171 and section 939A of the Dodd-Frank Wall Street Reform and Consumer Protection Act. The interim final rule also codifies the FDIC's regulatory capital rules, which have previously resided in various appendices to their respective regulations, into a harmonized integrated regulatory framework. In addition, the FDIC is amending the market risk capital rule (market risk rule) to apply to state savings associations. The FDIC is issuing these revisions to its capital regulations as an interim final rule. The FDIC invites comments on the interaction of this rule with other proposed leverage ratio requirements applicable to large, systemically important banking organizations. This interim final rule otherwise contains regulatory text that is identical to the common rule text adopted as a final rule by the Federal Reserve and the OCC. This interim final rule enables the FDIC to proceed on a unified, expedited basis with the other federal banking agencies pending consideration of other issues. Specifically, the FDIC intends to evaluate this interim final rule in the context of the proposed well- capitalized and buffer levels of the supplementary leverage ratio applicable to large, systemically important banking organizations, as described in a separate Notice of Proposed Rulemaking (NPR) published in the Federal Register August 20, 2013. The FDIC is seeking commenters' views on the interaction of this interim final rule with the proposed rule regarding the supplementary leverage ratio for large, systemically important banking organizations.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

42 CFR 417.574 - Interim settlement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Interim settlement. 417.574 Section 417.574 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... PLANS Medicare Payment: Cost Basis § 417.574 Interim settlement. (a) Determination. Within 30 days...

14 CFR 136.41 - Interim operating authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Interim operating authority. 136.41 Section 136.41 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... technology, as appropriate, and (9) Shall allow for modifications of the interim operating authority based on...

14 CFR 136.41 - Interim operating authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Interim operating authority. 136.41 Section 136.41 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... technology, as appropriate, and (9) Shall allow for modifications of the interim operating authority based on...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

10 CFR 590.403 - Emergency interim orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Opinions and Orders § 590.403 Emergency interim... and issue an emergency interim order authorizing the import or export of natural gas. After issuance...

EPA Interim Evaluation of 2016-2017 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2016-2017 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2016-2017 milestones, recognizing the achievements made in 2016.

EPA Interim Evaluation of 2012-2013 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2012-2013 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2012-2013 milestones, recognizing the achievements made in 2012.

49 CFR 37.193 - Interim service requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Interim service requirements. 37.193 Section 37.193 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.193 Interim service requirements. (a) Until...

76 FR 57657 - Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

...] Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This regulation establishes an extension of time-limited interim..., and Cosmetic Act (FFDCA). The time-limited tolerances expire on March 18, 2013. DATES: This regulation...

EPA Interim Evaluation of 2014-2015 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2014-2015 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2014-2015 milestones, recognizing the achievements made in 2014.

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

Contribution of postpolymerization conditioning and storage environments to the mechanical properties of three interim restorative materials.

PubMed

Thompson, Geoffrey A; Luo, Qing

2014-09-01

Because polymer-based interim restorative materials are weak, even well-made restorations sometimes fail before the definitive restoration is ready for insertion. Therefore, knowing which fabrication procedures and service conditions affect mechanical properties is important, particularly over an extended period. The purpose of this study was to evaluate the effect of thermal treatment, surface sealing, thermocycling, storage media, storage temperature, and age on autopolymerizing poly(methylmethacrylate) and bis-acryl interim restorative materials. Outcome measures were flexural strength, Vickers surface microhardness, and impact strength. Flexural strength and microhardness of poly(methylmethacrylate) (Jet Acrylic) and 2 bis-acryl-composite resin (Protemp 3 Garant and Integrity) interim restorative materials were evaluated as affected by storage media, storage temperature, storage time, thermocycling, postpolymerization thermal treatment, or application of a surface sealer. In total, 2880 beam specimens (25×2×2 mm) were fabricated. Mechanical property analyses were made at 10 days, 30 days, 6 months, and 1 year after specimen preparation. Flexural strength was determined by using a 3-point bending test in a universal testing machine with a 1 kN load cell at a crosshead speed of 5.0 mm min(-1). Fracture specimens were recovered and used for determining Vickers microhardness. Measurements were made with a 0.1 N load and 15 second dwell time. Three microhardness measurements were made for each specimen, and the mean was used for reporting Vickers microhardness. Notched impact specimens (64×12.7×6.35 mm) were fabricated from Jet, Protemp 3 Garant, and Integrity interim restorative materials, yielding 288 impact specimens. Impact strengths were assessed at 10 days, 30 days, 6 months, and 1 year with a 2 J pendulum. The effects of the various experimental treatments were determined and rank ordered with analysis of variance, F ratios, and least square means differences Student t tests (α=.05). All experimental treatments investigated had significant effects on flexural strength, with material (P<.001) and thermocycling (P<.001) being dominant. Moreover, all experimental treatments investigated had a significant overall impact on Vickers microhardness with material (P<.001) and Palaseal glaze (P<.001) showing large effects. Material (P<.001) and age (P=.010) had a significant effect on impact strength. Mechanical properties of some interim polymeric materials can be improved by postpolymerization heat treatments or surface glazing. This procedure may extend the useful lifetime of some bis-acryl interim restorations. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

An interim prosthesis program for lower limb amputees: comparison of public and private models of service.

PubMed

Gordon, Robert; Magee, Christopher; Frazer, Anna; Evans, Craig; McCosker, Kathryn

2010-06-01

This study compared the outcomes of an interim mechanical prosthesis program for lower limb amputees operated under a public and private model of service. Over a two-year period, 60 transtibial amputees were fitted with an interim prosthesis as part of their early amputee care. Thirty-four patients received early amputee care under a public model of service, whereby a prosthetist was employed to provide the interim mechanical prosthesis service. The remaining 26 patients received early amputee care under a private model of service, where an external company was contracted to provide the interim mechanical prosthesis service. The results suggested comparable clinical outcomes between the two patient groups. However, the public model appeared to be less expensive with the average labour cost per patient being 29.0% lower compared with the private model. The results suggest that a public model of service may provide a more comprehensive and less expensive interim prosthesis program for lower limb amputees.

Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis.

PubMed

Miller, Frank; Björnsson, Marcus; Svensson, Ola; Karlsten, Rolf

2014-03-01

Dose-finding studies in non-oncology areas are usually conducted in Phase II of the development process of a new potential medicine and it is key to choose a good design for such a study, as the results will decide if and how to proceed to Phase III. The present article has focus on the design of a dose-finding study for pain in osteoarthritis patients treated with the TRPV1 antagonist AZD1386. We describe different design alternatives in the planning of this study, the reasoning for choosing the adaptive design and experiences with conduct and interim analysis. Three alternatives were proposed: one single dose-finding study with parallel design, a programme with a smaller Phase IIa study followed by a Phase IIb dose-finding study, and an adaptive dose-finding study. We describe these alternatives in detail and explain why the adaptive design was chosen for the study. We give insights in design aspects of the adaptive study, which need to be pre-planned, like interim decision criteria, statistical analysis method and setup of a Data Monitoring Committee. Based on the interim analysis it was recommended to stop the study for futility since AZD1386 showed no significant pain decrease based on the primary variable. We discuss results and experiences from the conduct of the study with the novel design approach. Huge cost savings have been done compared to if the option with one dose-finding design for Phase II had been chosen. However, we point out several challenges with this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Regional Climate Model sesitivity to different parameterizations schemes with WRF over Spain

NASA Astrophysics Data System (ADS)

García-Valdecasas Ojeda, Matilde; Raquel Gámiz-Fortis, Sonia; Hidalgo-Muñoz, Jose Manuel; Argüeso, Daniel; Castro-Díez, Yolanda; Jesús Esteban-Parra, María

2015-04-01

The ability of the Weather Research and Forecasting (WRF) model to simulate the regional climate depends on the selection of an adequate combination of parameterization schemes. This study assesses WRF sensitivity to different parameterizations using six different runs that combined three cumulus, two microphysics and three surface/planetary boundary layer schemes in a topographically complex region such as Spain, for the period 1995-1996. Each of the simulations spanned a period of two years, and were carried out at a spatial resolution of 0.088° over a domain encompassing the Iberian Peninsula and nested in the coarser EURO-CORDEX domain (0.44° resolution). The experiments were driven by Interim ECMWF Re-Analysis (ERA-Interim) data. In addition, two different spectral nudging configurations were also analysed. The simulated precipitation and maximum and minimum temperatures from WRF were compared with Spain02 version 4 observational gridded datasets. The comparison was performed at different time scales with the purpose of evaluating the model capability to capture mean values and high-order statistics. ERA-Interim data was also compared with observations to determine the improvement obtained using dynamical downscaling with respect to the driving data. For this purpose, several parameters were analysed by directly comparing grid-points. On the other hand, the observational gridded data were grouped using a multistep regionalization to facilitate the comparison in term of monthly annual cycle and the percentiles of daily values analysed. The results confirm that no configuration performs best, but some combinations that produce better results could be chosen. Concerning temperatures, WRF provides an improvement over ERA-Interim. Overall, model outputs reduce the biases and the RMSE for monthly-mean maximum and minimum temperatures and are higher correlated with observations than ERA-Interim. The analysis shows that the Yonsei University planetary boundary layer scheme is the most appropriate parameterization in term of temperatures because it better describes monthly minimum temperatures and seems to perform well for maximum temperatures. Regarding precipitation, ERA-Interim time series are slightly higher correlated with observations than WRF, but the bias and the RMSE are largely worse. These results also suggest that CAM V.5.1 2-moment 5-class microphysics schemes should not be used due to the computational cost with no apparent gain with respect to simpler schemes such as WRF single-moment 3-class. For the convection scheme, this study suggests that Betts-Miller-Janjic scheme is an appropriate choice due to its robustness and Kain-Fritsch cumulus scheme should not be used over this region. KEY WORDS: Regional climate modelling, physics schemes, parameterizations, WRF. ACKNOWLEDGEMENTS This work has been financed by the projects P11-RNM-7941 (Junta de Andalucía-Spain) and CGL2013-48539-R (MINECO-Spain, FEDER).

78 FR 14487 - Tetrachlorvinphos; Proposed Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

...] Tetrachlorvinphos; Proposed Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: This regulation proposes the extension of the time-limited... related to EPA's extension of the time-limited interim tolerances for the combined residues of the...

78 FR 15880 - Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This regulation extends the time-limited interim tolerances for the... . II. Background A detailed summary of the background related to EPA's extension of the time-limited...

24 CFR 115.207 - Consequences of interim certification and certification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consequences of interim certification and certification. 115.207 Section 115.207 Housing and Urban Development Regulations Relating to... ENFORCEMENT AGENCIES Certification of Substantially Equivalent Agencies § 115.207 Consequences of interim...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 8 2012-10-01 2012-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

76 FR 74834 - Interim Staff Guidance on Aging Management Program for Steam Generators

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... NRC staff's evaluation of the suitability of using Revision 3 of the Nuclear Energy Institute's (NEI... NUCLEAR REGULATORY COMMISSION [NRC-2011-0228] Interim Staff Guidance on Aging Management Program for Steam Generators AGENCY: Nuclear Regulatory Commission. ACTION: Interim staff guidance; issuance...

75 FR 58390 - Decision To Evaluate a Petition To Designate a Class of Employees From the Vitro Manufacturing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... Manufacturing. Location: Canonsburg, Pennsylvania. Job Titles and/or Job Duties: All employees who worked in any...: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute...

75 FR 24957 - Decision to Evaluate a Petition to Designate a Class of Employees From BWX Technologies Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

.... Job Titles and/or Job Duties: All Atomic Weapons Employer employees. Period of Employment: January 1... INFORMATION CONTACT: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support...

75 FR 22409 - Decision To Evaluate a Petition To Designate a Class of Employees From the Sandia National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

.... Location: Albuquerque, New Mexico. Job Titles and/or Job Duties: All employees who worked within the... CONTACT: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National...

Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.

PubMed

Bartha, Erzsebet; Davidson, Thomas; Brodtkorb, Thor-Henrik; Carlsson, Per; Kalman, Sigridur

2013-07-09

A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million. If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as 'further research is needed' are replaced with 'further research is cost-effective and 'further funding of a trial is justified'. ClinicalTrials.gov NCT01141894.

PTEN Loss Does Not Predict for Response to RAD001 (Everolimus) in a Glioblastoma Orthotopic Xenograft Test Panel

PubMed Central

Yang, Lin; Clarke, Michelle J.; Carlson, Brett L.; Mladek, Ann C.; Schroeder, Mark A.; Decker, Paul; Wu, Wenting; Kitange, Gaspar J.; Grogan, Patrick T.; Goble, Jennie M.; Uhm, Joon; Galanis, Evanthia; Giannini, Caterina; Lane, Heidi A.; James, C. David; Sarkaria, Jann N.

2014-01-01

Purpose Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). Experimental Design To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Results Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. Conclusion These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme. PMID:18559622

Initial care and outcome of glioblastoma multiforme patients in 2 diverse health care scenarios in Brazil: does public versus private health care matter?.

PubMed

Loureiro, Luiz Victor Maia; Pontes, Lucíola de Barros; Callegaro-Filho, Donato; Koch, Ludmila de Oliveira; Weltman, Eduardo; Victor, Elivane da Silva; Santos, Adrialdo José; Borges, Lia Raquel Rodrigues; Segreto, Roberto Araújo; Malheiros, Suzana Maria Fleury

2014-07-01

The aim of this study was to describe the epidemiological and survival features of patients with glioblastoma multiforme treated in 2 health care scenarios--public and private--in Brazil. We retrospectively analyzed clinical, treatment, and outcome characteristics of glioblastoma multiforme patients from 2003 to 2011 at 2 institutions. The median age of the 171 patients (117 public and 54 private) was 59.3 years (range, 18-84). The median survival for patients treated in private institutions was 17.4 months (95% confidence interval, 11.1-23.7) compared with 7.1 months (95% confidence interval, 3.8-10.4) for patients treated in public institutions (P < .001). The time from the first symptom to surgery was longer in the public setting (median of 64 days for the public hospital and 31 days for the private institution; P = .003). The patients at the private hospital received radiotherapy concurrent with chemotherapy in 59.3% of cases; at the public hospital, only 21.4% (P < .001). Despite these differences, the institution of treatment was not found to be an independent predictor of outcome (hazard ratio, 1.675; 95% confidence interval, 0.951-2.949; P = .074). The Karnofsky performance status and any additional treatment after surgery were predictors of survival. A hazard ratio of 0.010 (95% confidence interval, 0.003-0.033; P < .001) was observed for gross total tumor resection followed by radiotherapy concurrent with chemotherapy. Despite obvious disparities between the hospitals, the medical assistance scenario was not an independent predictor of survival. However, survival was directly influenced by additional treatment after surgery. Therefore, increasing access to resources in developing countries like Brazil is critical.

Meningiomas, dicentric chromosomes, gliomas, and telomerase activity.

PubMed

Carroll, T; Maltby, E; Brock, I; Royds, J; Timperley, W; Jellinek, D

1999-08-01

Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were telomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre-crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright 1999 John Wiley & Sons, Ltd.

Replication-Dependent Radiosensitization of Human Glioma Cells by Inhibition of Poly(ADP-Ribose) Polymerase: Mechanisms and Therapeutic Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dungey, Fiona A.; Loeser, Dana A.; Chalmers, Anthony J.

2008-11-15

Purpose: Current treatments for glioblastoma multiforme are inadequate and limited by the radiation sensitivity of normal brain. Because glioblastoma multiforme are rapidly proliferating tumors within nondividing normal tissue, the therapeutic ratio might be enhanced by combining radiotherapy with a replication-specific radiosensitizer. KU-0059436 (AZD2281) is a potent and nontoxic inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) undergoing a Phase II clinical trial as a single agent. Methods and Materials: Based on previous observations that the radiosensitizing effects of PARP inhibition are more pronounced in dividing cells, we investigated the mechanisms underlying radiosensitization of human glioma cells by KU-0059436, evaluating the replication dependence ofmore » this effect and its therapeutic potential. Results: KU-0059436 increased the radiosensitivity of four human glioma cell lines (T98G, U373-MG, UVW, and U87-MG). Radiosensitization was enhanced in populations synchronized in S phase and abrogated by concomitant exposure to aphidicolin. Sensitization was further enhanced when the inhibitor was combined with a fractionated radiation schedule. KU-0059436 delayed repair of radiation-induced DNA breaks and was associated with a replication-dependent increase in {gamma}H2AX and Rad51 foci. Conclusion: The results of our study have shown that KU-0059436 increases radiosensitivity in a replication-dependent manner that is enhanced by fractionation. A mechanism is proposed whereby PARP inhibition increases the incidence of collapsed replication forks after ionizing radiation, generating persistent DNA double-strand breaks. These observations indicate that KU-0059436 is likely to enhance the therapeutic ratio achieved by radiotherapy in the treatment of glioblastoma multiforme. A Phase I clinical trial is in development.« less

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

75 FR 13484 - Foreign-Trade Zone 22; Temporary/Interim Manufacturing Authority; LG Electronics Mobilecomm USA...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... DEPARTMENT OF COMMERCE [Docket T-1-2010] Foreign-Trade Zones Board Foreign-Trade Zone 22; Temporary/Interim Manufacturing Authority; LG Electronics Mobilecomm USA, Inc. (Cell Phones); Notice of.../ interim manufacturing (T/IM) authority, on behalf of LG Electronics Mobilecomm USA, Inc. (LGEMU), to...

76 FR 37781 - Foreign-Trade Zone 26; Atlanta, GA; Application for Temporary/Interim Manufacturing Authority...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

..., GA; Application for Temporary/ Interim Manufacturing Authority; Makita Corporation of America; (Hand- Held Power Tool and Gasoline/Electric-Powered Garden Product Manufacturing); Buford, GA An application... Georgia Foreign-Trade Zone, Inc., grantee of FTZ 26, requesting temporary/interim manufacturing (T/IM...

Interim Action Proposed Plan for the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, J.

2002-06-18

The purpose of this Interim Action Proposed Plan (IAPP) is to describe the preferred interim remedial action for addressing the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit and to provide an opportunity for public input into the remedial action selection process.

The Intentional Interim

ERIC Educational Resources Information Center

Nugent, Patricia A.

2011-01-01

The author spent years in central-office administration, most recently in an interim position. Some interim administrators simply see themselves as placeholders until the real deal is hired, giving the organization the opportunity to coast. There are others who see themselves as change agents and cannot wait to undo or redo what their predecessor…

Presidential Transition: The Experience of Two Community College Interim Presidents

ERIC Educational Resources Information Center

Thompson, Matthew D.

2010-01-01

The purpose of this qualitative case study was to understand the experiences of two community college interim presidents, their characteristics, and how they led institutions following an abrupt presidential departure. There were two fundamental questions framing this research study, 1. How do two interim community college presidents lead…

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The... test operation pursuant to § 73.1620, may commence interim hybrid IBOC DAB operation with digital... No. 99-325. FM stations are permitted to operate with hybrid digital effective radiated power equal...

17 CFR 210.10-01 - Interim financial statements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accountant on the review must be filed with the interim financial statements. (e) Filing of other interim... sheets shall include only major captions (i.e., numbered captions) prescribed by the applicable sections... the date of any material accounting change and the reasons for making it. In addition, for filings on...

77 FR 55232 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-03; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0067] Japan Lessons-Learned Project Directorate Interim...-Learned Project Directorate Interim Staff Guidance; issuance. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing the Final Japan Lessons-Learned Project Directorate (JLD...

78 FR 40199 - Draft Spent Fuel Storage and Transportation Interim Staff Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0140] Draft Spent Fuel Storage and Transportation Interim... Spent Fuel Storage and Transportation Interim Staff Guidance No. 24 (SFST-ISG-24), Revision 0, ``The Use of a Demonstration Program as Confirmation of Integrity for Continued Storage of High Burnup Fuel...

75 FR 66553 - Truth in Lending

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... AGENCY: Board of Governors of the Federal Reserve System. ACTION: Interim final rule; request for public comment. SUMMARY: The Board is publishing for public comment an interim final rule amending Regulation Z (Truth in Lending). The interim rule implements Section 129E of the Truth in Lending Act (TILA), which...

Staff Reactions to Interim Leadership in a Student Affairs Organization

ERIC Educational Resources Information Center

Jones, Robin D.

2011-01-01

Interim leadership appointments in higher education are a common strategy used to fill leadership gaps in executive positions. Because student affairs executives are particularly vulnerable to high turnover rates, interim appointments are becoming more widespread. Even with the prevalence of this trend, little attention has been given to the…

Faculty and Student Views of the Interim Term

ERIC Educational Resources Information Center

Centra, John A.; Sobol, Marion G.

1974-01-01

Evaluations of the interim term or 4-1-4 program at various colleges have been generally favorable. A detailed evaluation of the Rider College interim study program based on faculty and student reports indicated that the more nontraditionally oriented courses were rated higher than the more traditional offerings. (Editor/PG)

12 CFR 541.18 - Interim Federal savings association.

Code of Federal Regulations, 2010 CFR

2010-01-01

... an existing savings and loan holding company or to facilitate any other transaction the Office may... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Interim Federal savings association. 541.18... REGULATIONS AFFECTING FEDERAL SAVINGS ASSOCIATIONS § 541.18 Interim Federal savings association. The term...

15 CFR 904.322 - Interim action.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Interim action. 904.322 Section 904... Sanctions and Denials Permit Sanction for Violations § 904.322 Interim action. (a) To protect marine resources during the pendency of an action under this subpart, in cases of willfulness, or as otherwise...

15 CFR 904.322 - Interim action.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Interim action. 904.322 Section 904... Sanctions and Denials Permit Sanction for Violations § 904.322 Interim action. (a) To protect marine resources during the pendency of an action under this subpart, in cases of willfulness, or as otherwise...

Into the Sunset: Reflections of an Interim Administrator.

ERIC Educational Resources Information Center

Marlowe, John

2000-01-01

One advantage to an interim administrative position is that the public cuts short-timers a little slack. Temporary administrators can learn on the job and become experts on specialized subjects. Personnel issues demand more time than interims possess. Such positions usually do not turn into long-term contracts. (MLH)

PCoD Lite - Using an Interim PCoD Protocol to Assess the Effects of Disturbance Associated with US Navy Exercises on Marine Mammal Populations

DTIC Science & Technology

2015-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. PCoD Lite - Using an Interim PCoD Protocol to Assess...US National Research Council (NRC 2005). Here, we provide an insight into how the Interim PCoD approach (Harwood et al. 2014, King et al. 2015...illustrate how the interim PCoD protocol can be used to inform the process of determining whether or not Navy activities are likely to have an impact on

The Na, K-ATPase β-Subunit Isoforms Expression in Glioblastoma Multiforme: Moonlighting Roles

PubMed Central

Rotoli, Deborah; Cejas, Mariana-Mayela; Maeso, María-del-Carmen; Pérez-Rodríguez, Natalia-Dolores; Morales, Manuel; Ávila, Julio

2017-01-01

Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Recent studies point out that gliomas exploit ion channels and transporters, including Na, K-ATPase, to sustain their singular growth and invasion as they invade the brain parenchyma. Moreover, the different isoforms of the β-subunit of Na, K-ATPase have been implicated in regulating cellular dynamics, particularly during cancer progression. The aim of this study was to determine the Na, K-ATPase β subunit isoform subcellular expression patterns in all cell types responsible for microenvironment heterogeneity of GBM using immunohistochemical analysis. All three isoforms, β1, β2/AMOG (Adhesion Molecule On Glia) and β3, were found to be expressed in GBM samples. Generally, β1 isoform was not expressed by astrocytes, in both primary and secondary GBM, although other cell types (endothelial cells, pericytes, telocytes, macrophages) did express this isoform. β2/AMOG and β3 positive expression was observed in the cytoplasm, membrane and nuclear envelope of astrocytes and GFAP (Glial Fibrillary Acidic Protein) negative cells. Interestingly, differences in isoforms expression have been observed between primary and secondary GBM: in secondary GBM, β2 isoform expression in astrocytes was lower than that observed in primary GBM, while the expression of the β3 subunit was more intense. These changes in β subunit isoforms expression in GBM could be related to a different ionic handling, to a different relationship between astrocyte and neuron (β2/AMOG) and to changes in the moonlighting roles of Na, K-ATPase β subunits as adaptor proteins and transcription factors. PMID:29117147

In Search of Teen Dating Violence Typologies.

PubMed

Reidy, Dennis E; Ball, Barbara; Houry, Debra; Holland, Kristin M; Valle, Linda A; Kearns, Megan C; Marshall, Khiya J; Rosenbluth, Barri

2016-02-01

The goal of the present research was to identify distinct latent classes of adolescents that commit teen dating violence (TDV) and assess differences on demographic, behavioral, and attitudinal correlates. Boys and girls (N = 1,149; Mage = 14.3; Grades 6-12) with a history of violence exposure completed surveys assessing six indices of TDV in the preceding 3 months. Indices of TDV included controlling behaviors, psychological TDV, physical TDV, sexual TDV, fear/intimidation, and injury. In addition, adolescents provided demographic and dating history information and completed surveys assessing attitudes condoning violence, relationship skills and knowledge, and reactive/proactive aggression. Latent class analysis indicated a three-class solution wherein the largest class of students was nonviolent on all indices ("nonaggressors") and the smallest class of students demonstrated high probability of nearly all indices of TDV ("multiform aggressors"). In addition, a third class of "emotional aggressors" existed for which there was a high probability of controlling and psychological TDV but low likelihood of any other form of TDV. Multiform aggressors were differentiated from emotional and nonaggressors on the use of self-defense in dating relationships, attitudes condoning violence, and proactive aggression. Emotional aggressors were distinguished from nonaggressors on nearly all measured covariates. Evidence indicates that different subgroups of adolescents engaging in TDV exist. In particular, a small group of youth engaging in multiple forms of TDV can be distinguished from a larger group of youth that commit acts of TDV restricted to emotional aggression (i.e., controlling and psychological) and most youth that do not engage in TDV. Published by Elsevier Inc.

In Search of Teen Dating Violence Typologies

PubMed Central

Reidy, Dennis E.; Ball, Barbara; Houry, Debra; Holland, Kristin M.; Valle, Linda A.; Kearns, Megan C.; Marshall, Khiya J.; Rosenbluth, Barri

2018-01-01

Purpose The goal of the present research was to identify distinct latent classes of adolescents that commit teen dating violence (TDV) and assess differences on demographic, behavioral, and attitudinal correlates. Methods Boys and girls (N = 1,149; Mage = 14.3; Grades 6–12) with a history of violence exposure completed surveys assessing six indices of TDV in the preceding 3 months. Indices of TDV included controlling behaviors, psychological TDV, physical TDV, sexual TDV, fear/intimidation, and injury. In addition, adolescents provided demographic and dating history information and completed surveys assessing attitudes condoning violence, relationship skills and knowledge, and reactive/proactive aggression. Results Latent class analysis indicated a three-class solution wherein the largest class of students was nonviolent on all indices (“nonaggressors”) and the smallest class of students demonstrated high probability of nearly all indices of TDV (“multiform aggressors”). In addition, a third class of “emotional aggressors” existed for which there was a high probability of controlling and psychological TDV but low likelihood of any other form of TDV. Multiform aggressors were differentiated from emotional and nonaggressors on the use of self-defense in dating relationships, attitudes condoning violence, and proactive aggression. Emotional aggressors were distinguished from nonaggressors on nearly all measured covariates. Conclusions Evidence indicates that different subgroups of adolescents engaging in TDV exist. In particular, a small group of youth engaging in multiple forms of TDV can be distinguished from a larger group of youth that commit acts of TDV restricted to emotional aggression (i.e., controlling and psychological) and most youth that do not engage in TDV. PMID:26683984

The Analytic Onion: Examining Training Issues from Different Levels of Analysis. Interim Technical Paper for Period July 1989-June 1991.

ERIC Educational Resources Information Center

Lamb, Theodore A.; Chin, Keric B. O.

This paper proposes a conceptual framework based on different levels of analysis using the metaphor of the layers of an onion to help organize and structure thinking on research issues concerning training. It discusses the core of the "analytic onion," the biological level, and seven levels of analysis that surround that core: the individual, the…

The Similarity of Job Types Reported from Two Independent Analyses of Occupational Data. Interim Report. April 2, 1973-October 12, 1973.

ERIC Educational Resources Information Center

Watson, William J.

Occupational analysts using Comprehensive Occupational Data Analysis Programs (CODAP) make subjective decisions at various stages in their analysis of an occupation. The possibility exists that two different analysts could reach different conclusions in analyzing an occupation, and thereby provide divergent guidance to management. Two analysts,…

Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies

ClinicalTrials.gov

2018-01-30

Advanced or Metastatic Solid Tumours; Breast Cancer; Colorectal Cancer; Gastric Cancer; Cholangiocellular Carcinoma; Ovarian Cancer; Cervical Cancer; Prostate Cancer; Melanoma; Sarcoma; NSCLC; Desmoid Tumour; Adenoid Cystic Carcinoma; Glioblastoma Multiforme; Hodgkin Lymphoma; Non-hodgkin Lymphoma; Multiple Myeloma

Osthole Suppresses the Migratory Ability of Human Glioblastoma Multiforme Cells via Inhibition of Focal Adhesion Kinase-Mediated Matrix Metalloproteinase-13 Expression

PubMed Central

Tsai, Cheng-Fang; Yeh, Wei-Lan; Chen, Jia-Hong; Lin, Chingju; Huang, Shiang-Suo; Lu, Dah-Yuu

2014-01-01

Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. GBM often invades surrounding regions of the brain during its early stages, making successful treatment difficult. Osthole, an active constituent isolated from the dried C. monnieri fruit, has been shown to suppress tumor migration and invasion. However, the effects of osthole in human GBM are largely unknown. Focal adhesion kinase (FAK) is important for the metastasis of cancer cells. Results from this study show that osthole can not only induce cell death but also inhibit phosphorylation of FAK in human GBM cells. Results from this study show that incubating GBM cells with osthole reduces matrix metalloproteinase (MMP)-13 expression and cell motility, as assessed by cell transwell and wound healing assays. This study also provides evidence supporting the potential of osthole in reducing FAK activation, MMP-13 expression, and cell motility in human GBM cells. PMID:24599080

Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zasneda, Sabriani; Widita, Rena

2010-06-22

Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometricalmore » factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.« less

Toroidal-spiral particles for codelivery of anti-VEGFR-2 antibody and irinotecan: a potential implant to hinder recurrence of glioblastoma multiforme.

PubMed

Sharma, Vishal; Köllmer, Melanie; Szymusiak, Magdalena; Nitsche, Ludwig C; Gemeinhart, Richard A; Liu, Ying

2014-03-10

Heterogeneous toroidal-spiral particles (TSPs) were generated by polymer droplet sedimentation, interaction, and cross-linking. TSPs provide a platform for encapsulation and release of multiple compounds of different sizes and physicochemical properties. As a model system, we demonstrate the encapsulation and independently controlled release of an anti-VEGFR-2 antibody and irinotecan for the treatment of glioblastoma multiforme. The anti-VEGFR-2 antibody was released from the TS channels and its binding to HUVECs was confirmed by confocal microscopy and flow cytometry, suggesting active antibody encapsulation and release. Irinotecan, a small molecule drug, was released from the dense polymer matrix of poly(ethylene glycol) diacrylate (MW ~ 700 g/mol; PEGDA 700). Released irinotecan inhibited the proliferation of U251 malignant glioma cells. Since the therapeutic compounds are released through different pathways, specifically diffusion through the polymer matrix versus TS channels, the release rate can be controlled independently through the design of the structure and material of particle components.

Low-dose fotemustine as second-line chemotherapy for recurrent glioblastoma multiforme.

PubMed

De Felice, Francesca; Bulzonetti, Nadia; Musio, Daniela; D'Elia, Alessandro; Salvati, Maurizio; Tombolini, Vincenzo

2013-09-01

To test if fotemustine administrated at low doses during the maintenance phase of gioblastoma therapy could improve the toxicity profile, without reducing progression-free survival at six months (PFS-6). Patients enrolled were affected by recurrent glioblastoma multiforme, proven by magnetic resonance imaging (MRI), at least six months after radiochemotherapy completion. Fotemustine was administered at an induction dose of 100 mg/m(2) followed by a maintenance dose of 75 mg/m(2). All 15 patients completed the induction phase. Eight patients began maintenance-phase therapy and received a median of three cycles (range=2-6). Grade 3 or more haematological toxicity was not documented. The PFS-6 was 5/15 and the median overall survival was 7.5 months. Haematological toxicity compares favourably with trials using the conventional scheme: no grade 3-4 adverse effects were recorded. This low-dose approach could be considered a compromise treatment whilst waiting for definitive standardization of second-line therapy, in order to reduce severe hematological toxicity.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

PubMed

Takanen, Silvia; Bangrazi, Caterina; Caiazzo, Rossella; Raffetto, Nicola; Tombolini, Vincenzo

2013-01-01

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Erythema multiforme associated with contact dermatitis to poison ivy: three cases and a review of the literature.

PubMed

Cohen, L M; Cohen, J L

1998-09-01

Erythema multiforme (EM) is a hypersensitivity reaction that occurs mainly after exposure to certain medications or in the setting of infection, most commonly that due to herpes simplex virus. Rare cases of EM have been reported after allergic contact dermatitis due to various substances. There has been one case in the literature of EM following Rhus contact dermatitis. We report three patients who developed EM after allergic contact dermatitis due to poison ivy. In all three patients, targetoid lesions developed primarily on the palms and soles, either after a brief course of prednisone or during its taper. Two of the patients have had more than one episode of EM after poison ivy dermatitis. Although EM has been described after allergic contact dermatitis due to a variety of antigens (nickel being the most common), there is only one report in the literature of EM following Rhus contact dermatitis. Given the prevalence of allergic contact dermatitis due to poison ivy, this may be an under-reported complication.

Stereotactic intracranial implantation and in vivo bioluminescent imaging of tumor xenografts in a mouse model system of glioblastoma multiforme.

PubMed

Baumann, Brian C; Dorsey, Jay F; Benci, Joseph L; Joh, Daniel Y; Kao, Gary D

2012-09-25

Glioblastoma multiforme (GBM) is a high-grade primary brain cancer with a median survival of only 14.6 months in humans despite standard tri-modality treatment consisting of surgical resection, post-operative radiation therapy and temozolomide chemotherapy. New therapeutic approaches are clearly needed to improve patient survival and quality of life. The development of more effective treatment strategies would be aided by animal models of GBM that recapitulate human disease yet allow serial imaging to monitor tumor growth and treatment response. In this paper, we describe our technique for the precise stereotactic implantation of bio-imageable GBM cancer cells into the brains of nude mice resulting in tumor xenografts that recapitulate key clinical features of GBM. This method yields tumors that are reproducible and are located in precise anatomic locations while allowing in vivo bioluminescent imaging to serially monitor intracranial xenograft growth and response to treatments. This method is also well-tolerated by the animals with low perioperative morbidity and mortality.

MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia–telangiectasia mutated

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Pin; Lan, Jin; Ge, Jianwei

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3′UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer ofmore » GBM. - Highlights: ●miR-26a directly target ATM in GBM cells. ●miR-26a enhances the radiosensitivity of GBM cells. ●miR-26a could reduce the DNA repair capacity of GBM cells.« less

Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

NASA Astrophysics Data System (ADS)

Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

2014-03-01

Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

Glioblastoma multiforme of the brain stem in a patient with acquired immunodeficiency syndrome.

PubMed

Wolff, R; Zimmermann, M; Marquardt, Gerhard; Lanfermann, H; Nafe, R; Seifert, V

2002-09-01

Glioblastoma of the brain stem is rare and there is no description of such a lesion in patients suffering from acquired immunodeficiency syndrome. The majority of intracerebral mass lesions are due either to toxoplasmosis or primary central nervous system lymphomas so that it is usually not included in the differential diagnosis of enhancing lesions of the central nervous system in these patients. A 31-year-old human immunodeficiency virus (HIV) infected man presented with a four months history of slowly progressive deterioration of brainstem associated symptoms despite antitoxoplasmic therapy. Magnetic resonance imaging revealed a large ring enhancing lesion in the brainstem. Clinical and neuroradiological data could not establish a proper diagnosis and a stereotactic serial biopsy was undertaken. Histological examination of the specimen showed a glioblastoma multiforme (GBM) as the first reported case of GBM located in the brainstem in an acquired immunodeficiency syndrome (AIDS) patient. Patient management and effectiveness of stereotactic serial biopsy are discussed.

Subcutaneous tissue metastasis from glioblastoma multiforme: A case report and review of the literature.

PubMed

Frade Porto, Natalia; Delgado Fernández, Juan; García Pallero, María de Los Ángeles; Penanes Cuesta, Juan Ramón; Pulido Rivas, Paloma; Gil Simoes, Ricardo

2018-05-16

Glioblastoma multiforme is the most common primary brain tumor, despite an aggressive clinical course, less than 2% of patients develop extraneural metastasis. We present a 72-year-old male diagnosed with a right temporal glioblastoma due to headache. He underwent total gross resection surgery and after that the patient was treated with adyuvant therapy. Five months after the patient returned with trigeminal neuralgia, and MRI showed an infratemporal cranial mass which infiltrates masticator space, the surrounding bone, the temporal muscle and superior cervical and parotid lymph nodes. The patient underwent a new surgery reaching partial resection of the temporal lesion. After that the patient continued suffering from disabling trigeminal neuralgia, that's why because of the bad clinical situation and the treatment failure we decided to restrict therapeutic efforts. The patient died 3 weeks after the diagnosis of extracranial metastasis. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

p53 regulates the mevalonate pathway in human glioblastoma multiforme

PubMed Central

Laezza, C; D'Alessandro, A; Di Croce, L; Picardi, P; Ciaglia, E; Pisanti, S; Malfitano, A M; Comegna, M; Faraonio, R; Gazzerro, P; Bifulco, M

2015-01-01

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3′-hydroxy-3′-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression. PMID:26469958

From HSV infection to erythema multiforme through autoimmune crossreactivity.

PubMed

Lucchese, Alberta

2018-06-01

Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM. Copyright © 2018 Elsevier B.V. All rights reserved.

The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients.

PubMed

Heimberger, Amy B; Sampson, John H

2009-08-01

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. EGFR variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed in GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon, resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received vaccines targeting EGFRvIII had an unexpectedly long survival time. Further therapeutic strategies and potential pitfalls of using this approach are discussed.

Varicella zoster with erythema multiforme in a young girl: a rare association.

PubMed

Kishore, B Nanda; Ankadavar, Nandini S; Kamath, Ganesh H; Martis, Jacintha

2014-05-01

Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder regarded as a hypersensitivity reaction which is triggered by various factors like infection, drugs, and food. Infectious agents are considered to be a major cause of EM other than idiopathic cause. A young girl presented with fluid-filled lesions all over the body of 3 days duration with history of similar lesions with fever in her sibling 2 weeks prior to admission. This was followed by large fluid-filled lesions with halo 3 days thereafter over the trunk, extremities suggesting target lesions of EM. The diagnosis was confirmed by cytology and positive serology. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence in childhood. VZV as an etiology of EM in a young girl has not been reported so far. This case was reported for its rare association of EM and varicella zoster and also for its rare presentation in a young girl.

Remedy Selection and Land Use at Federal Facilities

EPA Pesticide Factsheets

Analysis of approximately 98 percent of the interim and final source control Records of Decision signed at Federal Facilities on the NPL from the beginning of Superfund through August 1995. PB96-963309. EPA/540/R-96/020. August 1996

75 FR 24957 - Decision to Evaluate a Petition to Designate a Class of Employees From the Los Alamos National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... Laboratory. Location: Los Alamos, New Mexico. Job Titles and/or Job Duties: All employees of the Department.... Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute for...

75 FR 51815 - Decision To Evaluate a Petition To Designate a Class of Employees From the Norton Company...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

..., Massachusetts. Job Titles and/or Job Duties: All employees who worked in any building or area. Period of..., Interim Director, Division of Compensation Analysis and Support, National Institute for Occupational...

Bevacizumab improves survival for patients with advanced cervical cancer

Cancer.gov

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

Bend case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

2000-01-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and aerial photos, gro...

McMinnville case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

1999-12-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed : the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and : aerial photos,...

75 FR 7591 - Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-SFUND-2009-0907; FRL-9114-6] RIN 2050-ZA05 Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites; Extension of... Interim Preliminary Remediation Goals for Dioxin in Soil at Comprehensive Environmental Response...

Do Interim Assessments Reduce the Race and SES Achievement Gaps?

ERIC Educational Resources Information Center

Konstantopoulos, Spyros; Li, Wei; Miller, Shazia R.; van der Ploeg, Arie

2017-01-01

The authors examined differential effects of interim assessments on minority and low socioeconomic status students' achievement in Grades K-6. They conducted a large-scale cluster randomized experiment in 2009-2010 to evaluate the impact of Indiana's policy initiative introducing interim assessments statewide. The authors used 2-level models to…

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

75 FR 54526 - Defense Federal Acquisition Regulation Supplement; Payment of Costs Prior to Definitization...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... in 48 CFR Part 217 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the... interim rule. Therefore, DoD is finalizing the interim rule without change. This rule was not subject to...

76 FR 43260 - Foreign-Trade Zone 72-Indianapolis, IN; Application for Temporary/Interim Manufacturing Authority...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...--Indianapolis, IN; Application for Temporary/Interim Manufacturing Authority; Brevini Wind USA, Inc. (Wind... temporary/interim manufacturing (T/IM) authority within FTZ 72 at the Brevini Wind USA, Inc. (Brevini... requested authority to produce wind turbine gear boxes (HTSUS 8483.40, duty rate: 2.5%). Foreign components...

75 FR 60436 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it is releasing an interim...

75 FR 24667 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it released an interim change...

75 FR 10476 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it released an interim change...

76 FR 776 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it is releasing an interim...

75 FR 15420 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it will release an interim...

76 FR 59119 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it has released an interim...

Can Interim Assessments Be Used for Instructional Change? Policy Brief. RB-51

ERIC Educational Resources Information Center

Goertz, Margaret E.; Olah, Leslie Nabors; Riggan, Matthew

2009-01-01

The purpose of this exploratory study was to examine the use of interim assessments and the policy supports that promote their use to change instruction, focusing on elementary school mathematics. The authors use the term "interim assessments" to refer to assessments that: a) evaluate student knowledge and skills, typically within a…

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2011 CFR

2011-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... 40 Protection of Environment 26 2011-07-01 2011-07-01 false EPA Interim Primary Drinking Water... Water Standards Parameter Maximum level (mg/l) Arsenic 0.05 Barium 1.0 Cadmium 0.01 Chromium 0.05...

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2010 CFR

2010-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... 40 Protection of Environment 25 2010-07-01 2010-07-01 false EPA Interim Primary Drinking Water... Water Standards Parameter Maximum level (mg/l) Arsenic 0.05 Barium 1.0 Cadmium 0.01 Chromium 0.05...

33 CFR 96.360 - Interim Safety Management Certificate: what is it and when can it be used?

Code of Federal Regulations, 2010 CFR

2010-07-01

... section, when— (1) The company's valid Document of Compliance certificate or Interim Document of Compliance certificate applies to that vessel type; (2) The company's safety management system for the vessel... to the responsible person or their company. (b) An Interim Safety Management Certificate is valid for...

76 FR 15028 - Airport Improvement Program (AIP): Interim Policy Regarding Access to Airports From Residential...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... resolution. The goal of the interim policy is to strike a careful balance by accommodating residential... will allow the agency to complete a separate, ongoing general aviation airport study that is analyzing the federally assisted general aviation airport system. The interim policy adopts the changes proposed...

18 CFR 300.20 - Interim acceptance and review of Bonneville Power Administration rates.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Interim acceptance and review of Bonneville Power Administration rates. 300.20 Section 300.20 Conservation of Power and Water... Director of the Office of Energy Market Regulation; or (ii) Deny the Administrator's interim rate request...

42 CFR 417.572 - Budget and enrollment forecast and interim reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Budget and enrollment forecast and interim reports... PLANS, AND HEALTH CARE PREPAYMENT PLANS Medicare Payment: Cost Basis § 417.572 Budget and enrollment forecast and interim reports. (a) Annual submittal. The HMO or CMP must submit an annual operating budget...

78 FR 5830 - Draft Environmental Assessment and Proposed Habitat Conservation Plan for the Interim Operations...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... Operations of PacifiCorp's Klamath Hydroelectric Project on the Klamath River, Klamath County, OR, and... Environmental Policy Act (NEPA) for the interim operations of the Klamath Hydroelectric Project in [[Page 5831... habitats upon which they depend, resulting from the interim operations of the Klamath Hydroelectric Project...

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false EPA Interim Primary Drinking Water Standards III Appendix III to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Pt....

75 FR 65528 - Membership of the National Science Board's Senior Executive Service Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

...: Comments should be addressed to Interim Director, Division of Human Resource Management and Chief Human.... Judith S. Sunley, Interim Director, Division of Human Resource Management and Chief Human Capital Officer..., Interim Director, Division of Human Resource Management and Chief Human Capital Officer. [FR Doc. 2010...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

77 FR 15818 - License Renewal Interim Staff Guidance LR-ISG-2011-05: Ongoing Review of Operating Experience

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...-05: Ongoing Review of Operating Experience AGENCY: Nuclear Regulatory Commission. ACTION: Interim... License Renewal Interim Staff Guidance (LR-ISG), LR-ISG-2011-05, ``Ongoing Review of Operating Experience... industry-wide operating experience as an attribute of aging management programs used at nuclear power...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

Determination of the methylation status of MGMT in different regions within glioblastoma multiforme.

PubMed

Hamilton, Mark G; Roldán, Gloria; Magliocco, Anthony; McIntyre, John B; Parney, Ian; Easaw, Jacob C

2011-04-01

Epigenetic silencing of the MGMT gene through promoter methylation correlates with improved survival in Glioblastoma Multiforme (GBM) patients receiving concurrent chemoradiotherapy. Although the clinical benefit is primarily seen in patients with methylated MGMT promoter, some unmethylated patients also respond to Temozolomide. One possible explanation may be intratumoral heterogeneity. This study was designed to assess the methylation status of the MGMT promoter in different areas of GBM and determine if methylation status varied depending on the fixation technique (paraffin-embedding versus fresh frozen) used to store tissue. Using intraoperative navigation, biopsies were obtained from three distinct regions: the enhancing outer area, the non-enhancing inner core, and an area immediately outside the enhancing region. Only patients with GBM were included for evaluation and analysis. Samples taken from each area were divided with half stored by flash freezing and the other half stored using paraffin fixation. Methylation Specific-PCR (MS-PCR) was used for analysis of MGMT promoter methylation. Thirteen patients were included. Ten were male with a median age of 62 years. In each patient, samples were taken from the enhancing rim and the necrotic centre. However, it was not considered safe or feasible to obtain samples from the area immediately adjacent to the enhancing tumor rim in one case. All patients were homogeneous for methylation status throughout their tumor and tissue taken adjacent to it when frozen tissue was used. However, four patients had discrepancies in the MGMT promoter status between the frozen and paraffin-embedded blocks and one patient was not homogeneous within the tumor when paraffin-embedded tissue was used. MGMT promoter methylation status was homogeneous in all GBM tumors. Our observation that methylation status varied depending if the DNA was extracted from paraffin-embedded versus frozen tissue is concerning. Although the reason for this is unclear, we postulate that the timing from resection to fixation or the process of fixation itself may potentially alter methylation status in paraffin-embedded tumors.

SU-F-T-392: Superior Brainstem and Cochlea Sparing with VMAT for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briere, TM; McAleer, MF; Levy, LB

Purpose: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. Methods: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT. All planning target volumes (PTVs) were prescribed a dose of 50 Gy, with a simultaneous integrated boost to 60more » Gy. Most IMRT plans used 5 non-coplanar beams, while most VMAT plans used 2 coplanar beams. Statistical analysis was performed using Fisher’s exact test or the Wilcoxon-Mann-Whitney rank sum test. Included in the analysis were patient and treatment characteristics as well as the doses to the target volumes and organs at risk. Results: Treatment times for the VMAT plans were reduced by 5 minutes compared with IMRT. The PTV coverage was similar, with at least 95% covered for all plans, while the median boost PTV dose differed by 0.1 Gy between the IMRT and VMAT cohorts. The doses to the brain, optic chiasm, optic nerves and eyes were not significantly different. The mean dose to the brainstem, however, was 9.4 Gy less with VMAT (p<0.001). The dose to the ipsilateral and contralateral cochleae were respectively 19.7 and 9.5 Gy less (p<0.001). Conclusion: Comparison of clinical treatment plans for separate IMRT and VMAT cohorts demonstrates that VMAT can save substantial treatment time while providing similar target coverage and superior sparing of the brainstem and cochleae. To our knowledge this is the first study to demonstrate this benefit of VMAT in the management of GBM.« less

Increasing incidence of glioblastoma multiforme and meningioma, and decreasing incidence of Schwannoma (2000–2008): Findings of a multicenter Australian study

PubMed Central

Dobes, Martin; Khurana, Vini G.; Shadbolt, Bruce; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

2011-01-01

Background: The incidence of primary brain tumors by subtype is currently unknown in Australia. We report an analysis of incidence by tumor subtype in a retrospective multicenter study in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), with a combined population of >7 million with >97% retention rate for medical care. Methods: Data from histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008 were weighted for patient outflow and data completeness, and age standardized and analyzed using joinpoint analysis. Results: A significant increasing incidence in glioblastoma multiforme (GBM) was observed in the study period (annual percentage change [APC], 2.5; 95% confidence interval [CI], 0.4–4.6, n = 2275), particularly after 2006. In GBM patients in the ≥65-year group, a significantly increasing incidence for men and women combined (APC, 3.0; 95% CI, 0.5–5.6) and men only (APC, 2.9; 95% CI, 0.1–5.8) was seen. Rising trends in incidence were also seen for meningioma in the total male population (APC, 5.3; 95% CI, 2.6–8.1, n = 515) and males aged 20–64 years (APC, 6.3; 95% CI, 3.8–8.8). Significantly decreasing incidence trends were observed for Schwannoma for the total study population (APC, –3.5; 95% CI, –7.2 to –0.2, n = 492), significant in women (APC, –5.3; 95% CI, –9.9 to –0.5) but not men. Conclusion: This collection is the most contemporary data on primary brain tumor incidence in Australia. Our registries may observe an increase in malignant tumors in the next few years that they are not detecting now due to late ascertainment. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence by subtype, including the introduction of nonmalignant data collection. PMID:22276231

Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

PubMed Central

Kerkhof, Melissa; Dielemans, Janneke C. M.; van Breemen, Melanie S.; Zwinkels, Hanneke; Walchenbach, Robert; Taphoorn, Martin J.; Vecht, Charles J.

2013-01-01

Background To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. Methods A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months. Results Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7–67.3) compared with 61 weeks (95% CI: 52.5–69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43–0.92; P = .016), adjusting for age, extent of resection, and O6-DNA methylguanine-methyltransferase promoter methylation status. Conclusions Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months’ longer survival of patients with GBM. PMID:23680820

Alpha emitter radium-223 and survival in metastatic prostate cancer.

PubMed

Parker, C; Nilsson, S; Heinrich, D; Helle, S I; O'Sullivan, J M; Fosså, S D; Chodacki, A; Wiechno, P; Logue, J; Seke, M; Widmark, A; Johannessen, D C; Hoskin, P; Bottomley, D; James, N D; Solberg, A; Syndikus, I; Kliment, J; Wedel, S; Boehmer, S; Dall'Oglio, M; Franzén, L; Coleman, R; Vogelzang, N J; O'Bryan-Tear, C G; Staudacher, K; Garcia-Vargas, J; Shan, M; Bruland, Ø S; Sartor, O

2013-07-18

Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

PubMed

Chapman, Paul B; Hauschild, Axel; Robert, Caroline; Haanen, John B; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O'Day, Steven J; Sosman, Jeffrey A; Kirkwood, John M; Eggermont, Alexander M M; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J; Flaherty, Keith T; McArthur, Grant A

2011-06-30

Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

A Conservative Method of Retaining an Interim Obturator for a Total Maxillectomy Patient

PubMed Central

Bettie, Nirmal Famila

2017-01-01

Interim obturators are indicated during the postsurgical phases. It promotes surgical healing and serves as a temporary prosthesis to rehabilitate a patient with intra-oral surgical defect. Retention is gained by wiring, surgical suturing, and other noninvasive methods to enable functional rehabilitation and easy replacement with a permanent obturator. Interim obturators serve as an easy guide for replacing with definitive obturators by indicating prosthesis extensions and the required method of retention. A more conservative and noninvasive method of retaining an interim obturator for a maxillectomy patient is described in this case report. PMID:29284985

A Conservative Method of Retaining an Interim Obturator for a Total Maxillectomy Patient.

PubMed

Bettie, Nirmal Famila

2017-11-01

Interim obturators are indicated during the postsurgical phases. It promotes surgical healing and serves as a temporary prosthesis to rehabilitate a patient with intra-oral surgical defect. Retention is gained by wiring, surgical suturing, and other noninvasive methods to enable functional rehabilitation and easy replacement with a permanent obturator. Interim obturators serve as an easy guide for replacing with definitive obturators by indicating prosthesis extensions and the required method of retention. A more conservative and noninvasive method of retaining an interim obturator for a maxillectomy patient is described in this case report.

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

ClinicalTrials.gov

2018-04-30

Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

7 CFR 1738.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... means the pro forma financial analysis prepared by the applicant, and acceptable to RUS, to determine... years estimated in the feasibility study for completion of the construction covered by the loan... the RE Act to each eligible entity. Interim construction means the construction, improvement, or...

7 CFR 1738.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... means the pro forma financial analysis prepared by the applicant, and acceptable to RUS, to determine... years estimated in the feasibility study for completion of the construction covered by the loan... the RE Act to each eligible entity. Interim construction means the construction, improvement, or...

75 FR 14443 - Decision To Evaluate a Petition To Designate a Class of Employees for Revere Copper and Brass in...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

.... Job Titles and/or Job Duties: Extruders and Shapes Specialists who worked in the Rod and Shape Mill... L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute...

Grants Pass case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

1999-08-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and aerial photos, gro...

40 CFR 265.113 - Closure; time allowed for closure.

Code of Federal Regulations, 2010 CFR

2010-07-01

... includes an amended waste analysis plan, ground-water monitoring and response program, human exposure....113 Section 265.113 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

Land Use Management for Solid Waste Programs

ERIC Educational Resources Information Center

Brown, Sanford M., Jr.

1974-01-01

The author discusses the problems of solid waste disposal and examines various land use management techniques. These include the land use plan, zoning, regionalization, land utilities, and interim use. Information concerning solid waste processing site zoning and analysis is given. Bibliography included. (MA)

Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data

PubMed Central

Araújo, Alex Maurício

2017-01-01

This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area. PMID:28817731

Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data.

PubMed

Espindola, Rafael Luz; Araújo, Alex Maurício

2017-01-01

This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area.

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

49 CFR 37.169 - Interim requirements for over-the-road bus service operated by private entities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Interim requirements for over-the-road bus service... Interim requirements for over-the-road bus service operated by private entities. (a) Private entities operating over-the-road buses, in addition to compliance with other applicable provisions of this part...

76 FR 48197 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... assessable professional reported or required to be reported by a municipal advisor to the MSRB on Form A-11... Assessment and Form A-11- Interim. For purposes of the interim assessment, an assessable professional of a...-Interim as an assessable professional any associated person (i) Who otherwise qualifies as an assessable...

78 FR 53038 - Interim Final Determination to Stay and Defer Sanctions; California; San Joaquin Valley

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R09-OAR-2013-0534; FRL-9900-36-Region 9.... Environmental Protection Agency (EPA). ACTION: Interim final rule. SUMMARY: EPA is making an interim [email protected] . Mail or deliver: Frances Wicher (AIR-2), U.S. Environmental Protection Agency Region 9...

JOINT AND INDIVIDUAL VARIATION EXPLAINED (JIVE) FOR INTEGRATED ANALYSIS OF MULTIPLE DATA TYPES.

PubMed

Lock, Eric F; Hoadley, Katherine A; Marron, J S; Nobel, Andrew B

2013-03-01

Research in several fields now requires the analysis of datasets in which multiple high-dimensional types of data are available for a common set of objects. In particular, The Cancer Genome Atlas (TCGA) includes data from several diverse genomic technologies on the same cancerous tumor samples. In this paper we introduce Joint and Individual Variation Explained (JIVE), a general decomposition of variation for the integrated analysis of such datasets. The decomposition consists of three terms: a low-rank approximation capturing joint variation across data types, low-rank approximations for structured variation individual to each data type, and residual noise. JIVE quantifies the amount of joint variation between data types, reduces the dimensionality of the data, and provides new directions for the visual exploration of joint and individual structure. The proposed method represents an extension of Principal Component Analysis and has clear advantages over popular two-block methods such as Canonical Correlation Analysis and Partial Least Squares. A JIVE analysis of gene expression and miRNA data on Glioblastoma Multiforme tumor samples reveals gene-miRNA associations and provides better characterization of tumor types.

A method for generating new datasets based on copy number for cancer analysis.

PubMed

Kim, Shinuk; Kon, Mark; Kang, Hyunsik

2015-01-01

New data sources for the analysis of cancer data are rapidly supplementing the large number of gene-expression markers used for current methods of analysis. Significant among these new sources are copy number variation (CNV) datasets, which typically enumerate several hundred thousand CNVs distributed throughout the genome. Several useful algorithms allow systems-level analyses of such datasets. However, these rich data sources have not yet been analyzed as deeply as gene-expression data. To address this issue, the extensive toolsets used for analyzing expression data in cancerous and noncancerous tissue (e.g., gene set enrichment analysis and phenotype prediction) could be redirected to extract a great deal of predictive information from CNV data, in particular those derived from cancers. Here we present a software package capable of preprocessing standard Agilent copy number datasets into a form to which essentially all expression analysis tools can be applied. We illustrate the use of this toolset in predicting the survival time of patients with ovarian cancer or glioblastoma multiforme and also provide an analysis of gene- and pathway-level deletions in these two types of cancer.

Interim estimates of the effectiveness of the influenza vaccine against A(H3N2) influenza in adults in South Korea, 2016-2017 season.

PubMed

Noh, Ji Yun; Lim, Sooyeon; Song, Joon Young; Choi, Won Suk; Jeong, Hye Won; Heo, Jung Yeon; Lee, Jacob; Seo, Yu Bin; Lee, Jin-Soo; Wie, Seong Heon; Kim, Young Keun; Park, Kyung Hwa; Jung, Sook-In; Kim, Shin Woo; Lee, Sun Hee; Lee, Han Sol; Yoon, Young Hoon; Cheong, Hee Jin; Kim, Woo Joo

2017-01-01

In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

An Adaptive Staggered Dose Design for a Normal Endpoint.

PubMed

Wu, Joseph; Menon, Sandeep; Chang, Mark

2015-01-01

In a clinical trial where several doses are compared to a control, a multi-stage design that combines both the selection of the best dose and the confirmation of this selected dose is desirable. An example is the two-stage drop-the-losers or pick-the-winner design, where inferior doses are dropped after interim analysis. Selection of target dose(s) can be based on ranking of observed effects, hypothesis testing with adjustment for multiplicity, or other criteria at interim stages. A number of methods have been proposed and have made significant gains in trial efficiency. However, many of these designs started off with all doses with equal allocation and did not consider prioritizing the doses using existing dose-response information. We propose an adaptive staggered dose procedure that allows explicit prioritization of doses and applies error spending scheme that favors doses with assumed better responses. This design starts off with only a subset of the doses and adaptively adds new doses depending on interim results. Using simulation, we have shown that this design performs better in terms of increased statistical power than the drop-the-losers design given strong prior information of dose response.

A two-stage patient enrichment adaptive design in phase II oncology trials.

PubMed

Song, James X

2014-01-01

Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of ERA-Interim precipitation data in complex terrain

NASA Astrophysics Data System (ADS)

Gao, Lu; Bernhardt, Matthias; Schulz, Karsten

2013-04-01

Precipitation controls a large variety of environmental processes, which is an essential input parameter for land surface models e.g. in hydrology, ecology and climatology. However, rain gauge networks provides the necessary information, are commonly sparse in complex terrains, especially in high mountainous regions. Reanalysis products (e.g. ERA-40 and NCEP-NCAR) as surrogate data are increasing applied in the past years. Although they are improving forward, previous studies showed that these products should be objectively evaluated due to their various uncertainties. In this study, we evaluated the precipitation data from ERA-Interim, which is a latest reanalysis product developed by ECMWF. ERA-Interim daily total precipitation are compared with high resolution gridded observation dataset (E-OBS) at 0.25°×0.25° grids for the period 1979-2010 over central Alps (45.5-48°N, 6.25-11.5°E). Wet or dry day is defined using different threshold values (0.5mm, 1mm, 5mm, 10mm and 20mm). The correspondence ratio (CR) is applied for frequency comparison, which is the ratio of days when precipitation occurs in both ERA-Interim and E-OBS dataset. The result shows that ERA-Interim captures precipitation occurrence very well with a range of CR from 0.80 to 0.97 for 0.5mm to 20mm thresholds. However, the bias of intensity increases with rising thresholds. Mean absolute error (MAE) varies between 4.5 mm day-1 and 9.5 mm day-1 in wet days for whole area. In term of mean annual cycle, ERA-Interim almost has the same standard deviation of the interannual variability of daily precipitation with E-OBS, 1.0 mm day-1. Significant wet biases happened in ERA-Interim throughout warm season (May to August) and dry biases in cold season (November to February). The spatial distribution of mean annual daily precipitation shows that ERA-Interim significant underestimates precipitation intensity in high mountains and northern flank of Alpine chain from November to March while pronounced overestimate in the southern flank of Alps. The poor topographical and flow related characteristic representation of ERA-Interim model is possibly responsible for the bias. Particularly, the mountain block effect of moisture is weak captured. The comparison demonstrates that ERA-Interim precipitation intensity needs bias correction for further alpine climate studies, although it reasonably captures precipitation frequency. This critical evaluation not only diagnosed the data quality of ERA-Interim, but also provided the evidence for reanalysis products downscaling and bias correction in complex terrain.

In vitro evaluation of the marginal integrity of CAD/CAM interim crowns.

PubMed

Kelvin Khng, Kwang Yong; Ettinger, Ronald L; Armstrong, Steven R; Lindquist, Terry; Gratton, David G; Qian, Fang

2016-05-01

The accuracy of interim crowns made with computer-aided design and computer-aided manufacturing (CAD/CAM) systems has not been well investigated. The purpose of this in vitro study was to evaluate the marginal integrity of interim crowns made by CAD/CAM compared with that of conventional polymethylmethacrylate (PMMA) crowns. A dentoform mandibular left second premolar was prepared for a ceramic crown and scanned for the fabrication of 60 stereolithical resin dies, half of which were scanned to fabricate 15 Telio CAD-CEREC and 15 Paradigm MZ100-E4D-E4D crowns. Fifteen Caulk and 15 Jet interim crowns were made on the remaining resin dies. All crowns were cemented with Tempgrip under a 17.8-N load, thermocycled for 1000 cycles, placed in 0.5% acid fuschin for 24 hours, and embedded in epoxy resin before sectioning from the mid-buccal to mid-lingual surface. The marginal discrepancy was measured using a traveling microscope, and dye penetration was measured as a percentage of the overall length under the crown. The mean vertical marginal discrepancy of the conventionally made interim crowns was greater than for the CAD/CAM crowns (P=.006), while no difference was found for the horizontal component (P=.276). The mean vertical marginal discrepancy at the facial surface of the Caulk crowns was significantly greater than that of the other 3 types of interim crowns (P<.001). At the facial margin, the mean horizontal component of the Telio crowns was significantly larger than that of the other 3 types, with no difference at the lingual margins (P=.150). The mean percentage dye penetration for the Paradigm MZ100-E4D crowns was significantly greater and for Jet crowns significantly smaller than for the other 3 crowns (P<.001). However, the mean percentage dye penetration was significantly correlated with the vertical and horizontal marginal discrepancies of the Jet interim crowns at the facial surface and with the horizontal marginal discrepancies of the Caulk interim crowns at the lingual surface (P<.01 in each instance). A significantly smaller vertical marginal discrepancy was found with the interim crowns fabricated by CAD/CAM as compared with PMMA crowns; however, this difference was not observed for the horizontal component. The percentage dye penetration was correlated with vertical and horizontal discrepancies at the facial surface for the Jet interim crowns and with horizontal discrepancies at the lingual surface for the Caulk interim crowns. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation

PubMed Central

Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

2014-01-01

Background Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Methods Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine–phosphate–guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Results Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine–phosphate–guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Conclusions Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation–specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. PMID:24997139

MERTK Inhibition Induces Polyploidy and Promotes Cell Death and Cellular Senescence in Glioblastoma Multiforme

PubMed Central

Sufit, Alexandra; Lee-Sherick, Alisa B.; DeRyckere, Deborah; Rupji, Manali; Dwivedi, Bhakti; Varella-Garcia, Marileila; Pierce, Angela M.; Kowalski, Jeanne; Wang, Xiaodong; Frye, Stephen V.; Earp, H. Shelton

2016-01-01

Background MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. Methods Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database. GBM cell lines (A172, SF188, U251) were treated in vitro with increasing doses of UNC2025 (50-400nM). Cell count and viability were determined by trypan blue exclusion. Cell cycle profiles and induction of apoptosis were assessed by flow cytometric analysis after BrdU or Po-Pro-1/propidium iodide staining, respectively. Polyploidy was detected by propidium iodide staining and metaphase spread. Cellular senescence was determined by β-galactosidase staining and senescence-associated secretory cytokine analysis. Results Decreased overall survival significantly correlated with high levels of GAS6 expression in GBM, highlighting the importance of TAM kinase signaling in GBM tumorigenesis and/or therapy resistance and providing strong rationale for targeting these pathways in the clinic. All three GBM cell lines exhibited dose dependent reductions in cell number and colony formation (>90% at 200nM) after treatment with UNC2025. Cell cycle analysis demonstrated accumulation of cells in the G2/M phase and development of polyploidy. After extended exposure, 60–80% of cells underwent apoptosis. The majority of surviving cells (65–95%) were senescent and did not recover after drug removal. Thus, UNC2025 mediates anti-tumor activity in GBM by multiple mechanisms. Conclusions The findings described here provide further evidence of oncogenic roles for MERTK in GBM, demonstrate the importance of kinase activity for MERTK tumorigenicity and validate UNC2025, a novel MERTK inhibitor, as a potential therapeutic agent for treatment of GBM. PMID:27783662

Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

PubMed

Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

2010-01-01

To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

How well do we know the global water cycle? - Intercomparison and Performance Analysis of the Hydrological Cycle in Three State-of-the-Art Reanalyses

NASA Astrophysics Data System (ADS)

Kunstmann, H.; Lorenz, C.

2012-12-01

The three state-of-the-art global atmospheric reanalysis models—namely, ECMWF Interim Re-Analysis (ERA-Interim), Modern-Era Retrospective Analysis for Research and Applications (MERRA; NASA), and Climate Forecast System Reanalysis (CFSR; NCEP)—are analyzed and compared with independent observations (GPCC; GPCP; CRU; CPC; DEL; HOAPS) in the period between 1989 and 2006. Comparison of precipitation and temperature estimates from the three models with gridded observations reveals large differences between the reanalyses and also of the observation datasets. A major source of uncertainty in the observations is the spatial distribution and change of the number of gauges over time. In South America for example, active measuring stations were reduced from 4267 to 390. The quality of precipitation estimates from the reanalyses strongly depends on the geographic location, as there are significant differences especially in tropical regions. The closure of the water cycle in the three reanalyses is analyzed by estimating long-term mean values for precipitation, evapotranspiration, surface runoff, and moisture flux divergence. Major shortcomings in the moisture budgets of the datasets are mainly due to inconsistencies of the net precipitation minus evaporation and evapotranspiration, respectively, (P-E) estimates over the oceans and landmasses. This imbalance largely originates from the assimilation of radiance sounding data from the NOAA-15 satellite, which results in an unrealistic increase of oceanic P-E in the MERRA and CFSR budgets. Overall, ERA-Interim shows both a comparatively reasonable closure of the terrestrial and atmospheric water balance and a reasonable agreement with the observation datasets. The limited performance of the three state-of-the-art reanalyses in reproducing the hydrological cycle, however, puts the use of these models for climate trend analyses and long-term water budget studies into question.

Elimination of exemptions for chemical mixtures containing the list I chemicals ephedrine and/or pseudoephedrine. Final rule.

PubMed

2008-07-10

The Drug Enforcement Administration (DEA) is finalizing, without change, the Interim Rule with Request for Comment published in the Federal Register on July 25, 2007 (72 FR 40738). The Interim Rule removed the Controlled Substances Act (CSA) exemptions for chemical mixtures containing ephedrine and/or pseudoephedrine with concentration limits at or below five percent. Upon the effective date of the Interim Rule, all ephedrine and pseudoephedrine chemical mixtures, regardless of concentration and form, became subject to the regulatory provisions of the CSA. DEA regulated the importation, exportation, manufacture, and distribution of these chemical mixtures by requiring persons who handle these chemical mixtures to register with DEA, maintain certain records common to business practice, and file certain reports, regarding these chemical mixtures. No comments to the Interim Rule were received. This Final Rule finalizes the Interim Rule without change.

Certification and verification for Northrup Model NSC-01-0732 Fresnel lens concentrating solar collector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1979-03-01

The certification and verification of the Northrup Model NSC-01-0732 Fresnel lens tracking solar collector are presented. A certification statement is included with signatures and a separate report on the structural analysis of the collector system. System verification against the Interim Performance Criteria are indicated by matrices with verification discussion, analysis, and enclosed test results.

Hybrid Wing-Body (HWB) Pressurized Fuselage Modeling, Analysis, and Design for Weight Reduction

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivek

2012-01-01

This paper describes the interim progress for an in-house study that is directed toward innovative structural analysis and design of next-generation advanced aircraft concepts, such as the Hybrid Wing-Body (HWB) and the Advanced Mobility Concept-X flight vehicles, for structural weight reduction and associated performance enhancement. Unlike the conventional, skin-stringer-frame construction for a cylindrical fuselage, the box-type pressurized fuselage panels in the HWB undergo significant deformation of the outer aerodynamic surfaces, which must be minimized without significant structural weight penalty. Simple beam and orthotropic plate theory is first considered for sizing, analytical verification, and possible equivalent-plate analysis with appropriate simplification. By designing advanced composite stiffened-shell configurations, significant weight reduction may be possible compared with the sandwich and ribbed-shell structural concepts that have been studied previously. The study involves independent analysis of the advanced composite structural concepts that are presently being developed by The Boeing Company for pressurized HWB flight vehicles. High-fidelity parametric finite-element models of test coupons, panels, and multibay fuselage sections, were developed for conducting design studies and identifying critical areas of potential failure. Interim results are discussed to assess the overall weight/strength advantages.

40 CFR 52.243 - Interim approval of the Carbon Monoxide plan for the South Coast.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Interim approval of the Carbon Monoxide plan for the South Coast. 52.243 Section 52.243 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.243 Interim approval of the Carbon...

49 CFR 1152.29 - Prospective use of rights-of-way for interim trail use and rail banking.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Prospective use of rights-of-way for interim trail... Governing Notice, Applications, Financial Assistance, Acquisition for Public Use, and Trail Use § 1152.29 Prospective use of rights-of-way for interim trail use and rail banking. (a) If any state, political...

Temps at the Top: Factors Related to the Appointment of Interim Community College Presidents

ERIC Educational Resources Information Center

Goff, Susan L.

2012-01-01

The appointment of interim community college presidents, the topic of this study, is a little understood phenomenon. A growing shortage of community college presidents coupled with a lack of replacements suggests the appointment of interims will continue well into the future. This study, with a purpose of looking at the factors related to the…

Office of Inspector General; Medicare and state health care programs: fraud and abuse; issuance of advisory opinions by the OIG. Final rule.

PubMed

2008-07-17

OIG is adopting in final form, without change, an interim final rule published on March 26, 2008 (73 FR 15937). We received no comments to the interim final rule. The interim final rule revised the process for advisory opinion requestors to submit payments for advisory opinion costs.

From Testing to Teaching: The Use of Interim Assessments in Classroom Instruction. CPRE Research Report # RR-65

ERIC Educational Resources Information Center

Goertz, Margaret E.; Olah, Leslie Nabors; Riggan, Matthew

2009-01-01

The purpose of this exploratory study is to examine the use of interim assessments and the policy supports that promote use to improve instruction, focusing on elementary school mathematics. The authors use the term "interim assessments" to refer to assessments that a) evaluate student knowledge and skills, typically within a limited…

40 CFR 52.243 - Interim approval of the Carbon Monoxide plan for the South Coast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Interim approval of the Carbon Monoxide plan for the South Coast. 52.243 Section 52.243 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.243 Interim approval of the Carbon...

40 CFR 52.243 - Interim approval of the Carbon Monoxide plan for the South Coast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Interim approval of the Carbon Monoxide plan for the South Coast. 52.243 Section 52.243 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.243 Interim approval of the Carbon...

40 CFR 52.243 - Interim approval of the Carbon Monoxide plan for the South Coast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Interim approval of the Carbon Monoxide plan for the South Coast. 52.243 Section 52.243 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.243 Interim approval of the Carbon...

76 FR 5564 - Grant of Interim Extension of the Term of U.S. Patent No. 4,971,802; MIFAMURTIDE

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-01

... DEPARTMENT OF COMMERCE Patent and Trademark Office [Docket No. PTO-P-2011-0001] Grant of Interim... Office, Commerce. ACTION: Notice of interim patent term extension. SUMMARY: The United States Patent and... States Patent and Trademark Office. [FR Doc. 2011-2088 Filed 1-31-11; 8:45 am] BILLING CODE 3510-16-P ...

Interim Testing, Socio-Economic Status, and the Odds of Passing Grade 8 State Tests in New Jersey

ERIC Educational Resources Information Center

Babo, Gerard; Tienken, Christopher H.; Gencarelli, Maria A.

2014-01-01

A review of the literature pertaining to the effect and influence of commercially-prepared interim assessments in mathematics and language arts literacy reveals a lack of quantitative data to determine the value of these products for school reform. This study examined the ability of commercially-prepared interim pretest and posttest assessments in…

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... shall set interim transport and termination rates either at the default ceilings specified in § 51.705(c) or in accordance with a bill-and-keep methodology as defined in § 51.713. (3) In a state in which the... minute of use), and transport (as described in § 51.707(b)(2)). (c) An interim arrangement shall cease to...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... shall set interim transport and termination rates either at the default ceilings specified in § 51.705(c) or in accordance with a bill-and-keep methodology as defined in § 51.713. (3) In a state in which the... minute of use), and transport (as described in § 51.707(b)(2)). (c) An interim arrangement shall cease to...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... shall set interim transport and termination rates either at the default ceilings specified in § 51.705(c) or in accordance with a bill-and-keep methodology as defined in § 51.713. (3) In a state in which the... minute of use), and transport (as described in § 51.707(b)(2)). (c) An interim arrangement shall cease to...

77 FR 34399 - Public Housing Assessment System (PHAS): Capital Fund Interim Scoring Notice; Request for Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

...-indicator of the Capital Fund indicator to all PHAs for the Capital Fund Indicator under the PHAS interim... transition to the scoring system implemented by the PHAS interim rule, especially as relates to the indicator that assesses occupancy rate. The 5 points for the occupancy sub-indicator will be awarded for fiscal...

Fabrication of an interim complete removable dental prosthesis with an in-office digital light processing three-dimensional printer: A proof-of-concept technique.

PubMed

Lin, Wei-Shao; Harris, Bryan T; Pellerito, John; Morton, Dean

2018-04-30

This report describes a proof of concept for fabricating an interim complete removable dental prosthesis with a digital light processing 3-dimensional (3D) printer. Although an in-office 3D printer can reduce the overall production cost for an interim complete removable dental prosthesis, the process has not been validated with clinical studies. This report provided a preliminary proof of concept in developing a digital workflow for the in-office additively manufactured interim complete removable dental prosthesis. Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Neuro-Oncology Branch (NOB), Center for Cancer Research (CCR), National Cancer Institute (NCI) of the National Institutes of Health (NIH) is seeking outstanding postdoctoral candidates interested in studying the metabolic changes in brain tumors such as glioblastoma multiforme (GBMs).  NOB’s Metabolomics program is interested in revealing the metabolic alterations of

Measuring Preschool Cognitive Growth while It's Still Happening: The Learning Express

ERIC Educational Resources Information Center

McDermott, Paul A.; Fantuzzo, John W.; Waterman, Clare; Angelo, Lauren E.; Warley, Heather P.; Gadsden, Vivian L.; Zhang, Xiuyuan

2009-01-01

Educators need accurate assessments of preschool cognitive growth to guide curriculum design, evaluation, and timely modification of their instructional programs. But available tests do not provide content breadth or growth sensitivity over brief intervals. This article details evidence for a multiform, multiscale test criterion-referenced to…

7 CFR 1737.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... Feasibility study means the pro forma financial analysis performed by RUS to determine the economic... RUS to the borrower's construction fund. Borrower means any organization which has an outstanding loan... percent per year. Initial loan means the first loan made to a borrower. Interim construction means the...

7 CFR 1737.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... Feasibility study means the pro forma financial analysis performed by RUS to determine the economic... RUS to the borrower's construction fund. Borrower means any organization which has an outstanding loan... percent per year. Initial loan means the first loan made to a borrower. Interim construction means the...

7 CFR 1737.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... Feasibility study means the pro forma financial analysis performed by RUS to determine the economic... RUS to the borrower's construction fund. Borrower means any organization which has an outstanding loan... percent per year. Initial loan means the first loan made to a borrower. Interim construction means the...

7 CFR 1737.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... Feasibility study means the pro forma financial analysis performed by RUS to determine the economic... RUS to the borrower's construction fund. Borrower means any organization which has an outstanding loan... percent per year. Initial loan means the first loan made to a borrower. Interim construction means the...

7 CFR 1737.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... Feasibility study means the pro forma financial analysis performed by RUS to determine the economic... RUS to the borrower's construction fund. Borrower means any organization which has an outstanding loan... percent per year. Initial loan means the first loan made to a borrower. Interim construction means the...

Aeromedical Airlift -- Do the Pieces Fit?

DTIC Science & Technology

1988-01-01

architecture analysis. feasibility study, and system design phase. To save money and time associated with unforeseen down-line modifications that may... loand Redietribution of Patients in CONUS. Draft Interim; Report No. IX-h. Maximnus, Inc., McLean Va.: Prepared for Office of the Assistant.Secretary of

78 FR 10269 - National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... agencies incur the remaining costs. Abbreviations Used in This Document AGI--Acute Gastrointestinal Illness AIDS--Acquired Immune Deficiency Syndrome AIP--Agreement in Principle AWWA--American Water Works... Analysis HUS--Hemolytic Uremic Syndrome ICR--Information Collection Request IESWTR--Interim Enhanced...

IVHS Countermeasures For Rear-End Collisions, Task 1 Volume V: 1985 Nass Case Analysis, Interim Report

DOT National Transportation Integrated Search

1994-02-01

THE ATTACHED REPORT IS FROM THE NHTSA SPONSORED PROGRAM, "IVHS COUNTERMEASURES FOR REAR-END COLLISIONS," CONTRACT #DTNH22-93-C-07326. THE PROGRAM'S PRIMARY OBJECTIVE IS TO DEVELOP PRACTICAL PERFORMANCE GUIDELINES OR SPECIFICATIONS FOR REAR-END COLLIS...

76 FR 38719 - Interim Notice of Funding Availability for the Department of Transportation's National...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... emissions, (applicants are encouraged to provide quantitative information regarding expected reductions in...). Applicants are encouraged to provide quantitative information that validates the existence of substantial... infrastructure investments on systematic analysis of expected benefits and costs, including both quantitative and...

EasyKSORD: A Platform of Keyword Search Over Relational Databases

NASA Astrophysics Data System (ADS)

Peng, Zhaohui; Li, Jing; Wang, Shan

Keyword Search Over Relational Databases (KSORD) enables casual users to use keyword queries (a set of keywords) to search relational databases just like searching the Web, without any knowledge of the database schema or any need of writing SQL queries. Based on our previous work, we design and implement a novel KSORD platform named EasyKSORD for users and system administrators to use and manage different KSORD systems in a novel and simple manner. EasyKSORD supports advanced queries, efficient data-graph-based search engines, multiform result presentations, and system logging and analysis. Through EasyKSORD, users can search relational databases easily and read search results conveniently, and system administrators can easily monitor and analyze the operations of KSORD and manage KSORD systems much better.

Image guidance improves localization of sonographically occult colorectal liver metastases

NASA Astrophysics Data System (ADS)

Leung, Universe; Simpson, Amber L.; Adams, Lauryn B.; Jarnagin, William R.; Miga, Michael I.; Kingham, T. Peter

2015-03-01

Assessing the therapeutic benefit of surgical navigation systems is a challenging problem in image-guided surgery. The exact clinical indications for patients that may benefit from these systems is not always clear, particularly for abdominal surgery where image-guidance systems have failed to take hold in the same way as orthopedic and neurosurgical applications. We report interim analysis of a prospective clinical trial for localizing small colorectal liver metastases using the Explorer system (Path Finder Technologies, Nashville, TN). Colorectal liver metastases are small lesions that can be difficult to identify with conventional intraoperative ultrasound due to echogeneity changes in the liver as a result of chemotherapy and other preoperative treatments. Interim analysis with eighteen patients shows that 9 of 15 (60%) of these occult lesions could be detected with image guidance. Image guidance changed intraoperative management in 3 (17%) cases. These results suggest that image guidance is a promising tool for localization of small occult liver metastases and that the indications for image-guided surgery are expanding.

National School Lunch Program and School Breakfast Program: Nutrition Standards for All Foods Sold in School as Required by the Healthy, Hunger-Free Kids Act of 2010. Final rule and interim final rule.

PubMed

2016-07-29

This rule adopts as final, with some modifications, the National School Lunch Program and School Breakfast Program regulations set forth in the interim final rule published in the Federal Register on June 28, 2013. The requirements addressed in this rule conform to the provisions in the Healthy, Hunger-Free Kids Act of 2010 regarding nutrition standards for all foods sold in schools, other than food sold under the lunch and breakfast programs. Most provisions of this final rule were implemented on July 1, 2014, a full year subsequent to publication of the interim final rule. This was in compliance with section 208 of the Healthy, Hunger-Free Kids Act of 2010, which required that State and local educational agencies have at least one full school year from the date of publication of the interim final rule to implement the competitive food provisions. Based on comments received on the interim final rule and implementation experience, this final rule makes a few modifications to the nutrition standards for all foods sold in schools implemented on July 1, 2014. In addition, this final rule codifies specific policy guidance issued after publication of the interim rule. Finally, this rule retains the provision related to the standard for total fat as interim and requests further comment on this single standard.

Analysis of Commercially Available Firefighting Helmet and Boot Options for the Joint Firefighter Integrated Response Ensemble (JFIRE)

DTIC Science & Technology

2012-02-01

AFRL-RX-TY-TR-2012-0022 ANALYSIS OF COMMERCIALLY AVAILABLE HELMET AND BOOT OPTIONS FOR THE JOINT FIREFIGHTER INTEGRATED RESPONSE ENSEMBLE...Interim Technical Report 01-SEP-2010 -- 31-JAN-2011 Analysis of Commercially Available Firefighting Helmet and Boot Options for the Joint Firefighter...ensemble. A requirements correlation matrix was generated and sent to industry detailing objective and threshold measurements for both the helmet

WWC Review of the Report "The Impact of Indiana's System of Interim Assessments on Mathematics and Reading." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

The study, "The Impact of Indiana's System of Interim Assessments on Mathematics and Reading," examined the effects of using Diagnostic Assessment Tools (DAT) on mathematics and reading outcomes for students in 59 Indiana schools during the 2009-10 academic year. DAT consists of interim assessment tools--Wireless Generation's mCLASS for…

The Predictive Validity of Interim Assessment Scores Based on the Full-Information Bifactor Model for the Prediction of End-of-Grade Test Performance

ERIC Educational Resources Information Center

Immekus, Jason C.; Atitya, Ben

2016-01-01

Interim tests are a central component of district-wide assessment systems, yet their technical quality to guide decisions (e.g., instructional) has been repeatedly questioned. In response, the study purpose was to investigate the validity of a series of English Language Arts (ELA) interim assessments in terms of dimensionality and prediction of…

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

Differentially expressed proteins in glioblastoma multiforme identified with a nanobody-based anti-proteome approach and confirmed by OncoFinder as possible tumor-class predictive biomarker candidates

PubMed Central

Jovčevska, Ivana; Zupanec, Neja; Urlep, Žiga; Vranič, Andrej; Matos, Boštjan; Stokin, Clara Limbaeck; Muyldermans, Serge; Myers, Michael P.; Buzdin, Anton A.; Petrov, Ivan; Komel, Radovan

2017-01-01

Glioblastoma multiforme is the most frequent primary malignancy of the central nervous system. Despite remarkable progress towards an understanding of tumor biology, there is no efficient treatment and patient outcome remains poor. Here, we present a unique anti-proteomic approach for selection of nanobodies specific for overexpressed glioblastoma proteins. A phage-displayed nanobody library was enriched in protein extracts from NCH644 and NCH421K glioblastoma cell lines. Differential ELISA screenings revealed seven nanobodies that target the following antigens: the ACTB/NUCL complex, VIM, NAP1L1, TUFM, DPYSL2, CRMP1, and ALYREF. Western blots showed highest protein up-regulation for ALYREF, CRMP1, and VIM. Moreover, bioinformatic analysis with the OncoFinder software against the complete “Cancer Genome Atlas” brain tumor gene expression dataset suggests the involvement of different proteins in the WNT and ATM pathways, and in Aurora B, Sem3A, and E-cadherin signaling. We demonstrate the potential use of NAP1L1, NUCL, CRMP1, ACTB, and VIM for differentiation between glioblastoma and lower grade gliomas, with DPYSL2 as a promising “glioma versus reference” biomarker. A small scale validation study confirmed significant changes in mRNA expression levels of VIM, DPYSL2, ACTB and TRIM28. This work helps to fill the information gap in this field by defining novel differences in biochemical profiles between gliomas and reference samples. Thus, selected genes can be used to distinguish glioblastoma from lower grade gliomas, and from reference samples. These findings should be valuable for glioblastoma patients once they are validated on a larger sample size. PMID:28498803

Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival

PubMed Central

Herzog, Susann; Fink, Matthias Alexander; Weitmann, Kerstin; Friedel, Claudius; Hadlich, Stefan; Langner, Sönke; Kindermann, Katharina; Holm, Tobias; Böhm, Andreas; Eskilsson, Eskil; Miletic, Hrvoje; Hildner, Markus; Fritsch, Michael; Vogelgesang, Silke; Havemann, Christoph; Ritter, Christoph Alexander; Meyer zu Schwabedissen, Henriette Elisabeth; Rauch, Bernhard; Hoffmann, Wolfgang; Kroemer, Heyo Klaus; Schroeder, Henry; Bien-Möller, Sandra

2015-01-01

Background The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy. Methods Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways. Results In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins. Conclusions Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM. PMID:25155357

FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.

PubMed

Durmaz, Arda; Henderson, Tim A D; Brubaker, Douglas; Bebek, Gurkan

2017-01-01

Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies. In this study we present an integrative omics approach to group patients based on their altered pathway characteristics and show prognostic differences within breast cancer (p < 9:57E - 10) and glioblastoma multiforme (p < 0:05) patients. We were able validate this approach in secondary RNA-Seq datasets with p < 0:05 and p < 0:01 respectively. We also performed pathway enrichment analysis to further investigate the biological relevance of dysregulated pathways. We compared our approach with network-based classifier algorithms and showed that our unsupervised approach generates more robust and biologically relevant clustering whereas previous approaches failed to report specific functions for similar patient groups or classify patients into prognostic groups. These results could serve as a means to improve prognosis for future cancer patients, and to provide opportunities for improved treatment options and personalized interventions. The proposed novel graph mining approach is able to integrate PPI networks with gene expression in a biologically sound approach and cluster patients in to clinically distinct groups. We have utilized breast cancer and glioblastoma multiforme datasets from microarray and RNA-Seq platforms and identified disease mechanisms differentiating samples. Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/dysprog.

Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.

Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dosemore » at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.« less

Comparative proteomics as a tool for identifying specific alterations within interferon response pathways in human glioblastoma multiforme cells

PubMed Central

Lobas, Anna A; Solovyeva, Elizaveta M; Sidorenko, Alena S; Gorshkov, Vladimir; Kjeldsen, Frank; Bubis, Julia A; Ivanov, Mark V; Ilina, Irina Y; Moshkovskii, Sergei A; Chumakov, Peter M; Gorshkov, Mikhail V

2018-01-01

An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where oncolytic virus therapy would be most effective. We quantified changes in protein abundances in two glioblastoma multiforme (GBM) cell lines that differ in the ability to induce resistance to vesicular stomatitis virus (VSV) infection in response to type I interferon (IFN) treatment. In IFN-treated samples we observed an up-regulation of protein products of some IFN-regulated genes (IRGs). In total, the proteome analysis revealed up to 20% more proteins encoded by IRGs in the glioblastoma cell line, which develops resistance to VSV infection after pre-treatment with IFN. In both cell lines protein-protein interaction and signaling pathway analyses have revealed a significant stimulation of processes related to type I IFN signaling and defense responses to viruses. However, we observed a deficiency in STAT2 protein in the VSV-sensitive cell line that suggests a de-regulation of the JAK/STAT/IRF9 signaling. The study has shown that the up-regulation of IRG proteins induced by the IFNα treatment of GBM cells can be detected at the proteome level. Similar analyses could be applied for revealing functional alterations within the antiviral mechanisms in glioblastoma samples, accompanying by acquisition of sensitivity to oncolytic viruses. The approach can be useful for discovering the biomarkers that predict a potential sensitivity of individual glioblastoma tumors to oncolytic virus therapy. PMID:29416731

Integrative analysis of micro-RNA, gene expression, and survival of glioblastoma multiforme.

PubMed

Huang, Yen-Tsung; Hsu, Thomas; Kelsey, Karl T; Lin, Chien-Ling

2015-02-01

Glioblastoma multiforme (GBM), the most common type of malignant brain tumor, is highly fatal. Limited understanding of its rapid progression necessitates additional approaches that integrate what is known about the genomics of this cancer. Using a discovery set (n = 348) and a validation set (n = 174) of GBM patients, we performed genome-wide analyses that integrated mRNA and micro-RNA expression data from GBM as well as associated survival information, assessing coordinated variability in each as this reflects their known mechanistic functions. Cox proportional hazards models were used for the survival analyses, and nonparametric permutation tests were performed for the micro-RNAs to investigate the association between the number of associated genes and its prognostication. We also utilized mediation analyses for micro-RNA-gene pairs to identify their mediation effects. Genome-wide analyses revealed a novel pattern: micro-RNAs related to more gene expressions are more likely to be associated with GBM survival (P = 4.8 × 10(-5)). Genome-wide mediation analyses for the 32,660 micro-RNA-gene pairs with strong association (false discovery rate [FDR] < 0.01%) identified 51 validated pairs with significant mediation effect. Of the 51 pairs, miR-223 had 16 mediation genes. These 16 mediation genes of miR-223 were also highly associated with various other micro-RNAs and mediated their prognostic effects as well. We further constructed a gene signature using the 16 genes, which was highly associated with GBM survival in both the discovery and validation sets (P = 9.8 × 10(-6)). This comprehensive study discovered mediation effects of micro-RNA to gene expression and GBM survival and provided a new analytic framework for integrative genomics. © 2014 WILEY PERIODICALS, INC.

Iridium-Knife: Another knife in radiation oncology.

PubMed

Milickovic, Natasa; Tselis, Nikolaos; Karagiannis, Efstratios; Ferentinos, Konstantinos; Zamboglou, Nikolaos

Intratarget dose escalation with superior conformity is a defining feature of three-dimensional (3D) iridium-192 ( 192 Ir) high-dose-rate (HDR) brachytherapy (BRT). In this study, we analyzed the dosimetric characteristics of interstitial 192 Ir HDR BRT for intrathoracic and cerebral malignancies. We examined the dose gradient sharpness of HDR BRT compared with that of linear accelerator-based stereotactic radiosurgery and stereotactic body radiation therapy, usually called X-Knife, to demonstrate that it may as well be called a Knife. Treatment plans for 10 patients with recurrent glioblastoma multiforme or intrathoracic malignancies, five of each entity, treated with X-Knife (stereotactic radiosurgery for glioblastoma multiforme and stereotactic body radiation therapy for intrathoracic malignancies) were replanned for simulated HDR BRT. For 3D BRT planning, we used identical structure sets and dose prescription as for the X-Knife planning. The indices for qualitative treatment plan analysis encompassed planning target volume coverage, conformity, dose falloff gradient, and the maximum dose-volume limits to different organs at risk. Volume coverage in HDR plans was comparable to that calculated for X-Knife plans with no statistically significant difference in terms of conformity. The dose falloff gradient-sharpness-of the HDR plans was considerably steeper compared with the X-Knife plans. Both 3D 192 Ir HDR BRT and X-Knife are effective means for intratarget dose escalation with HDR BRT achieving at least equal conformity and a steeper dose falloff at the target volume margin. In this sense, it can reasonably be argued that 3D 192 Ir HDR BRT deserves also to be called a Knife, namely Iridium-Knife. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

PubMed

Jung, Yuchae; Park, Heejoo; Zhao, Hui-Yuan; Jeon, Raok; Ryu, Jae-Ha; Kim, Woo-Young

2014-07-01

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFβ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis.

PubMed

Server, Andrés; Orheim, Tone E Døli; Graff, Bjørn A; Josefsen, Roger; Kumar, Theresa; Nakstad, Per H

2011-05-01

Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region.

Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme

PubMed Central

Rosati, Anna; Poliani, Pietro Luigi; Todeschini, Alice; Cominelli, Manuela; Medicina, Daniela; Cenzato, Marco; Simoncini, Edda Lucia; Magrini, Stefano Maria; Buglione, Michela; Grisanti, Salvatore; Padovani, Alessandro

2013-01-01

Abstract Background Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival. Methods We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression. Results Median age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5–58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O6-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses. Conclusions Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM. PMID:23410662

IVHS Countermeasures For Rear-End Collisions, Task 1 Volume Iii: 1991 Nass Cds Case Analysis, Interim Report

DOT National Transportation Integrated Search

1994-02-01

THE ATTACHED REPORT IS FROM THE NHTSA SPONSORED PROGRAM, "IVHS COUNTERMEASURES FOR REAR-END COLLISIONS," CONTRACT #DTNH22-93-C-07326. THE PROGRAM'S PRIMARY OBJECTIVE IS TO DEVELOP PRACTICAL PERFORMANCE GUIDELINES OR SPECIFICATIONS FOR REAR-END COLLIS...

Transportation Systems Center Bibliography of Technical Reports, July 1970 - December 1976,

DTIC Science & Technology

1977-04-01

Systems Center. AD-733-763 Judith Gertler, Herbert Glynn, Vivian Hobbs, Frederick Interim Report. June 1971. 16p. Woolfall. AD-733-764 Air Traffic Control...of Deployment Cost Analysis .. .......... FAA-76-20 Airspace Control Environmnent Simulator - Final Report.... ............ .. TSC-131.3 *All- Wether

Locomotive cab design development. volume III: design application analysis - Interim report

DOT National Transportation Integrated Search

1976-10-01

In Volume II of this service of reports on Locomotive Cab Design Development, changes were recommended in the layout and equipment content of locomotive cabs. This report studies the impact of these changes on the interface of the cab with the rest o...

Temporal variability in wind-wave climate and its validation with ESSO-NIOT wave atlas for the head Bay of Bengal

NASA Astrophysics Data System (ADS)

Patra, Anindita; Bhaskaran, Prasad K.

2017-08-01

The head Bay region bordering the northern Bay of Bengal is a densely populated area with a complex geomorphologic setting, and highly vulnerable to extreme water levels along with other factors like sea level rise and impact of tropical cyclones. The influence of climate change on wind-wave regime from this region of Bay of Bengal is not known well and that requires special attention, and there is a need to perform its long-term assessment for societal benefits. This study provides a comprehensive analysis on the temporal variability in domain averaged wind speed, significant wave height (SWH) utilizing satellite altimeter data (1992-2012) and mean wave period using ECMWF reanalysis products ERA-Interim (1992-2012) and ERA-20C (1992-2010) over this region. The SWH derived from WAVEWATCH III (WW3) model along with the ERA-Interim reanalysis supplements the observed variability in satellite altimeter observations. Further, the study performs an extensive error estimation of SWH and mean wave period with ESSO-NIOT wave atlas that shows a high degree of under-estimation in the wave atlas mean wave period. Annual mean and wind speed maxima from altimeter show an increasing trend, and to a lesser extent in the SWH. Interestingly, the estimated trend is higher for maxima compared to the mean conditions. Analysis of decadal variability exhibits an increased frequency of higher waves in the present decade compared to the past. Linear trend analysis show significant upswing in spatially averaged ERA-20C mean wave period, whereas the noticed variations are marginal in the ERA-Interim data. A separate trend analysis for the wind-seas, swell wave heights and period from ERA-20C decipher the fact that distant swells governs the local wind-wave climatology over the head Bay region, and over time the swell activity have increased in this region.

Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

PubMed

Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Kameda, Hiroyuki; Tamura, Masahiro; Mihara, Hanako; Kaku, Kohei

2016-09-01

Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

What is the impact of different VLBI analysis setups of the tropospheric delay on precipitable water vapor trends?

NASA Astrophysics Data System (ADS)

Balidakis, Kyriakos; Nilsson, Tobias; Heinkelmann, Robert; Glaser, Susanne; Zus, Florian; Deng, Zhiguo; Schuh, Harald

2017-04-01

The quality of the parameters estimated by global navigation satellite systems (GNSS) and very long baseline interferometry (VLBI) are distorted by erroneous meteorological observations applied to model the propagation delay in the electrically neutral atmosphere. For early VLBI sessions with poor geometry, unsuitable constraints imposed on the a priori tropospheric gradients is a source of additional hassle of VLBI analysis. Therefore, climate change indicators deduced from the geodetic analysis, such as the long-term precipitable water vapor (PWV) trends, are strongly affected. In this contribution we investigate the impact of different modeling and parameterization of the propagation delay in the troposphere on the estimates of long-term PWV trends from geodetic VLBI analysis results. We address the influence of the meteorological data source, and of the a priori non-hydrostatic delays and gradients employed in the VLBI processing, on the estimated PWV trends. In particular, we assess the effect of employing temperature and pressure from (i) homogenized in situ observations, (ii) the model levels of the ERA Interim reanalysis numerical weather model and (iii) our own blind model in the style of GPT2w with enhanced parameterization, calculated using the latter data set. Furthermore, we utilize non-hydrostatic delays and gradients estimated from (i) a GNSS reprocessing at GeoForschungsZentrum Potsdam, rigorously considering tropospheric ties, and (ii)) direct ray-tracing through ERA Interim, as additional observations. To evaluate the above, the least-squares module of the VieVS@GFZ VLBI software was appropriately modified. Additionally, we study the noise characteristics of the non-hydrostatic delays and gradients estimated from our VLBI and GNSS analyses as well as from ray-tracing. We have modified the Theil-Sen estimator appropriately to robustly deduce PWV trends from VLBI, GNSS, ray-tracing and direct numerical integration in ERA Interim. We disseminate all our solutions in the latest Tropo-SINEX format.

PROJECT W-551 INTERIM PRETREATMENT SYSTEM PRECONCEPTUAL CANDIDATE TECHNOLOGY DESCRIPTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

MAY TH

The Office of River Protection (ORP) has authorized a study to recommend and select options for interim pretreatment of tank waste and support Waste Treatment Plant (WTP) low activity waste (LAW) operations prior to startup of all the WTP facilities. The Interim Pretreatment System (IPS) is to be a moderately sized system which separates entrained solids and 137Cs from tank waste for an interim time period while WTP high level waste vitrification and pretreatment facilities are completed. This study's objective is to prepare pre-conceptual technology descriptions that expand the technical detail for selected solid and cesium separation technologies. This revisionmore » includes information on additional feed tanks.« less

Sensitivity Analysis for Multidisciplinary Systems (SAMS)

DTIC Science & Technology

2016-12-01

support both mode-based structural representations and time-dependent, nonlinear finite element structural dynamics. This interim report describes...Adaptation, & Sensitivity Toolkit • Elasticity, heat transfer, & compressible flow • Adjoint solver for sensitivity analysis • High-order finite elements ...PROGRAM ELEMENT NUMBER 62201F 6. AUTHOR(S) Richard D. Snyder 5d. PROJECT NUMBER 2401 5e. TASK NUMBER N/A 5f. WORK UNIT NUMBER Q1FS 7

Surface Acoustic Wave Transducer Study.

DTIC Science & Technology

1978-05-01

B. Network Analysis 48 C. Experimental Results 53 D. Conc lusions 56 VI. Analysis of SAW Propagation in Layered Structures . . . 56 A. Introduction...unLdtrect1ona~ transducer and the associated matching networks . The capacity weighted transducer consists of a layered structure in which the lower...CAPACITIVELY WEIGHTED TRANSDUCERS A. Introduction The capacitive tap weight network transducer (CNN) has been pre- .5 sented in the interim as an

The utility of Bayesian predictive probabilities for interim monitoring of clinical trials

PubMed Central

Connor, Jason T.; Ayers, Gregory D; Alvarez, JoAnn

2014-01-01

Background Bayesian predictive probabilities can be used for interim monitoring of clinical trials to estimate the probability of observing a statistically significant treatment effect if the trial were to continue to its predefined maximum sample size. Purpose We explore settings in which Bayesian predictive probabilities are advantageous for interim monitoring compared to Bayesian posterior probabilities, p-values, conditional power, or group sequential methods. Results For interim analyses that address prediction hypotheses, such as futility monitoring and efficacy monitoring with lagged outcomes, only predictive probabilities properly account for the amount of data remaining to be observed in a clinical trial and have the flexibility to incorporate additional information via auxiliary variables. Limitations Computational burdens limit the feasibility of predictive probabilities in many clinical trial settings. The specification of prior distributions brings additional challenges for regulatory approval. Conclusions The use of Bayesian predictive probabilities enables the choice of logical interim stopping rules that closely align with the clinical decision making process. PMID:24872363

INTERIM -- Starlink Software Environment

NASA Astrophysics Data System (ADS)

Pearce, Dave; Pavelin, Cliff; Lawden, M. D.

Early versions of this paper were based on a number of other papers produced at a very early stage of the Starlink project. They contained a description of a specific implementation of a subroutine library, speculations on the desirable attributes of a software environment, and future development plans. They reflected the experimental nature of the Starlink software environment at that time. Since then, the situation has changed. The implemented subroutine library, INTERIM_DIR:INTERIM.OLB, is now a well established and widely used piece of software. A completely new Starlink software environment (ADAM) has been developed and distributed. Thus the library released in 1980 as `STARLINK' and now called `INTERIM' has reached the end of its development cycle and is now frozen in its current state, apart from bug corrections. This paper has, therefore, been completely rewritten and restructured to reflect the new situation. Its aim is to describe the facilities of the INTERIM subroutine library as clearly and concisely as possible. It avoids speculation, discussion of design decisions, and announcements of future plans.

17 CFR 402.2a - Appendix A-Calculation of market risk haircut for purposes of § 402.2(g)(2).

Code of Federal Regulations, 2014 CFR

2014-04-01

... larger in absolute value of the two residual position interim haircuts being netted, and (ii) zero, in... category of the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in... the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in the...

17 CFR 402.2a - Appendix A-Calculation of market risk haircut for purposes of § 402.2(g)(2).

Code of Federal Regulations, 2011 CFR

2011-04-01

... larger in absolute value of the two residual position interim haircuts being netted, and (ii) zero, in... category of the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in... the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in the...

17 CFR 402.2a - Appendix A-Calculation of market risk haircut for purposes of § 402.2(g)(2).

Code of Federal Regulations, 2012 CFR

2012-04-01

... larger in absolute value of the two residual position interim haircuts being netted, and (ii) zero, in... category of the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in... the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in the...

17 CFR 402.2a - Appendix A-Calculation of market risk haircut for purposes of § 402.2(g)(2).

Code of Federal Regulations, 2010 CFR

2010-04-01

... larger in absolute value of the two residual position interim haircuts being netted, and (ii) zero, in... category of the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in... the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in the...

17 CFR 402.2a - Appendix A-Calculation of market risk haircut for purposes of § 402.2(g)(2).

Code of Federal Regulations, 2013 CFR

2013-04-01

... larger in absolute value of the two residual position interim haircuts being netted, and (ii) zero, in... category of the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in... the larger (in absolute value) of the two interim haircuts that were netted, and (2) a zero in the...

Interim Report by Asia International Grid Connection Study Group

NASA Astrophysics Data System (ADS)

Omatsu, Ryo

2018-01-01

The Asia International Grid Connection Study Group Interim Report examines the feasibility of developing an international grid connection in Japan. The Group has investigated different cases of grid connections in Europe and conducted research on electricity markets in Northeast Asia, and identifies the barriers and challenges for developing an international grid network including Japan. This presentation introduces basic contents of the interim report by the Study Group.

Commentary: Interim leadership of academic departments at U.S. medical schools.

PubMed

Grigsby, R Kevin; Aber, Robert C; Quillen, David A

2009-10-01

Medical schools and teaching hospitals are experiencing more frequent turnover of department chairs. Loss of a department chair creates instability in the department and may have a negative effect on the organization at large. Interim leadership of academic departments is common, and interim chairs are expected to immediately demonstrate skills and leadership abilities. However, little is known about how persons are prepared to assume the interim chair role. Newer competencies for effective leadership include an understanding of the business of medicine, interpersonal and communication skills, the ability to deal with conflict and solve adaptive challenges, and the ability to build and work on teams. Medical schools and teaching hospitals need assistance to meet the unique training and support needs of persons serving as interim leaders. For example, the Association of American Medical Colleges and individual chair societies can develop programs to allow current chairs to reflect on their present positions and plan for the future. Formal leadership training, mentorship opportunities, and conscientious succession planning are good first steps in preparing to meet the needs of academic departments during transitions in leadership. Also, interim leadership experience may be useful as a means for "opening the door" to underrepresented persons, including women, and increasing the diversity of the leadership team.

Reinforcement of a PMMA resin for interim fixed prostheses with silica nanoparticles.

PubMed

Topouzi, Marianthi; Kontonasaki, Eleana; Bikiaris, Dimitrios; Papadopoulou, Lambrini; Paraskevopoulos, Konstantinos M; Koidis, Petros

2017-05-01

Fractures in long span provisional/interim restorations are a common complication. Adequate fracture toughness is necessary to resist occlusal forces and crack propagation, so these restorations should be constructed with materials of improved mechanical properties. The aim of this study was to investigate the possible reinforcement of neat silica nanoparticles and trietoxyvinylsilane-modified silica nanoparticles in a PMMA resin for fixed interim restorations. Composite PMMA-Silica nanoparticles powders were mixed with PMMA liquid and compact bar shaped specimens were fabricated according to the British standard BS EN ISO 127337:2005. The single-edge notched method was used to evaluate fracture toughness (three-point bending test), while the dynamic thermomechanical properties (Storage Modulus, Loss Modulus, tanδ) of a series of nanocomposites with different amounts of nanoparticles (0.25%, 0.50%, 0.75%, 1% w.t.) were evaluated. Statistical analysis was performed and the statistically significant level was set to p<0.05. The fracture toughness of all experimental composites was remarkably higher compared to control. There was a tendency to decrease of fracture toughness, by increasing the concentration of the filler. No statistically significant differences were detected among the modified/unmodified silica nanoparticles. Dynamic mechanical properties were also affected. By increasing the silica nanoparticles content an increase in Storage Modulus was recorded, while Glass Transition Temperature was shifted at higher temperatures. Under the limitations of this in-vitro study, it can be suggested that both neat silica nanoparticles and trietoxyvinylsilane-modified silica nanoparticles, especially at low concentrations, may enhance the overall performance of fixed interim prostheses, as can effectively increase the fracture toughness, the elastic modulus and the Glass Transition Temperature of PMMA resins used in fixed provisional restorations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spring snow albedo feedback over northern Eurasia: Comparing in situ measurements with reanalysis products

NASA Astrophysics Data System (ADS)

Wegmann, Martin; Dutra, Emanuel; Jacobi, Hans-Werner; Zolina, Olga

2018-06-01

This study uses daily observations and modern reanalyses in order to evaluate reanalysis products over northern Eurasia regarding the spring snow albedo feedback (SAF) during the period from 2000 to 2013. We used the state-of-the-art reanalyses from ERA-Interim/Land and the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2) as well as an experimental set-up of ERA-Interim/Land with prescribed short grass as land cover to enhance the comparability with the station data while underlining the caveats of comparing in situ observations with gridded data. Snow depth statistics derived from daily station data are well reproduced in all three reanalyses. However day-to-day albedo variability is notably higher at the stations than for any reanalysis product. The ERA-Interim grass set-up shows improved performance when representing albedo variability and generates comparable estimates for the snow albedo in spring. We find that modern reanalyses show a physically consistent representation of SAF, with realistic spatial patterns and area-averaged sensitivity estimates. However, station-based SAF values are significantly higher than in the reanalyses, which is mostly driven by the stronger contrast between snow and snow-free albedo. Switching to grass-only vegetation in ERA-Interim/Land increases the SAF values up to the level of station-based estimates. We found no significant trend in the examined 14-year time series of SAF, but interannual changes of about 0.5 % K-1 in both station-based and reanalysis estimates were derived. This interannual variability is primarily dominated by the variability in the snowmelt sensitivity, which is correctly captured in reanalysis products. Although modern reanalyses perform well for snow variables, efforts should be made to improve the representation of dynamic albedo changes.

Figure 1 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

Cancer.gov

A screenshot of the IGV user interface at the chromosome view. IGV user interface showing five data types (copy number, methylation, gene expression, and loss of heterozygosity; mutations are overlaid with black boxes) from approximately 80 glioblastoma multiforme samples. Adapted from Figure S1; Robinson et al. 2011

Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

ClinicalTrials.gov

2016-02-18

Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon

2011-09-01

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors beforemore » definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.« less

Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme.

PubMed

Nam, L; Coll, C; Erthal, L C S; de la Torre, C; Serrano, D; Martínez-Máñez, R; Santos-Martínez, M J; Ruiz-Hernández, E

2018-05-11

Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood⁻brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.

Altered Expression of Polycomb Group Genes in Glioblastoma Multiforme

PubMed Central

Li, Gang; Warden, Charles; Zou, Zhaoxia; Neman, Josh; Krueger, Joseph S.; Jain, Alisha; Jandial, Rahul; Chen, Mike

2013-01-01

The Polycomb group (PcG) proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM). By systematically interrogating The Cancer Genome Atlas (TCGA), we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy. PMID:24260522

Altered expression of polycomb group genes in glioblastoma multiforme.

PubMed

Li, Gang; Warden, Charles; Zou, Zhaoxia; Neman, Josh; Krueger, Joseph S; Jain, Alisha; Jandial, Rahul; Chen, Mike

2013-01-01

The Polycomb group (PcG) proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM). By systematically interrogating The Cancer Genome Atlas (TCGA), we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.

HSP27 knockdown produces synergistic induction of apoptosis by HSP90 and kinase inhibitors in glioblastoma multiforme.

PubMed

Belkacemi, Louiza; Hebb, Matthew O

2014-09-01

The heat-shock proteins HSP27 and HSP90 perpetuate the malignant nature of glioblastoma multiforme (GBM) and offer promise as targets for novel cancer therapeutics. The present study sought to define synergistic antitumor benefits of concurrent HSP27-knockdown and the HSP90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) or, comparatively, the non-selective kinase inhibitor, staurosporine, in GBM cells. Dose-response relations were determined for 17-AAG and staurosporine in three GBM cell lines. HSP27-targeted siRNA was administered alone or in combination with subtherapeutic concentrations of each drug and cells were evaluated for viability, proliferation and apoptosis. Adjuvant HSP27 knockdown with 17-AAG or staurosporine produced marked and synergistic decrease in GBM cell viability and proliferation, with robust elevation of apoptotic fractions and caspase-3 activation. HSP27 knockdown confers potent chemosensitization of GBM cells. These novel data support the development of HSP-targeting strategies and, specifically, anti-HSP27 agents for the treatment of GBM. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme

PubMed Central

Günzle, Jessica; Osterberg, Nadja; Saavedra, Joseph E; Weyerbrock, Astrid

2016-01-01

The nitric oxide (NO) donor JS-K is specifically activated by glutathione S-transferases (GSTs) in GST-overexpressing cells. We have shown the induction of cell death in glioblastoma multiforme (GBM) cells at high JS-K doses but the mechanism remains unclear. The aim of this study was to determine whether NO-induced cell death is triggered by induction of apoptotic or necrotic pathways. For the first time, we demonstrate that NO induces cell death via mitotic catastrophe (MC) with non-apoptotic mechanisms in GBM cells. Moreover, the level of morphological changes indicating MC correlates with increased necrosis. Therefore, we conclude that MC is the main mechanism by which GBM cells undergo cell death after treatment with JS-K associated with necrosis rather than apoptosis. In addition, we show that PARP1 is not an exclusive marker for late apoptosis but is also involved in MC. Activating an alternative way of cell death can be useful for the multimodal cancer therapy of GBM known for its strong anti-apoptotic mechanisms and drug resistance. PMID:27584787

Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme.

PubMed

Günzle, Jessica; Osterberg, Nadja; Saavedra, Joseph E; Weyerbrock, Astrid

2016-09-01

The nitric oxide (NO) donor JS-K is specifically activated by glutathione S-transferases (GSTs) in GST-overexpressing cells. We have shown the induction of cell death in glioblastoma multiforme (GBM) cells at high JS-K doses but the mechanism remains unclear. The aim of this study was to determine whether NO-induced cell death is triggered by induction of apoptotic or necrotic pathways. For the first time, we demonstrate that NO induces cell death via mitotic catastrophe (MC) with non-apoptotic mechanisms in GBM cells. Moreover, the level of morphological changes indicating MC correlates with increased necrosis. Therefore, we conclude that MC is the main mechanism by which GBM cells undergo cell death after treatment with JS-K associated with necrosis rather than apoptosis. In addition, we show that PARP1 is not an exclusive marker for late apoptosis but is also involved in MC. Activating an alternative way of cell death can be useful for the multimodal cancer therapy of GBM known for its strong anti-apoptotic mechanisms and drug resistance.

The PEP-3-KLH (CDX-110) vaccine in glioblastoma multiforme patients

PubMed Central

Heimberger, Amy B.; Sampson, John H

2009-01-01

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed on GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received the vaccines targeting EGFRvIII had an unexpectedly long survival time. Further therapeutic strategies and potential pitfalls using this approach are discussed. PMID:19591631

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

PubMed

Shea, Amanda; Harish, Varsha; Afzal, Zainab; Chijioke, Juliet; Kedir, Habib; Dusmatova, Shahnoza; Roy, Arpita; Ramalinga, Malathi; Harris, Brent; Blancato, Jan; Verma, Mukesh; Kumar, Deepak

2016-08-01

Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Canine parvovirus-2b-associated erythema multiforme in a litter of English Setter dogs.

PubMed

Woldemeskel, Moges; Liggett, Alan; Ilha, Marcia; Saliki, Jeremiah T; Johnson, Leslie P

2011-05-01

Erythema multiforme (EM) was diagnosed in a litter of English Setter puppies. The puppies developed erythematous cutaneous lesions at the age of 2 weeks. Microscopically, there was individual keratinocyte apoptosis associated with lymphocyte exocytosis in all layers of the epidermis. Intranuclear viral inclusions were seen in multiple tissues and organs. Tissues from the tongue, lymph node, spleen, skin, and small intestine were positive for Canine parvovirus-2 (CPV-2) and negative for Canine distemper virus (CDV) and Canid herpesvirus 1 by fluorescent antibody test. Negative-staining electron microscopy detected parvovirus particles in the intestinal contents. The skin and small intestine were positive for CPV-2b and negative for CDV by polymerase chain reaction. The mucocutaneous junctions and small intestines stained positive for CPV by immunohistochemistry. The present report documents CPV-2b-associated EM in a litter of English Setters and substantiates the single previous report associating EM with CPV-2. The finding suggests that CPV should be considered as a possible cause of EM in dogs. © 2011 The Author(s)

Where Does the Irrigation Water Go? An Estimate of the Contribution of Irrigation to Precipitation Using MERRA

NASA Technical Reports Server (NTRS)

Wei, Jiangfeng; Dirmeyer, Paul A.; Wisser, Dominik; Bosilovich, Michael G.; Mocko, David M.

2013-01-01

Irrigation is an important human activity that may impact local and regional climate, but current climate model simulations and data assimilation systems generally do not explicitly include it. The European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim) shows more irrigation signal in surface evapotranspiration (ET) than the Modern-Era Retrospective Analysis for Research and Applications (MERRA) because ERA-Interim adjusts soil moisture according to the observed surface temperature and humidity while MERRA has no explicit consideration of irrigation at the surface. But, when compared with the results from a hydrological model with detailed considerations of agriculture, the ET from both reanalyses show large deficiencies in capturing the impact of irrigation. Here, a back-trajectory method is used to estimate the contribution of irrigation to precipitation over local and surrounding regions, using MERRA with observation-based corrections and added irrigation-caused ET increase from the hydrological model. Results show substantial contributions of irrigation to precipitation over heavily irrigated regions in Asia, but the precipitation increase is much less than the ET increase over most areas, indicating that irrigation could lead to water deficits over these regions. For the same increase in ET, precipitation increases are larger over wetter areas where convection is more easily triggered, but the percentage increase in precipitation is similar for different areas. There are substantial regional differences in the patterns of irrigation impact, but, for all the studied regions, the highest percentage contribution to precipitation is over local land.