Refractory Research Group - U.S. DOE, Albany Research Center [Institution Profile

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

Bennett, James P.

2004-09-01

The refractory research group at the Albany Research Center (ARC) has a long history of conducting materials research within the U.S. Bureau of Mines, and more recently, within the U.S. Dept. of Energy. When under the U.S. Bureau of Mines, research was driven by national needs to develop substitute materials and to conserve raw materials. This mission was accomplished by improving refractory material properties and/or by recycling refractories using critical and strategic materials. Currently, as a U.S. Dept of Energy Fossil Energy field site, research is driven primarily by the need to assist DOE in meeting its vision to developmore » economically and environmentally viable technologies for the production of electricity from fossil fuels. Research at ARC impacts this vision by: • Providing information on the performance characteristics of materials being specified for the current generation of power systems; • Developing cost-effective, high performance materials for inclusion in the next generation of fossil power systems; and • Solving environmental emission and waste problems related to fossil energy systems. A brief history of past refractory research within the U.S. Bureau of Mines, the current refractory research at ARC, and the equipment and capabilities used to conduct refractory research at ARC will be discussed.« less

Radiotherapy With or Without Surgery for Patients With Idiopathic Sclerosing Orbital Inflammation Refractory or Intolerant to Steroid Therapy

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

Lee, Jong Hoon; Kim, Yeon-Sil, E-mail: yeonkim7@catholic.ac.kr; Yang, Suk Woo

Purpose: To evaluate the outcomes of patients with idiopathic sclerosing orbital inflammation (ISOI) treated with radiotherapy with or without surgery. Methods and Materials: We retrospectively reviewed 22 patients with histopathologically confirmed ISOI who had been refractory or intolerant to steroid therapy and treated with radiation with or without surgery. The radiation dose ranged from 20 to 40 Gy (median, 20 Gy) at 2 Gy per fraction. Presenting signs and treatment outcomes were assessed. Results: Proptosis was the most common sign at presentation, seen in 19 (86.3%) patients, followed by restriction of extraocular movements in 10 (45.4%) patients. Response to radiotherapymore » was complete in 15 (68.1%) patients, partial in 3 (13.6%) patients, and none in 4 (18.2%) patients. At the median follow-up of 34 months, 14 (63.6%) patients had progression-free state of symptoms and signs, with the progression-free duration ranging from 3 to 75 months (median, 41.5 months), whereas 8 (36.4%) patients had recurrent or persistent disease although they had received radiotherapy. Of the 14 progression-free patients, 6 underwent a bimodality treatment of debulking surgery of ocular disease and radiotherapy. They had had no recurrent disease. Cataract was the most common late complications, and 2 patients experienced a Grade 3 cataract. Conclusion: Our study suggests that for patients with ISOI who are refractory or intolerant to steroid therapy, 20 Gy of radiotherapy appears to be effective for the control of disease with acceptable complications, especially when it is combined with surgery.« less

Refractory Materials for Flame Deflector Protection System Corrosion Control: Flame Deflector Protection System Life Cycle Cost Analysis Report

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Coffman, Brekke E.; Kolody, Mark R.; Curran, Jerome P.; Trejo, David; Reinschmidt, Ken; Kim, Hyung-Jin

2009-01-01

A 20-year life cycle cost analysis was performed to compare the operational life cycle cost, processing/turnaround timelines, and operations manpower inspection/repair/refurbishment requirements for corrosion protection of the Kennedy Space Center launch pad flame deflector associated with the existing cast-in-place materials and a newer advanced refractory ceramic material. The analysis compared the estimated costs of(1) continuing to use of the current refractory material without any changes; (2) completely reconstructing the flame trench using the current refractory material; and (3) completely reconstructing the flame trench with a new high-performance refractory material. Cost estimates were based on an analysis of the amount of damage that occurs after each launch and an estimate of the average repair cost. Alternative 3 was found to save $32M compared to alternative 1 and $17M compared to alternative 2 over a 20-year life cycle.

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

PubMed Central

Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

2010-01-01

Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

Neutral Na in comets tails: a chemical story

NASA Astrophysics Data System (ADS)

Ellinger, Y.; Pauzat, F.; Mousis, O.; Guilbert-Lepoutre, A.; Leblanc, F.; Ali-Dib, M.; Doronin, M.; Zicler, E.; Doressoundiram, A.

2015-10-01

The origin of the neutral sodium comet tail discovered in comet Hale-Bopp in 1997 is still a matter of discussion. Here we propose a scenario which is based on chemical grounds. The starting point is the chemical trapping of the Na+ ion in the refractory material during the condensation phase of the protosolar nebula, followed by its incorporation in the building blocks of the comets parent bodies. In the next step, the Na+ ions are washed out of the refractory material by the water formed by the melting of the ice due to the heat released in the radioactive decay of short period elements. When the water freezes again, the Na+ ion looses its positive charge to evolve progressively toward a neutral atom when approaching the surface of the ice. As shown by high-level numerical simulations based on first principle periodic density functional theory (DFT) to describe the solid structure of the ice, it is a neutral Na that is ejected with the sublimation of the ice top layer.

Improved refractory performance through partnership

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

Linck, F.E.; Peters, D.

1995-12-31

From the early designs and construction of Circulating Fluidized Bed (CFB) boilers, many improvements have been made based upon observations of performance. Included in these improvements have been the refractory linings. The early refractory linings were subjected to extreme fluctuations in temperatures as the units experienced up and down conditions. As the designs were improved refractory failures were mostly due to the operating conditions and other mechanical stresses rather than continual shutdowns and startups. More recent problems observed with refractory linings are localized areas of high erosion, corrosion and cracking which result in hot spots and eventual shutdowns for repair.more » Today the objective of refractory suppliers and installers is to strive towards planned shutdowns rather than emergency shutdowns. This can be accomplished through partnerships between operations, material suppliers and installers. In essence, the concept is a cooperative effort between these groups to solve the variety of refractory problems in order to achieve longer refractory lining performance and less chance for emergency shutdowns. The reliability of the refractory lining is dependent on the successful combination of the material selected, proper design and the installation of the refractory material. Where these three elements combine, the lining has the best chance of performing its intended purpose.« less

Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

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

Tseng, Yolanda D., E-mail: ydt2@uw.edu; Chen, Yu-Hui; Catalano, Paul J.

Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treatedmore » with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter TTLR, suggesting that radiation dose escalation, addition of radiosensitizers, or a combination of both may be indicated in these patients.« less

High temperature lined conduits, elbows and tees

DOEpatents

De Feo, Angelo; Drewniany, Edward

1982-01-01

A high temperature lined conduit comprising, a liner, a flexible insulating refractory blanket around and in contact with the liner, a pipe member around the blanket and spaced therefrom, and castable rigid refractory material between the pipe member and the blanket. Anchors are connected to the inside diameter of the pipe and extend into the castable material. The liner includes male and female slip joint ends for permitting thermal expansion of the liner with respect to the castable material and the pipe member. Elbows and tees of the lined conduit comprise an elbow liner wrapped with insulating refractory blanket material around which is disposed a spaced elbow pipe member with castable refractory material between the blanket material and the elbow pipe member. A reinforcing band is connected to the elbow liner at an intermediate location thereon from which extend a plurality of hollow tubes or pins which extend into the castable material to anchor the lined elbow and permit thermal expansion. A method of fabricating the high temperature lined conduit, elbows and tees is also disclosed which utilizes a polyethylene layer over the refractory blanket after it has been compressed to maintain the refractory blanket in a compressed condition until the castable material is in place. Hot gases are then directed through the interior of the liner for evaporating the polyethylene and setting the castable material which permits the compressed blanket to come into close contact with the castable material.

Composition and process for making an insulating refractory material

DOEpatents

Pearson, A.; Swansiger, T.G.

1998-04-28

A composition and process are disclosed for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4--2.6 g/cm{sup 3} with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness.

Nano-composite materials

DOEpatents

Lee, Se-Hee; Tracy, C. Edwin; Pitts, J. Roland

2010-05-25

Nano-composite materials are disclosed. An exemplary method of producing a nano-composite material may comprise co-sputtering a transition metal and a refractory metal in a reactive atmosphere. The method may also comprise co-depositing a transition metal and a refractory metal composite structure on a substrate. The method may further comprise thermally annealing the deposited transition metal and refractory metal composite structure in a reactive atmosphere.

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

2011-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

2010-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Testing Requirements for Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W,; Montgomery, Eliza M.

2012-01-01

Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1 G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

Synthesis of refractory materials

DOEpatents

Holt, Joseph B.

1984-01-01

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

Synthesis of refractory materials

DOEpatents

Holt, J.B.

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

Refractory Materials for Flame Deflector Protection System Corrosion Control: Similar Industries and/or Launch Facilities Survey

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Coffman, Brekke E.; Sampson, Jeffrey W.; Kolody, Mark R.; Curran, Jerome P.; Perusich, Stephen A.; Trejo, David; Whitten, Mary C.;

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.

PubMed

Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P; Sweiss, Nadera J

2016-03-01

Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.

Doxorubicin-Loaded 70–150 μm Microspheres for Liver-Dominant Metastatic Breast Cancer: Results and Outcomes of a Pilot Study

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

Lin, Yen-Ting, E-mail: ymerically@gmail.com; Médioni, Jacques, E-mail: jacques.medioni@aphp.fr; Amouyal, Grégory, E-mail: gregory.amouyal@aphp.fr

PurposePatients with breast cancer liver metastasis have a poor prognosis. Local therapy for liver metastasis increases survival. The purpose of this pilot prospective study was to evaluate the efficacy and safety of doxorubicin drug-eluting beads chemoembolization for liver-dominant breast cancer metastasis (LdBM) refractory to chemotherapy.Materials and MethodsAll patients with LdBM refractory to of two or more lines of systemic chemotherapy were screened. Two chemoembolizations at 1-month intervals were scheduled for each patient. Tumor responses were evaluated by MRI every 3 months until progression or death. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.02)more » 1 month after each chemoembolization. All patients were free from systemic treatment until progression. Patients with hormone-positive receptors and/or HER-positive disease status continued their targeted therapy.ResultsOut of 23 patients enrolled (mean age: 57.5 ± 11.5 years), 17 completed two chemoembolizations and six underwent only one because of severe adverse events. At 3-month follow-up, the disease control rate was 83 %. The median progression-free survival from the first chemoembolization was 8 months, and the median overall survival was 17 months. Nineteen patients remained free from any systemic chemotherapy for a mean of 209 ± 92 days until progression. Eight grade 3 (asthenia n = 3, anemia n = 2, thrombocythemia n = 2, liver toxicity n = 1) (Rev 1 Comment 1) occurred after the first procedure. No patient died directly due to the procedure.ConclusionWhile chemoembolization with doxorubicin eluding beads for refractory LdBM leads to an 83 % disease control rate, it also causes severe side effects that need to be adequately managed.« less

Composition and process for making an insulating refractory material

DOEpatents

Pearson, Alan; Swansiger, Thomas G.

1998-04-28

A composition and process for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4-2.6 g/cm.sup.3 with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness, good abrasion resistance and crush strength.

Inorganic composites for space applications

NASA Technical Reports Server (NTRS)

Malmendier, J. W.

1984-01-01

The development of inorganic composite materials for space applications is reviewed. The composites do not contain any organic materials, and therefore, are not subject to degradation by ultraviolet radiation, volatilization of constituents, or embrittlement at low temperatures. The composites consist of glass, glass/ceramics or ceramic matrices, reinforced by refractory whiskers or fibers. Such composites have the low thermal expansion, refractories, chemical stability and other desirable properties usually associated with the matrix materials. The composites also have a degree of toughness which is extraordinary for refractory inorganic materials.

Electrochemical cell with powdered electrically insulative material as a separator

DOEpatents

Mathers, James P.; Olszanski, Theodore W.; Boquist, Carl W.

1978-01-01

A secondary electrochemical cell includes electrodes separated by a layer of electrically insulative powder. The powder includes refractory materials selected from the oxides and nitrides of metals and metaloids. The powdered refractory material, blended with electrolyte particles, can be compacted in layers with electrode materials to form an integral electrode structure or separately assembled into the cell. The assembled cell is heated to operating temperature leaving porous layers of electrically insulative, refractory particles, containing molten electrolyte between the electrodes.

Commercial off-the-Shelf (COTS) Refractory Material Evaluation

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Kolody, Mark R.; Curran, Jerome P.; Back, Teddy; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Perusich, Stephen; Bucherl, Cori

2009-01-01

Fondu Fyre (FF) is currently the only refractory material qualified for use in the flame trench at KSC's Shuttle Launch Pads 39A and 39B. However, the material is not used as it was qualified and has undergone increasingly frequent and severe degradation due to the launch blasts. This degradation is costly as well as dangerous for launch infrastructure, crew and vehicle. FF is applied at the pad via the gunnite process, where wetted refractory material is sprayed onto a steel grid mounted on a support structure. The water content in this process can be manually adjusted by operators, causing distinct visual and physical discrepancies among repair areas. Since the application process is unlikely to change for new refractory materials, it is important to understand the effects of water content on commercial off-the-shelf (COTS) refractory materials. The purpose of this study was to evaluate the performance of the FF with respect to various water contents as well as heat treatments, to simulate aging and exposure to the blast. Initial results indicated that different water contents and heat treatments result in distinct differences in crushing strength, apparent porosity and bulk density. However, water content became an insignificant factor in both crush strength and porosity when FF was cured to at least 1500 deg. Additionally, inspection of the material's surface microstructure by scanning electron microscopy indicated distinguishable characteristics for different heat treatment levels. Results from this study will help guide future studies on the development and identification of new refractory materials.

Method of making a composite refractory material

DOEpatents

Morrow, Marvin S.; Holcombe, Cressie E.

1995-01-01

A composite refractory material is prepared by combining boron carbide with furan resin to form a mixture containing about 8 wt. % furan resin. The mixture is formed into a pellet which is placed into a grit pack comprising an oxide of an element such as yttrium to form a sinterable body. The sinterable body is sintered under vacuum with microwave energy at a temperature no greater than 2000.degree. C. to form a composite refractory material.

Method of making a composite refractory material

DOEpatents

Morrow, M.S.; Holcombe, C.E.

1995-09-26

A composite refractory material is prepared by combining boron carbide with furan resin to form a mixture containing about 8 wt. % furan resin. The mixture is formed into a pellet which is placed into a grit pack comprising an oxide of an element such as yttrium to form a sinterable body. The sinterable body is sintered under vacuum with microwave energy at a temperature no greater than 2000 C to form a composite refractory material.

Simulation of meso-damage of refractory based on cohesion model and molecular dynamics method

NASA Astrophysics Data System (ADS)

Zhao, Jiuling; Shang, Hehao; Zhu, Zhaojun; Zhang, Guoxing; Duan, Leiguang; Sun, Xinya

2018-06-01

In order to describe the meso-damage of the refractories more accurately, and to study of the relationship between the mesostructured of the refractories and the macro-mechanics, this paper takes the magnesia-carbon refractories as the research object and uses the molecular dynamics method to instead the traditional sequential algorithm to establish the meso-particles filling model including small and large particles. Finally, the finite element software-ABAQUS is used to conducts numerical simulation on the meso-damage evolution process of refractory materials. From the results, the process of initiation and propagation of microscopic interface cracks can be observed intuitively, and the macroscopic stress-strain curve of the refractory material is obtained. The results show that the combination of molecular dynamics modeling and the use of Python in the interface to insert the cohesive element numerical simulation, obtaining of more accurate interface parameters through parameter inversion, can be more accurate to observe the interface of the meso-damage evolution process and effective to consider the effect of the mesostructured of the refractory material on its macroscopic mechanical properties.

Microwave Measurement of Refractory Materials at High-Temperature

NASA Astrophysics Data System (ADS)

Kharkovsky, S.; Zoughi, R.; Smith, J.; Davis, B.; Limmer, R.

2009-03-01

Knowledge of the electrical behavior of refractory materials may enable the development and optimization of microwave nondestructive techniques to detect and evaluate changes in their physical properties while the materials are in service. This paper presents the results of a limited and preliminary investigation in which two refractory materials (dense chrome and dense zircon) were subjected to increasing temperature in a furnace and in which a frequency-modulated continuous-wave radar operating in the frequency range of 8-18 GHz radar was used to evaluate their attenuation properties.

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-26

B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

Corrosion resistance of ceramic refractories to simulated waste glasses at high temperature

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

Xing, S.B.; Lin, Y.; Mohr, R.K.

1996-08-01

In many vitrification processes, refractory materials are used to contain the waste glass melt. The corrosive nature of the high-temperature melt consumes the waste feed materials but also limits refractory life. As vitrification is applied to more diverse waste streams, and particularly in higher-temperature applications, increasingly severe demands are placed on the refractory materials. A variety of potential refractory materials including Fused-cast AZS, Monofrax K3, Monofrax E, and the Corhart refractories ER1195, ER2161, C1215, C1215Z, Rechrome, and T1186, were subjected to corrosion testing at 1,450 C using the ASTM C-621 procedure. A series of simulated waste glasses was used whichmore » included F, Cl, S, Cu, Zn, Pb; these minor components were found to cause significant, and in some cases drastic, increases in corrosion rates. The corrosion tests were conducted over a range of time intervals extending to 144 hrs in order to investigate the kinetics of the corrosion processes. The change of the concentrations of constituents in the glass was monitored by compositional analysis of glass samples and correlated to the observed extent of corrosion; typically, components of the material under test increase with time while key minor components, such as Co and Pb, decrease. The rate of corrosion of high-zirconia refractories was slowed considerably by adding zirconia to the waste glass composition; this has the added benefit of improving the aqueous leach resistance of the waste form that is produced.« less

Gasification Slag and the Mechanisms by Which Phosphorous Additions Reduce Slag Wear and Corrosion in High Cr2O3 Refractories

NASA Astrophysics Data System (ADS)

Bennett, James; Nakano, Anna; Nakano, Jinichiro; Thomas, Hugh

Gasification is a high-temperature/high-pressure process that converts carbonaceous materials such as coal and/or petcoke into CO and H2, feedstock materials used in power generation and chemical production. Gasification is considered an important technology because of its high process efficiency and the ability to capture environmental pollutants such as CO2, SO3 and Hg. Ash impurities in the carbon feedstock materials melt and coalesce during gasification (1325-1575 °C), becoming slag that attaches to and flows down the gasifier sidewall, corroding and eroding the high Cr2O3 refractory liner used to protect the gasification chamber. Phosphate additions to high Cr2O3 refractory have been found to alter slag/refractory interactions and dramatically reduce refractory wear by the following mechanisms: a) spinel formation, b) slag chemistry changes, c) two phase liquid formation, and d) oxidation state changes. The mechanisms and how they work together to impact material wear/corrosion will be discussed.

Compatibility of refractory materials for nuclear reactor poison control systems

NASA Technical Reports Server (NTRS)

Sinclair, J. H.

1974-01-01

Metal-clad poison rods have been considered for the control system of an advanced space power reactor concept studied at the NASA Lewis Research Center. Such control rods may be required to operate at temperatures of about 140O C. Selected poison materials (including boron carbide and the diborides of zirconium, hafnium, and tantalum) were subjected to 1000-hour screening tests in contact with candidate refractory metal cladding materials (including tungsten and alloys of tantalum, niobium, and molybdenum) to assess the compatibility of these materials combinations at the temperatures of interest. Zirconium and hafnium diborides were compatible with refractory metals at 1400 C, but boron carbide and tantalum diboride reacted with the refractory metals at this temperature. Zirconium diboride also showed promise as a reaction barrier between boron carbide and tungsten.

DEVELOPMENT OF DIES FOR EXTRUSION OF COMPLEX SHAPES OF STEEL AND REFRACTORY ALLOYS. Interim Technical Documentary Progress Report to Aeronautical Systems Division for the Period September 16,1962 through December 31, 1962

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

Hunt, J.G.; Jenkins, R.G.; White, A.M.

1963-03-01

A number of ceramics, metallic compounds, and ceramic-metal composites were successfully hot pressed into the shape of die inserts. Steels were extruded through several of these for the purpose of evaluating the materials or to study methods of supporting the die inserts. Refractory metal inserts were also used in similar tests. Hot pressed inserts consisting of 80 vo1% Al/sub 2/O/ sub 3/--10 vol% W and 80 vol% ThO/sub 2/--10 vol% W cracked but did not erode. Sintered molybdenum inserts flowed excessively, whereas sintered tungsten inserts flowed to a lesser degree. A hard die casing with a slight shrink fit appearsmore » to be the most satisfactory method of support. (auth)« less

Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer.

PubMed

Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

2012-06-01

Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported. Copyright © 2012 Elsevier Inc. All rights reserved.

Compatibility Studies of Various Refractory Materials in Contact with Molten Silicon

NASA Technical Reports Server (NTRS)

Odonnell, T.; Leipold, M. H.; Hagan, M.

1978-01-01

The production of low cost, efficient solar cells for terrestrial electric power generation involves the manipulation of molten silicon with a present need for noncontaminating, high temperature refractories to be used as containment vessels, ribbon-production dies, and dip-coated substrates. Studies were conducted on the wetting behavior and chemical/physical interactions between molten silicon and various refractory materials.

Niobium-Matrix-Composite High-Temperature Turbine Blades

NASA Technical Reports Server (NTRS)

Kaplan, Richard B.; Tuffias, Robert H.; La Ferla, Raffaele; Heng, Sangvavann; Harding, John T.

1995-01-01

High-temperture composite-material turbine blades comprising mainly niobium matrices reinforced with refractory-material fibers being developed. Of refractory fibrous materials investigated, FP-AL(2)0(3), tungsten, and polymer-based SiC fibers most promising. Blade of this type hollow and formed in nearly net shape by wrapping mesh of reinforcing refractory fibers around molybdenum mandrel, then using thermal-gradient chemical-vapor infiltration (CVI) to fill interstices with niobium. CVI process controllable and repeatable, and kinetics of both deposition and infiltration well understood.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

PubMed Central

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

The Use Of Phosphates To Reduce Slag Penetration In Cr203-Based Refractories

DOEpatents

Kwong, Kyei-Sing; Dogan, Cynthia P.; Bennett, James P.; Chinn, Richard E.; Petty, Arthur V.

2004-11-09

A high-chromium refractory material that provides improved resistance to coal slag penetration is presented. The refractory mixture comprises a blend of chromium oxide, aluminum oxide and phosphates. The refractory mixture may be blended with an aggregate and cured. In addition a phosphorous oxide may be blended with chromium oxide and aluminum oxide and additionally an aggregate. The refractory mixture reduces the rate of coal slag penetration into the surface of the cured refractory.

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax.

PubMed

Anderson, Mary Ann; Tam, Constantine; Lew, Thomas E; Juneja, Surender; Juneja, Manu; Westerman, David; Wall, Meaghan; Lade, Stephen; Gorelik, Alexandra; Huang, David C S; Seymour, John F; Roberts, Andrew W

2017-06-22

The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials. Investigations at progression included positron emission tomography scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and 8 with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) ( P = .003). Among patients who received the recommended phase 2 dose of venetoclax or higher (≥400 mg/d), fludarabine refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 [95% confidence interval 1.7-28.5]; P = .002 and 6.6 [1.5-29.8]; P = .005, respectively), whereas del(17p) and/or TP53 mutation were not ( P = .75). Median postprogression survival was 13 (<1-49.9) months. Bruton tyrosine kinase inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine refractory or who have complex cytogenetics should have occult RT excluded before initiating venetoclax therapy. © 2017 by The American Society of Hematology.

Advanced refractory-metal and process technology for the fabrication of x-ray masks

NASA Astrophysics Data System (ADS)

Brooks, Cameron J.; Racette, Kenneth C.; Lercel, Michael J.; Powers, Lynn A.; Benoit, Douglas E.

1999-06-01

This paper provides an in-depth report of the advanced materials and process technology being developed for x-ray mask manufacturing at IBM. Masks using diamond membranes as replacement for silicon carbide are currently being fabricated. Alternate tantalum-based absorbers, such as tantalum boron, which offer improved etch resolution and critical dimension control, as well as higher x-ray absorption, are also being investigated. In addition to the absorber studies, the development of conductive chromium- based hard-mask films to replace the current silicon oxynitride layer is being explored. The progress of this advanced-materials work, which includes significant enhancements to x-ray mask image-placement performance, will be outlined.

Corrosion assessment of refractory materials for high temperature waste vitrification

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

Marra, J.C.; Congdon, J.W.; Kielpinski, A.L.

1995-11-01

A variety of vitrification technologies are being evaluated to immobilize radioactive and hazardous wastes following years of nuclear materials production throughout the Department of Energy (DOE) complex. The compositions and physical forms of these wastes are diverse ranging from inorganic sludges to organic liquids to heterogeneous debris. Melt and off-gas products can be very corrosive at the high temperatures required to melt many of these waste streams. Ensuring material durability is required to develop viable treatment processes. Corrosion testing of materials in some of the anticipated severe environments is an important aspect of the materials identification and selection process. Corrosionmore » coupon tests on typical materials used in Joule heated melters were completed using glass compositions with high salt contents. The presence of chloride in the melts caused the most severe attack. In the metal alloys, oxidation was the predominant corrosion mechanism, while in the tested refractory material enhanced dissolution of the refractory into the glass was observed. Corrosion testing of numerous different refractory materials was performed in a plasma vitrification system using a surrogate heterogeneous debris waste. Extensive corrosion was observed in all tested materials.« less

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Dietary prevention of hormone refractory prostate cancer in Lobund-Wistar rats: a review of studies in a relevant animal model.

PubMed

Pollard, Morris; Suckow, Mark A

2006-12-01

Lobund-Wistar (LW) rats, which have high testosterone levels, are predisposed to develop hormone-refractory prostate cancer (HRPC) spontaneously and by methylnitrosourea (MNU) induction, and the development of HRPC progresses through 2 stages. This paper reviews several studies in which LW rats were placed on soy-containing diets and were evaluated for development of either spontaneous or MNU-induced prostate cancer. The premalignant, testosterone-dependent stage is inhibited by testosterone deprivation. In the absence of testosterone deprivation, tumorigenesis progresses spontaneously to the testosterone-independent refractory stage. In LW rats: moderate caloric restriction prevented development of spontaneous prostate cancer; dietary 4-hydroxyphenylretinamide prevented MNU-induced prostate cancer; and dietary supplementation with soy protein isolate with high isoflavones prevented spontaneous and induced tumors and led to moderate reduction of serum testosterone. In rats 12 mo of age and younger, changing from the control diet to the soy+isoflavone diet significantly prevented progression of spontaneous tumors to the refractory stage of disease. Tumors that developed spontaneously and after MNU induction showed similar developmental stages and morphology, but MNU-induced tumors had shorter latency periods before development. The accumulated data indicate that soy-based diets are effective in the prevention of prostate cancer.

Emissivity Results on High Temperature Coatings for Refractory Composite Materials

NASA Technical Reports Server (NTRS)

Ohlhorst, Craig W.; Vaughn, Wallace L.; Daryabeigi, Kamran; Lewis, Ronald K.; Rodriguez, Alvaro C.; Milhoan, James D.; Koenig, John R.

2007-01-01

The directional emissivity of various refractory composite materials considered for application for reentry and hypersonic vehicles was investigated. The directional emissivity was measured at elevated temperatures of up to 3400 F using a directional spectral radiometric technique during arc-jet test runs. A laboratory-based relative total radiance method was also used to measure total normal emissivity of some of the refractory composite materials. The data from the two techniques are compared. The paper will also compare the historical database of Reinforced Carbon-Carbon emissivity measurements with emissivity values generated recently on the material using the two techniques described in the paper.

Practical aspects of the use of phosphate binding materials in refractory mixtures, mortars and putties

NASA Technical Reports Server (NTRS)

Soltysik, B.; Pawelek, A.; Witkowska, E.

1983-01-01

Phosphate binders, particularly acidic phosphates of Al and Cr, are used for binding Al silicate refractories used for lining of burners, SiC refractories, and refractory mortars. The binders have apparent d. 2.13-2.18 g/cu cm, porosity 21.4-23.8%, compressive strength 223 71 kg/ sq cm, total shrinkage 0.2-0.8%, and refractoriness 1240 deg.

Comparison of Refractory Performance in Black Liquor Gasifiers and a Smelt Test System

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

Peascoe, RA

2001-09-25

Prior laboratory corrosion studies along with experience at the black liquor gasifier in New Bern, North Carolina, clearly demonstrate that serious material problems exist with the gasifier's refractory lining. Mullite-based and alumina-based refractories used at the New Bern facility suffered significant degradation even though they reportedly performed adequately in smaller scale systems. Oak Ridge National Laboratory's involvement in the failure analysis, and the initial exploration of suitable replacement materials, led to the realization that a simple and reliable, complementary method for refractory screening was needed. The development of a laboratory test system and its suitability for simulating the environment ofmore » black liquor gasifiers was undertaken. Identification and characterization of corrosion products were used to evaluate the test system as a rapid screening tool for refractory performance and as a predictor of refractory lifetime. Results from the test systems and pl ants were qualitatively similar.« less

Forming Refractory Insulation On Copper Wire

NASA Technical Reports Server (NTRS)

Setlock, J.; Roberts, G.

1995-01-01

Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

Attachment system for silica tiles. [thermal protection for space shuttle orbiter

NASA Technical Reports Server (NTRS)

Dotts, R. L.; Holt, J. W. (Inventor)

1982-01-01

An improved method for markedly increasing the bond strength between a rigid, porous refractory material and non-rigid substrate by densifying the face of the rigid material opposing the substrate is discussed. Densification is accomplished by wetting the refractory material and then impregnating it with a composite slurry having a particle size to fill voids of the porous material.

40 CFR 61.161 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... material charger systems, heat exchangers, melter cooling system, exhaust system, refractory brick work... the bottom, sidewalls, or roof of the melting vessel; replacement of refractory work in the heat exchanger; and replacement of refractory portions of the glass conditioning and distribution system...

40 CFR 61.161 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... material charger systems, heat exchangers, melter cooling system, exhaust system, refractory brick work... the bottom, sidewalls, or roof of the melting vessel; replacement of refractory work in the heat exchanger; and replacement of refractory portions of the glass conditioning and distribution system...

40 CFR 61.161 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... material charger systems, heat exchangers, melter cooling system, exhaust system, refractory brick work... the bottom, sidewalls, or roof of the melting vessel; replacement of refractory work in the heat exchanger; and replacement of refractory portions of the glass conditioning and distribution system...

40 CFR 61.161 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... material charger systems, heat exchangers, melter cooling system, exhaust system, refractory brick work... the bottom, sidewalls, or roof of the melting vessel; replacement of refractory work in the heat exchanger; and replacement of refractory portions of the glass conditioning and distribution system...

Laboratory Investigations of the Complex Refractory Organic Material Produced from Irradiation of Pluto Ice Analogs

NASA Technical Reports Server (NTRS)

Materese, Christopher K.; Cruikshank, Dale P.; Sanford, Scott A.; Imanaka, Hiroshi

2014-01-01

Much of Pluto's surface consists of N2 ice with smaller amounts of CH4 and CO ices. Despite the low temperature (approximately 45K), chemistry can be driven in the surface ices by radiation processing such as cosmic ray bombardment. When cosmic rays strike the surface, much of their energy is dispersed in the form of secondary electrons, which in turn drive much of the resulting chemical reactions. Laboratory experiments designed to simulate the conditions on these icy bodies may provide insight into this chemistry. Significant progress has been made in the laboratory toward understanding the smaller, simple compounds produced in the solid phase by radiation processing of (N2, CH4, CO) ices (Bohn et al. 1994; Moore & Hudson 2003; Hodyss et al. 2011; Kim and Kaiser 2012). Recently Materese et al. (2014) used a variety of techniques to better characterize the refractory materials produced from the UV photo-irradiation of N2:CH4:CO ices. However, because Pluto's atmosphere is optically thick to Lyman-alpha UV radiation it is important to re-examine the results using an alternate radiation source. Our latest work has consisted of the analysis of refractory materials produced from the electron bombardment of low temperature N2(-), CH4(-), and CO(-)containing ices (100:1:1). The ice mixture was chosen to be analogous to the known surface ices on Pluto and the radiation source was chosen to mimic the secondary electrons produced by cosmic rays bombardment. The residues were studied using multiple chemical techniques including, infrared (IR) spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). The organic residues produced in these experiments can be seen as an analog for the refractory component of the surface of Pluto, and are compared with the residues previously obtained from UV photo-irradiation. UV and near- IR spectroscopy of the surfaces of Pluto and Charon during the encounter with NASA's New Horizons spacecraft in 2015, will give the first close-up measurements of ices and their photoproducts. Laboratory measurements and experiments will provide a better context for the data returned by the spacecraft.

Method of preparing a powdered, electrically insulative separator for use in an electrochemical cell

DOEpatents

Cooper, Tom O.; Miller, William E.

1978-01-01

A secondary electrochemical cell includes electrodes separated by a layer of electrically insulative powder. The powder includes refractory materials selected from the oxides and nitrides of metals and metaloids. The powdered refractory material, blended with electrolyte particles, is compacted as layers onto an electrode to form an integral electrode structure and assembled into the cell. The assembled cell is heated to its operating temperature leaving porous layers of electrically insulative, refractory particles, containing molten electrolyte between the electrodes.

Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study.

PubMed

Burstein, Harold J; Demetri, George D; Mueller, Elisabetta; Sarraf, Pasha; Spiegelman, Bruce M; Winer, Eric P

2003-06-01

To evaluate the therapeutic effects of the peroxisome proliferator-activated receptor (PPAR) gamma activating ligand, troglitazone, in patients with refractory metastatic breast cancer. Patients with advanced breast cancer refractory to at least one chemotherapy regimen (ER negative tumors) or two hormonal regimens (ER positive tumors) were treated with troglitazone at 800 mg p.o. QD until disease progression, to determine the percentage of patients free of progression at 6 months. Tumor response, toxicity, and changes in serum tumor markers (CEA, CA27.29) that might reflect alteration in tumor differentiation, were also examined. Twenty-two patients were enrolled before suspension of protocol accrual and treatment when troglitazone was withdrawn from commercial availability following FDA warnings on hepatic toxicity. No objective responses (CR or PR) were observed; only three patients had SD at 8 weeks. Patients came off study for PD (16), DLT (1), FDA withdrawal (2), or other (3) reasons. No patients took troglitazone for more than 20 weeks; all had experienced disease progression or began other systemic therapy within 6 months. All patients with elevated serum tumor markers (CEA and CA27.29) at baseline had rising tumor markers within 8 weeks. While clinical trials among different patient populations might uncover subtle effects on tumor differentiation, PPARgamma activation by troglitazone has little apparent clinical value among patients with treatment-refractory metastatic breast cancer.

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

PubMed Central

Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

2015-01-01

Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment. PMID:25962114

Emission spectrometric arcing procedure with minimal effect of chemical form of sample. [performed on refractory metal matrix composites

NASA Technical Reports Server (NTRS)

Gordon, W. A.

1975-01-01

Matrix effects related to the chemical form of analyzed materials were studied. An arc in argon was used which was buffered with silver chloride. The effect of chemical form was minimal for a variety of metals, oxides, and carbides representing the most refractory compounds and thermally stable metal-containing molecules. Only four of the most refractory materials known showed significant emission depressions due to incomplete volatilization in the arc system. These results are discussed in terms of vapor pressures of the solid materials placed on the anodes and dissociation reactions of the molecules in the gaseous environment.

Progress in NMR Studies of Liquid Ceramic Materials

NASA Astrophysics Data System (ADS)

Marzke, Robert F.; Piwowarczyk, Jeremy; Boucher, Susan; Wolf, George H.

2003-10-01

The availability of molten, levitated samples of Al-containing ceramics at temperatures of 2,000^oC and higher permits a broad range of important materials to be investigated by the powerful techniques of NMR.footnote Coutures, J-P., Massiot, D., Bessada, C., Echegut, P., Rifflet, J-C. & Taulelle F., Etude par RMN 27Al daluminates liquides dans le domaine 1600-2100 ^oC. C.R. Acad. Sci. Paris, 1990, 310, 1041. Standard measurements of chemical shift as a function of composition yield information concerning the bonding of Al and the structure of liquid phases, for both novel and well-studied refractory materials. Studies of incoherent motions in a sample, such as Al diffusion or time-dependent convective currents, may also be performed when magnetic field gradients are incorporated into the experimental NMR probe. Recent advances are reviewed, in several research areas.

Burner systems

DOEpatents

Doherty, Brian J.

1984-07-10

A burner system particularly useful for downhole deployment includes a tubular combustion chamber unit housed within a tubular coolant jacket assembly. The combustion chamber unit includes a monolithic tube of refractory material whose inner surface defines the combustion zone. A metal reinforcing sleeve surrounds and extends the length of the refractory tube. The inner surface of the coolant jacket assembly and outer surface of the combustion chamber unit are dimensioned so that those surfaces are close to one another in standby condition so that the combustion chamber unit has limited freedom to expand with that expansion being stabilized by the coolant jacket assembly so that compression forces in the refractory tube do not exceed about one-half the safe compressive stress of the material; and the materials of the combustion chamber unit are selected to establish thermal gradient parameters across the combustion chamber unit to maintain the refractory tube in compression during combustion system start up and cool down sequences.

[Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer: a possibility for secondary hormonal ablation?].

PubMed

Schilling, D; Küfer, R; Kruck, S; Stenzl, A; Kuczyk, M A; Merseburger, A S

2008-10-01

Almost all patients with hormone-refractory prostate cancer under primary androgen deprivation therapy will develop progression, frequently initially marked by an asymptomatic increase of prostate-specific antigen (PSA). Recent data showed that taxane-based chemotherapy offers significant survival benefit to patients with advanced prostate cancer; however, the toxic side effects frequently exert a significant negative impact on the quality of life. At the androgen-independent stage of the cancer, before becoming hormone refractory, progression might still be delayed by secondary manipulation of either androgen or confounding receptors and their signaling pathways. Secondary hormonal manipulations traditionally included antiandrogen withdrawal, second-line antiandrogens, direct adrenal androgen inhibitors, estrogens, and progestins.We discuss the mode of action and application of somatostatin analogs as an emerging secondary hormonal treatment concept in patients with advanced prostate cancer on the basis of the current literature.

Background research in support of the new grant proposal: Research consortium for X-ray topography on line X-19 at NSLS

NASA Astrophysics Data System (ADS)

Bilello, J. C.

1983-11-01

The status of the construction and installation of components of the synchrotron topography station is reported as well as progress in the development of hardware for interfacing and software for interactively controlling the 13 motors which automate the facility. Research focuses on the problem of X-ray optics and on techniques for applying topography to materials science. There is colaboration with other researchers in studying the nature of brittle fracture of refractory metals and in interpreting contact in the vicinity of crack tips.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

PubMed

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. Janssen Research & Development, LLC. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Dust and silica exposure on metallurgical furnace maintenance using refractory materials].

PubMed

Garattini, S; Barbieri, P G; Bottone, F; Brunelli, E; Carminati, F; Chiari, R; Sarnico, M

2012-01-01

In the metallurgical industries the silica risk has long been known, particularly for the refractoryes maintenance workers. The maintenance of furnaces, ladles and tundisches refractory linings, on the current organization of production, is provided by companies under contract. The information available about the characterization of risk for this group of workers are at present inadequate. The study investigates the exposure to dust, also containing free crystalline silica (SLC), through the analysis of samples of commercial products used in the reconstruction of refractory linings of furnaces, ladles and tundisches, materials from the demolition of refractory articles and dust from work areas. It also presents the results of an environmental investigation conducted during the demolition and reconstruction of the refractory in three steel mills. The Authors, by the numerous inspections and the systematic survey of working conditions, have formulated a SLC risk profile and some proposals for prevention.

Materials Chemistry Issues in the Development of a Single-Crystal Solar/Thermal Refractive Secondary Concentrator

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.; Biering, Robert C.

2005-01-01

A translucent crystal concentrates and transmits energy to a heat exchanger, which in turn heats a propellant gas, working gas of a dynamic power system, or a thermopile. Materials are the limiting issue in such a system. Central is the durability of the crystal, which must maintain the required chemical, physical/optical, and mechanical properties as it is heated and cooled. This report summarizes available data to date on the materials issues with this system. We focus on the current leading candidate materials, which are sapphire (Al2O3) for higher temperatures and silica (SiO2) for lower temperatures. We use data from thermochemical calculations; laboratory coupon tests with silica and sapphire; and system tests with sapphire. The required chemical properties include low-vapor pressure and interfacial stability with supporting structural materials. Optical properties such as transmittance and index of refraction must be maintained. Thermomechanical stability is a major challenge for a large, single-crystal ceramic and has been discussed in another report. In addition to the crystal, other materials in the proposed system include refractory metals (Nb, Ta, Mo, W, and Re), carbon (C), and high-temperature ceramic insulation. The major issue here is low levels of oxygen, which lead to volatile refractory metal oxides and rapid consumption of the refractory metal. Interfacial reactions between the ceramic crystal and refractory metal are also discussed. Finally, high-temperature ceramic insulating materials are also likely to be used in this system. Outgassing is a major issue for these materials. The products of outgassing are typically reactive with the refractory metals and must be minimized.

Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

PubMed

Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

2015-04-01

Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma.

PubMed

Sasse, Stephanie; Rothe, Achim; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Kreher, Stephan; Jäger, Ulrich; Bangard, Christopher; Kuhnert, Georg; Böll, Boris; von Tresckow, Bastian; Engert, Andreas

2013-10-01

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT (n = 4) or allogeneic SCT (n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL.

Refractory electrodes for joule heating and methods of using same

DOEpatents

Lamar, David A.; Chapman, Chris C.; Elliott, Michael L.

1998-01-01

A certain group of electrically conductive refractory materials presently known for use in high temperature applications as throat constructions, melter sidewalls, forehearth, stacks, port sills, hot face lining for slagging coal gasifiers, slag runners, and linings for nuclear waste encapsulation furnaces may be used as electrodes permitting joule heating at temperatures in excess of 1200 C. in excess of about 4400 hours even in the presence of transition group element(s). More specifically, the invention is an electrode for melting earthen materials, wherein the electrode is made from an electrically conductive refractory material, specifically at least one metal oxide wherein the metal is selected from the group consisting of chrome, ruthenium, rhodium, tin and combinations thereof.

Effects of Temperature, Oxygen Partial Pressure, and Materials Selection on Slag Infiltration into Porous Refractories for Entrained-Flow Gasifiers

NASA Astrophysics Data System (ADS)

Kaneko, Tetsuya Kenneth

The penetration rate of molten mineral contents (slag) from spent carbonaceous feedstock into porous ceramic-oxide refractory linings is a critical parameter in determining the lifecycle of integrated gasification combined cycle energy production plants. Refractory linings that withstand longer operation without interruption are desirable because they can mitigate consumable and maintenance costs. Although refractory degradation has been extensively studied for many other high-temperature industrial processes, this work focuses on the mechanisms that are unique to entrained-flow gasification systems. The use of unique feedstock mixtures, temperatures from 1450 °C to 1600 °C, and oxygen partial pressures from 10-7 atm to 10-9 atm pose engineering challenges in designing an optimal refractory material. Experimentation, characterization, and modeling show that gasifier slag infiltration into porous refractory is determined by interactions between the slag and the refractory that either form a physical barrier that impedes fluid flow or induce an increased fluid viscosity that decelerates the velocity of the fluid body. The viscosity of the slag is modified by the thermal profile of the refractory along the penetration direction as well as reactions between the slag and refractory that alter the chemistry, and thereby the thermo-physical properties of the fluid. Infiltration experiments reveal that the temperature gradient inherently present along the refractory lining limits penetration. A refractory in near-isothermal conditions demonstrates deeper slag penetration as compared to one that experiences a steeper thermal profile. The decrease in the local temperatures of the slag as it travels deeper into the refractory increases the viscosity of the fluid, which in turn slows the infiltration velocity of fluid body into the pores of the refractory microstructure. With feedstock mixtures that exhibit high iron-oxide concentrations, a transition-metal-oxide, the oxygen partial pressure of the operating atmosphere regulates the penetration of slag into refractory. The viscosity of the slag, which dictates its penetration rate, is influenced by the oxidation state of the Fe cation. Slag penetrations are shallower in oxidizing conditions than they are in reducing conditions because the iron-oxide from the slag solutions into the corundum-structured refractory and the slag is depleted of iron-oxide, increasing the viscosity of slags. Equally, the chemistries of both the refractory and slag materials dictate the course of penetration. Cr2O3-Al2O3 refractory limits mixed feedstock slag penetration through formation of a chromium spinel layer that functions as a physical obstacle against fluid flow. Al2O 3-SiO2 refractory limits eastern coal feedstock slag penetration as a result of refractory dissolution of SiO2, which increases the viscosity of slags. A physical model, which considers unidirectional fluid flow of slag through each pore of the porous microstructure of the refractory, sufficiently approximates the penetration depth of the slag into the refractory. Agreement between experiments and the physical model demonstrates that the slag is driven into the refractory by capillary pressure. Since the viscosity of the slag continuously changes as the slag travels through the inherent temperature gradient of the refractory lining, the model incorporates dynamic viscosities that are dependent on both temperature and composition to project depths that are unique to the experimental parameters. The significantly different length scales of the radial and penetration directions of the pores allows for the application of a lubrication approximation onto the momentum equation. This process produces an analytical solution that effectively envelopes the variable viscosity into a single term.

Preliminary experience with a new device for delayed sternal closure strategy in cardiac surgery.

PubMed

Santini, Francesco; Onorati, Francesco; Telesca, Mariassunta; Faggian, Giuseppe; Mazzucco, Alessandro

2012-06-01

Open chest management with delayed sternal closure (DSC) is a valuable strategy in the management of patients with postcardiotomy hemodynamic instability or severe coagulopathy. The conventional extemporized material available for off-label sternal stenting however may limit its efficacy. We evaluated outcomes of patients with refractory severe postcardiotomy cardiogenic shock (SPCCS) treated with DSC using a novel temporary sternal spreader (NTSS) which allows myocardial recovery by progressive controlled approximation of the sternal edges. Seven patients (4 male, mean age 66.5 ± 5 years) with refractory SPCCS showing acute hemodynamic instability at sternal closure, were implanted with the NTSS, consisting of stainless-steel branches linked to 2 diverging plates of polyether-ether ketone, whose progressive opening/closing mechanism can be controlled from outside the chest with a rotating steel wire. The sternal wound was closed by an elastic membrane to achieve a sterile field. Swan-Ganz monitoring was employed, and clinical outcomes evaluated. The device was successfully implanted in all patients without device-related complications or failures. Progressive approximation of sternal edges, titrated on cardiac index values, was successfully completed allowing subsequent uneventful sternal closure in all. Mean time from SPCCS to sternal closure was 70 ± 21 hours. No patient developed infective complications or late hemodynamic instability after device removal and sternal closure. One patient (14%) died of multiorgan failure on postoperative day 9. Despite the limited number of patients enrolled, the NTSS proved safe and effective in allowing complete myocardial recovery after SPCCS, avoiding hemodynamic instability related to abrupt sternal closure, with no occurrence of infective complications.

Theoretical and Experimental Investigations on the Mechanism of Carbothermal Reduction of Zirconia (Preprint)

DTIC Science & Technology

2012-08-01

Properties. Abyss Books, Washington, D.C., 2002. 2. G. Montel, A. Lebugle and H. Pastor. "Manufacture of Materials Containing Refractory Borides ...and ZrO2," International Journal of Refractory Metals and Hard Materials, 17, 235-43 (1999). 10. A.W. Weimer, Carbide, nitride and boride

Refractory Materials for Flame Deflector Protection

NASA Technical Reports Server (NTRS)

Calle, Luz M.; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Curran, Jerome P.; Kolody, Mark R.; Peruisich, Stephen A.

2010-01-01

Fondu Fyre (FF) is currently the only refractory material qualified for use in the flame trench at KSC's Shuttle Launch Pads 39A and 3913. However, the material is not used as it was qualified and has undergone increasingly frequent and severe degradation due to the launch blasts. This degradation is costly as well as dangerous for launch infrastructure, crew and vehicle. The launch environment at KSC is unique. The refractory material is subject to the normal seacoast environment, is completely saturated with water before launch, and is subjected to vibrations and aggressive heat/blast conditions during launch. This report presents results comparing two alternate materials, Ultra-Tek FS gun mix and Kruzite GR Plus, with Fondu Fyre. The materials were subjected to bulk density, porosity, compression strength, modulus of rupture and thermal shock tests. In addition, test specimens were exposed to conditions meant to simulate the launch environment at KSC to help better understand how the materials will perform once installed.

Laboratory studies of refractory metal oxide smokes

NASA Technical Reports Server (NTRS)

Nuth, Joseph A.; Nelson, R. N.; Donn, Bertram

1989-01-01

Studies of the properties of refractory metal oxide smokes condensed from a gas containing various combinations of SiH4, Fe(CO)5, Al(CH3)3, TiCl4, O2 and N2O in a hydrogen carrier stream at 500 K greater than T greater than 1500 K were performed. Ultraviolet, visible and infrared spectra of pure, amorphous SiO(x), FeO(x), AlO(x) and TiO(x) smokes are discussed, as well as the spectra of various co-condensed amorphous oxides, such as FE(x)SiO(y) or Fe(x)AlO(y). Preliminary studies of the changes induced in the infrared spectra of iron-containing oxide smokes by vacuum thermal annealing suggest that such materials become increasingly opaque in the near infrared with increased processing: hydration may have the opposite effect. More work on the processing of these materials is required to confirm such a trend: this work is currently in progress. Preliminary studies of the ultraviolet spectra of amorphous Si2O3 and MgSiO(x) smokes revealed no interesting features in the region from 200 to 300 nm. Studies of the ultraviolet spectra of both amorphous, hydrated and annealed SiO(x), TiO(x), AlO(x) and FeO(x) smokes are currently in progress. Finally, data on the oxygen isotopic composition of the smokes produced in the experiments are presented, which indicate that the oxygen becomes isotopically fractionated during grain condensation. Oxygen in the grains is as much as 3 percent per amu lighter than the oxygen in the original gas stream. The authors are currently conducting experiments to understand the mechanism by which fractionation occurs.

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

PubMed

Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

2018-05-02

The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Control for monitoring thickness of high temperature refractory

DOEpatents

Caines, M.J.

1982-11-23

This invention teaches an improved monitoring device for detecting the changes in thickness of high-temperature refractory, the device consists of a probe having at least two electrically conductive generally parallel elements separated by a dielectric material. The probe is implanted or embedded directly in the refractory and is elongated to extend in line with the refractory thickness to be measured. Electrical inputs to the conductive elements provide that either or both the electrical conductance or capacitance can be found, so that charges over lapsed time periods can be compared in order to detect changes in the thickness of the refractory.

Mineral resource of the month: kyanite

USGS Publications Warehouse

Potter, Michael J.

2007-01-01

Kyanite and related minerals are used in making refractories, which are materials that can withstand high-temperature environments, generally in excess of 1,100 degrees Celsius. Refractories form an inner lining to furnaces, kilns and other containers with which molten metals and glass come into contact. Fifty to 70 percent of global refractory consumption is related to the steel industry.

Refractory electrodes for joule heating and methods of using same

DOEpatents

Lamar, D.A.; Chapman, C.C.; Elliott, M.L.

1998-05-12

A certain group of electrically conductive refractory materials presently known for use in high temperature applications as throat constructions, melter sidewalls, forehearth, stacks, port sills, hot face lining for slagging coal gasifiers, slag runners, and linings for nuclear waste encapsulation furnaces may be used as electrodes permitting joule heating at temperatures in excess of 1,200 C in excess of about 4400 hours even in the presence of transition group element(s). More specifically, the invention is an electrode for melting earthen materials, wherein the electrode is made from an electrically conductive refractory material, specifically at least one metal oxide wherein the metal is selected from the group consisting of chrome, ruthenium, rhodium, tin and combinations thereof. 2 figs.

Annual Research Progress Report, Fiscal Year 1979,

DTIC Science & Technology

1979-10-01

Infusion on 58 Hemoglobin Oxygen Carrying Patterns in Man. (0) (PR) C-6-78 Minoxidil as an Anti-Hypertensive in Patients 59 Refractory to Available...aspirin. Ann. Int. Med. 89:1006, 1978. Rubin, E.N., Walker, B.K., Ersler, A.J., et al. Euthyroid aplasia complicating collagen vascular disease...Texas 78234 CLINICAL INVESTIGATION SERVICE INVESTIGATION PROJECT RESUME TITLE: Minoxidil as an Anti-Hypertensive in Patients Refractory to Available

Annual Research Progress Report, Fiscal Year 1979,

DTIC Science & Technology

1979-10-01

Chemoimmunotherapy of Carcinoma of the Large 27 Bowel. (T) 77-8 Minoxidil as an Antihypertensive in Patients 29 Refractory to Available Medications. (T) 77-11...INVESTIGATION SERVICE INVESTIGATION PROJECT RESUME TITLE: Minoxidil as an Antihypertensive in Patients Refractory to Available Medications. WORK UNIT...NO: 77-8 (Satellite Protocol of FAMC) PRINCIPAL INVESTIGATOR: James H. Wilkin, MD, LTC, MD OBJECTIVES To test the hypothesis that minoxidil is an

The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation.

PubMed

Batman, Cosar; Ozdamar, Yasemin

2010-01-01

To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. Copyright 2010, SLACK Incorporated.

ICE CHEMISTRY ON OUTER SOLAR SYSTEM BODIES: ELECTRON RADIOLYSIS OF N{sub 2}-, CH{sub 4}-, AND CO-CONTAINING ICES

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

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.

Radiation processing of the surface ices of outer Solar System bodies may be an important process for the production of complex chemical species. The refractory materials resulting from radiation processing of known ices are thought to impart to them a red or brown color, as perceived in the visible spectral region. In this work, we analyzed the refractory materials produced from the 1.2-keV electron bombardment of low-temperature N{sub 2}-, CH{sub 4}-, and CO-containing ices (100:1:1), which simulates the radiation from the secondary electrons produced by cosmic ray bombardment of the surface ices of Pluto. Despite starting with extremely simple icesmore » dominated by N{sub 2}, electron irradiation processing results in the production of refractory material with complex oxygen- and nitrogen-bearing organic molecules. These refractory materials were studied at room temperature using multiple analytical techniques including Fourier-transform infrared spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). Infrared spectra of the refractory material suggest the presence of alcohols, carboxylic acids, ketones, aldehydes, amines, and nitriles. XANES spectra of the material indicate the presence of carboxyl groups, amides, urea, and nitriles, and are thus consistent with the IR data. Atomic abundance ratios for the bulk composition of these residues from XANES analysis show that the organic residues are extremely N-rich, having ratios of N/C ∼ 0.9 and O/C ∼ 0.2. Finally, GC-MS data reveal that the residues contain urea as well as numerous carboxylic acids, some of which are of interest for prebiotic and biological chemistries.« less

Ice Chemistry on Outer Solar System Bodies: Electron Radiolysis of N2-, CH4-, and CO-Containing Ices

NASA Astrophysics Data System (ADS)

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.; Imanaka, Hiroshi; Nuevo, Michel

2015-10-01

Radiation processing of the surface ices of outer Solar System bodies may be an important process for the production of complex chemical species. The refractory materials resulting from radiation processing of known ices are thought to impart to them a red or brown color, as perceived in the visible spectral region. In this work, we analyzed the refractory materials produced from the 1.2-keV electron bombardment of low-temperature N2-, CH4-, and CO-containing ices (100:1:1), which simulates the radiation from the secondary electrons produced by cosmic ray bombardment of the surface ices of Pluto. Despite starting with extremely simple ices dominated by N2, electron irradiation processing results in the production of refractory material with complex oxygen- and nitrogen-bearing organic molecules. These refractory materials were studied at room temperature using multiple analytical techniques including Fourier-transform infrared spectroscopy, X-ray absorption near-edge structure (XANES) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). Infrared spectra of the refractory material suggest the presence of alcohols, carboxylic acids, ketones, aldehydes, amines, and nitriles. XANES spectra of the material indicate the presence of carboxyl groups, amides, urea, and nitriles, and are thus consistent with the IR data. Atomic abundance ratios for the bulk composition of these residues from XANES analysis show that the organic residues are extremely N-rich, having ratios of N/C ∼ 0.9 and O/C ∼ 0.2. Finally, GC-MS data reveal that the residues contain urea as well as numerous carboxylic acids, some of which are of interest for prebiotic and biological chemistries.

Non-CI refractory lithophile abundances in bulk planetary materials

NASA Astrophysics Data System (ADS)

Dauphas, N.

2015-12-01

Refractory inclusions in meteorites show evidence for fractionation of refractory lithophile elements relative to one another. For bulk planetary materials, it is most often assumed that refractory lithophile elements (e.g., Ca, Al, Ti, REEs) are in proportions similar to CI carbonaceous chondrites, which is taken to be a proxy for solar composition. A diagnostic feature of REE patterns in refractory inclusions in meteorites is the presence of thulium anomalies, arising from the fact that this heavy REE is more volatile than the highly refractory HREEs surrounding it (Tm/Tm* is defined relative to either Er-Yb or Er-Lu). Tm anomalies thus represent an excellent diagnostic tool to test the assumption that refractory lithophile elements have uniform relative abundances at a bulk planetary scale. Prior to this work, high precision Tm measurements were lacking because it is mono-isotopic and as such is not amenable to high-precision single spike measurements. We have developed a multi-collector REE abundance measurement technique to measure all REEs at high precision, including the mono-isotopic ones. This technique was used to revise the abundance of CI and PAAS REE abundances (Pourmand et al. 2012) and the CI composition agrees well with an independent study (Barrat et al. 2012). The same technique was applied to measure REE patterns in 41 chondrites as well as terrestrial rocks (Dauphas and Pourmand, 2015). Our results reveal the presence of Tm anomalies of about -4.5 % in terrestrial rocks, enstatite and ordinary chondrites, relative to carbonaceous chondrites including CIs. This demonstrates that the assumption that refractory lithophile elements are in constant proportions among planetary bodies is unwarranted. It also shows that carbonaceous chondrites cannot be a major constituent of the Earth. The presence of Tm anomalies in meteorites and terrestrial rocks suggests that either (i) the material in the inner part of the solar system was formed from a gas reservoir that had been depleted in refractory dust or (ii) CI are enriched in refractory dust and are not representative of solar composition for refractory elements. Barrat J.A. et al. (2012) GCA 83, 79-92. Dauphas N., Pourmand A. (2015) GCA 163, 234-261. Pourmand et al. (2012) Chem. Geol. 291, 38-54.

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

PubMed

Lonial, Sagar; Dimopoulos, Meletios; Palumbo, Antonio; White, Darrell; Grosicki, Sebastian; Spicka, Ivan; Walter-Croneck, Adam; Moreau, Philippe; Mateos, Maria-Victoria; Magen, Hila; Belch, Andrew; Reece, Donna; Beksac, Meral; Spencer, Andrew; Oakervee, Heather; Orlowski, Robert Z; Taniwaki, Masafumi; Röllig, Christoph; Einsele, Hermann; Wu, Ka Lung; Singhal, Anil; San-Miguel, Jesus; Matsumoto, Morio; Katz, Jessica; Bleickardt, Eric; Poulart, Valerie; Anderson, Kenneth C; Richardson, Paul

2015-08-13

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

Aluminum reduction cell electrode

DOEpatents

Goodnow, Warren H.; Payne, John R.

1982-01-01

The invention is directed to cathode modules comprised of refractory hard metal materials, such as TiB.sub.2, for an electrolytic cell for the reduction of alumina wherein the modules may be installed and replaced during operation of the cell and wherein the structure of the cathode modules is such that the refractory hard metal materials are not subjected to externally applied forces or rigid constraints.

Lightweight alumina refractory aggregate. Final report

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

Swansiger, T.G.; Pearson, A.

1996-07-16

Objective was to develop a lightweight, high alumina refractory aggregate for use in various high performance insulating (low thermal conductivity) refractory applications (e.g., in the aluminium, glass, cement, and iron and steel industries). A new aggregate process was developed through bench and pilot-scale experiments involving extrusion of a blend of calcined and activated alumina powders and organic extrusion aids and binders. The aggregate, with a bulk density approaching 2.5 g/cc, exhibited reduced thermal conductivity and adequate fired strength compared to dense tabular aggregate. Refractory manufacturers were moderately enthusiastic over the results. Alcoa prepared an economic analysis for producing lightweight aggregate,more » based on a retrofit of this process into existing Alcoa production facilities. However, a new, competing lightweight aggregate material was developed by another company; this material (Plasmal{trademark})had a significantly more favorable cost base than the Alcoa/DOE material, due to cheap raw materials and fewer processing steps. In late 1995, Alcoa became a distributor of Plasmal. Alcoa estimated that {ge}75% of the market originally envisioned for the Alcoa/DOE aggregate would be taken by Plasmal. Hence, it was decided to terminate the contract without the full- scale demonstration.« less

Refractory materials from lunar resources

NASA Technical Reports Server (NTRS)

Fabes, B. D.; Poisl, W. H.

1991-01-01

Refractories - materials which are able to withstand extremely high temperatures - are sure to be an important part of any processing facility or human outpost which is built on Mars. Containers for processing lunar oxygen will need high temperature components. Fabrication of structural material from lunar resources need both containment vessels to hold high temperature melts and molds in which to form the final shapes. Certainly, it would be desirable to fabricate such vessels and molds on the Moon, rather than carrying them up from the Earth. At first glance, this might appear to be a trivial task, since the Moon's surface consists of a variety of refractory compositions. To turn the regolith into a useful fire brick or mold, however, will require water or other binders and additives which are likely to be in extremely short supply on the Moon. The steps needed to make fire bricks and molds for lunar-derived structural materials are examined, pointing out the critical steps and resources which will be needed. While these processes and applications may seem somewhat mundane, it is emphasized that it is precisely these rudimentary processes which must be mastered before discussing making aerobrakes, and other fancier refractories from lunar resources.

Porous Ceramic Cures at Moderate Temperatures, Is Good Heat Insulator

NASA Technical Reports Server (NTRS)

Eubanks, Alfred G.; Hunkeler, Ronald E.

1965-01-01

The problem: To develop a foamed-in-place refractory material that would provide good thermal insulation, mechanical support, and vibration shielding for enclosed objects at temperatures up to 30000 F. The preparation of conventional foamed refractory materials required long curing times (as much as 48 hours) and high temperatures (at least 700 F), rendering such materials unusable for in-place potting of heat-sensitive components. The solution: A foamed ceramic material that has the requisite thermal insulation and strength, and also displays other properties that suggest a wide range of applications.

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen.

PubMed

Musso, Maurizio; Messina, Giuseppe; Di Renzo, Nicola; Di Carlo, Paolo; Vitolo, Umberto; Scalone, Renato; Marcacci, Gianpaolo; Scalzulli, Potito R; Moscato, Tiziana; Matera, Rossella; Crescimanno, Alessandra; Santarone, Stella; Orciuolo, Enrico; Merenda, Anxur; Pavone, Vincenzo; Pastore, Domenico; Donnarumma, Daniela; Carella, Angelo M; Ciochetto, Chiara; Cascavilla, Nicola; Mele, Anna; Lanza, Francesco; Di Nicola, Massimo; Bonizzoni, Erminio; Pinto, Antonello

2016-01-01

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments. © 2015 John Wiley & Sons Ltd.

Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

PubMed

Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

2018-03-01

Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

Oxidation Behavior of a Refractory NbCrMo0.5Ta0.5TiZr Alloy

DTIC Science & Technology

2014-04-01

DANIEL J. EVANS, Chief Metals Branch Metals Branch Structural Materials Division...damage, is dif- ficult to achieve [2]. Thus, new metallic systems with higher melting points and a good balance of structural properties at high...has been considered to be the main issue during oxidation of conventional refractory alloys [14]. Heavy alloying of refractory metals with other

Aluminum reduction cell electrode

DOEpatents

Goodnow, W.H.; Payne, J.R.

1982-09-14

The invention is directed to cathode modules comprised of refractory hard metal materials, such as TiB[sub 2], for an electrolytic cell for the reduction of alumina wherein the modules may be installed and replaced during operation of the cell and wherein the structure of the cathode modules is such that the refractory hard metal materials are not subjected to externally applied forces or rigid constraints. 9 figs.

Highly Refractory Porous Ceramics,

DTIC Science & Technology

1979-03-14

some cases is not desirable. A uniform distribution of tem- peratures in the melting ch the use of thermally insulating materials, i. e. stability of...materials with micropores that a are inaccessible to penetration by sl s and other melts , which appears, how- ever, to be a very difficult problem...requirements for refractoriness, chemical stability, etc. In accordance with GOST 5040-68, maximum temperatures were established for the melting chamber

Development of a New Ferrous Aluminosilicate Refractory Material for Investment Casting of Aluminum Alloys

NASA Astrophysics Data System (ADS)

Yuan, Chen; Jones, Sam; Blackburn, Stuart

2012-12-01

Investment casting is a time-consuming, labour intensive process, which produces complex, high value-added components for a variety of specialised industries. Current environmental and economic pressures have resulted in a need for the industry to improve current casting quality, reduce manufacturing costs and explore new markets for the process. Alumino-silicate based refractories are commonly used as both filler and stucco materials for ceramic shell production. A new ceramic material, norite, is now being produced based on ferrous aluminosilicate chemistry, having many potential advantages when used for the production of shell molds for casting aluminum alloy. This paper details the results of a direct comparison made between the properties of a ceramic shell system produced with norite refractories and a typical standard refractory shell system commonly used in casting industry. A range of mechanical and physical properties of the systems was measured, and a full-scale industrial casting trial was also carried out. The unique properties of the norite shell system make it a promising alternative for casting aluminum based alloys in the investment foundry.

Refractory metals for ARPS AMTEC cells

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

Svedberg, R.C.; Sievers, R.C.

1998-07-01

Alkali Metal Thermal-to-Electric Converter (AMTEC) cells for the Advanced Radioisotope Power Systems (ARPS) program are being developed with refractory metals and alloys as the basic structural materials. AMTEC cell efficiency increases with cell operating temperature. For space applications, long term reliability and high efficiency are essential and refractory metals were selected because of their high temperature strength, low vapor pressure, and compatibility with sodium. However, refractory metals are sensitive to oxygen, nitrogen and hydrogen contamination and refractory metal cells cannot be processed in air. Because of this sensitivity, new manufacturing and processing techniques are being developed. In addition to structuralmore » elements, development of other refractory metal components for the AMTEC cells, such as the artery and evaporator wicks, pinchoff tubes and feedthroughs are required. Changes in cell fabrication techniques and processing procedures being implemented to manufacture refractory metal cells are discussed.« less

Preparation of MgO-SnO2-TiO2 Materials and Their Corrosion in Na3AlF6-AlF3-K3AlF6 Bath

NASA Astrophysics Data System (ADS)

Xu, Yibiao; Li, Yawei; Sang, Shaobai; Ren, Bo; Qin, Qingwei; Yang, Jianhong

2015-01-01

New types of refractory materials need to be developed for designing the so-called ledge-free sidewalls of the Hall-Héroult cell for aluminum extraction, which are currently constructed using Si3N4 bonded SiC refractories. In the present paper, MgO-based materials as potential candidate sidewalls were prepared using fused magnesia, tin dioxide, and anatase powder as starting materials. The reaction sintering process of the MgO-SnO2-TiO2 materials was investigated by means of X-ray diffraction and scanning electron microscope (SEM). All the specimens were corroded in a Na3AlF6-AlF3-K3AlF6 bath to assess the electrolyte corrosion resistance. The results show that reaction sintering occurs in the MgO-SnO2-TiO2 system in the range of 1373 K to 1873 K (1100 °C to 1600 °C). Firstly, MgO reacts separately with TiO2 and SnO2 to produce the Mg2TiO4 and Mg2SnO4 phases at 1373 K (1100 °C), which in turn react to form the Mg2Ti x Sn1-x O4 composite spinel at temperatures above 1373 K (1100 °C). All the specimens prepared are composed of the composite spinel and periclase phases. Increasing the SnO2 addition from 2 to 10 wt pct enhances densification of the specimens, which is accompanied by the formation of homogeneously distributed composite spinels in the MgO matrix, but the density of the specimen decreases when the amount of SnO2 added is higher than 10 wt pct due to larger volume expansion and agglomeration of the composite spinel. The MgO-SnO2-TiO2 refractories prepared exhibit good corrosion resistance to the electrolyte melts owing to their high density and formation of the composite spinel in the specimens. Their corrosion resistance increases progressively with the increase in the SnO2 addition owing to the formation of more chemically stable composite spinel.

Surface treatment of alumina-based ceramics using combined laser sources

NASA Astrophysics Data System (ADS)

Triantafyllidis, D.; Li, L.; Stott, F. H.

2002-01-01

Alumina-based refractory materials are extensively used as linings in incinerators and furnaces. These materials are subject to molten salt corrosion and chemical degradation because of the existence of porosity and material inhomogeneity. Efforts to improve the performance of these materials have so far concentrated mainly on the optimisation of the manufacturing processes (e.g. producing denser refractory bricks) and in-service monitoring. Laser surface treatment has also been used to improve performance. The main problem identified with laser surface treatment is solidification cracking due to the generation of very large temperature gradients. The aim of this paper is to investigate the surface modification of alumina-based ceramics by using two combined laser sources in order to control the thermal gradients and cooling rates during processing so that crack formation can be eliminated. The material under investigation is 85% alumina refractory ceramic, used as lining material in incineration plants. The surface morphology and cross-section of the treated samples are analysed using optical and scanning electron microscopy (SEM) and compared with single laser beam treated samples.

Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine.

PubMed

Albany, Costantine; Hever-Jardine, Mary P; von Herrmann, Katherine M; Yim, Christina Y; Tam, Janice; Warzecha, Joshua M; Shin, Leah; Bock, Sarah E; Curran, Brian S; Chaudhry, Aneeq S; Kim, Fred; Sandusky, George E; Taverna, Pietro; Freemantle, Sarah J; Christensen, Brock C; Einhorn, Lawrence H; Spinella, Michael J

2017-01-10

Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients.

Catalytic, hollow, refractory spheres, conversions with them

NASA Technical Reports Server (NTRS)

Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor); Lee, Mark C. (Inventor); Kendall, Jr., James M. (Inventor)

1989-01-01

Improved, heterogeneous, refractory catalysts are in the form of gas-impervious, hollow, thin-walled spheres (10) suitable formed of a shell (12) of refractory such as alumina having a cavity (14) containing a gas at a pressure greater than atmospheric pressure. The wall material may be itself catalytic or a catalytically active material coated onto the sphere as a layer (16), suitably platinum or iron, which may be further coated with a layer (18) of activator or promoter. The density of the spheres (30) can be uniformly controlled to a preselected value within .+-.10 percent of the density of the fluid reactant such that the spheres either remain suspended or slowly fall or rise through the liquid reactant.

Catalytic, hollow, refractory spheres

NASA Technical Reports Server (NTRS)

Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor); Lee, Mark C. (Inventor); Kendall, Jr., James M. (Inventor)

1987-01-01

Improved, heterogeneous, refractory catalysts are in the form of gas-impervious, hollow, thin-walled spheres (10) suitable formed of a shell (12) of refractory such as alumina having a cavity (14) containing a gas at a pressure greater than atmospheric pressure. The wall material may be itself catalytic or a catalytically active material coated onto the sphere as a layer (16), suitably platinum or iron, which may be further coated with a layer (18) of activator or promoter. The density of the spheres (30) can be uniformly controlled to a preselected value within .+-.10 percent of the density of the fluid reactant such that the spheres either remain suspended or slowly fall or rise through the liquid reactant.

Method for hot pressing irregularly shaped refractory articles

DOEpatents

Steinkamp, William E.; Ballard, Ambrose H.

1982-01-01

The present invention is directed to a method for hot pressing irregularly haped refractory articles with these articles of varying thickness being provided with high uniform density and dimensional accuracy. Two partially pressed compacts of the refractory material are placed in a die cavity between displaceable die punches having compact-contacting surfaces of the desired article configuration. A floating, rotatable block is disposed between the compacts. The displacement of the die punches towards one another causes the block to rotate about an axis normal to the direction of movement of the die punches to uniformly distribute the pressure loading upon the compacts for maintaining substantially equal volume displacement of the powder material during the hot pressing operation.

Preliminary Investigations of Joining Technologies for Attaching Refractory Metals to Ni-Based Superalloys

NASA Technical Reports Server (NTRS)

Gould, Jerry E.; Ritzert, Frank J.; Loewenthal, William S.

2006-01-01

In this study, a range of joining technologies has been investigated for creating attachments between refractory metal and Ni-based superalloys. Refractory materials of interest include Mo-47%Re, T-111, and Ta-10%W. The Ni-based superalloys include Hastelloy X and MarM 247. During joining with conventional processes, these materials have potential for a range of solidification and intermetallic formation-related defects. For this study, three non-conventional joining technologies were evaluated. These included inertia welding, electro-spark deposition (ESD) welding, and magnetic pulse welding (MPW). The developed inertia welding practice closely paralleled that typically used for the refractory metals alloys. Metallographic investigations showed that forging during inertia welding occurred predominantly on the nickel base alloy side. It was also noted that at least some degree of forging on the refractory metal side of the joint was necessary to achieve consistent bonding. Both refractory metals were readily weldable to the Hastelloy X material. When bonding to the MarM 247, results were inconsistent. This was related to the higher forging temperatures of the MarM 247, and subsequent reduced deformation on that material during welding. ESD trials using a Hastelloy X filler were successful for all material combinations. ESD places down very thin (5- to 10- m) layers per pass, and interactions between the substrates and the fill were limited (at most) to that layer. For the refractory metals, the fill only appeared to wet the surface, with minimal dilution effects. Microstructures of the deposits showed high weld metal integrity with maximum porosity on the order of a few percent. Some limited success was also obtained with MPW. In these trials, only the T-111 tubes were used. Joints were possible for the T-111 tube to the Hastelloy X bar stock, but the stiffness of the tube (resisting collapse) necessitated the use of very high power levels. These power levels resulted in damage to the equipment (concentrator) during welding. It is of note that the joint made showed the typical wavy bond microstructure associated with magnetic pulse/explosion bond joints. Joints were not possible between the T-111 tube and the MarM 247 bar stock. In this case, the MarM 247 shattered before sufficient impact forces could be developed for bonding.

Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma

PubMed Central

Younes, Anas; Gopal, Ajay K.; Smith, Scott E.; Ansell, Stephen M.; Rosenblatt, Joseph D.; Savage, Kerry J.; Ramchandren, Radhakrishnan; Bartlett, Nancy L.; Cheson, Bruce D.; de Vos, Sven; Forero-Torres, Andres; Moskowitz, Craig H.; Connors, Joseph M.; Engert, Andreas; Larsen, Emily K.; Kennedy, Dana A.; Sievers, Eric L.; Chen, Robert

2012-01-01

Purpose Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. Patients and Methods In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. Results The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. Conclusion The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy. PMID:22454421

A phase II study of high-dose celecoxib and metronomic 'low-dose' cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma.

PubMed

El Bary, Naser Abd; Hashem, Tarek; Metwally, Hasan; Ghany, Ashraf Abd; El Mageed, Hager Abd

2010-01-01

Relapsed, histologically aggressive non-Hodgkin lymphoma (NHL) has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies (as long as one included an anthracycline) and were not candidates for bone marrow transplantation. They received oral cyclophosphamide (50 mg every day), oral methotrexate (2.5 mg 4 times/week) and high-dose oral celecoxib (400 mg twice daily) until there was disease progression or unacceptable toxicity. All 41 patients (median age, 56 years) were evaluable for toxicity and response, with a median follow up of 9.1 months (range, 4-35 months). At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue (61%), nausea (22%), neutropenia (19.5%), and anemia (22%). In 31.7% there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months. We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemo-immunotherapy combinations should be explored prior to a decision on metronomic chemotherapy.

Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405).

PubMed

Isozaki, Hideko; Hotta, Katsuyuki; Ichihara, Eiki; Takigawa, Nagio; Ohashi, Kadoaki; Kubo, Toshio; Ninomiya, Takashi; Ninomiya, Kiichiro; Oda, Naohiro; Yoshioka, Hiroshige; Ichikawa, Hirohisa; Inoue, Masaaki; Takata, Ichiro; Shibayama, Takuo; Kuyama, Shoichi; Sugimoto, Keisuke; Harada, Daijiro; Harita, Shingo; Sendo, Toshiaki; Tanimoto, Mitsune; Kiura, Katsuyuki

2016-11-01

Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory non-small-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with non-small-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided α of 0.05, β of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK + non-small-cell lung cancer even in the alectinib-refractory setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Low-Chrome/Chrome Free Refractories for Slagging Gasifiers

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

Bennett, J.P.; Kwong, K.-S.; Powell, C.P.

2007-01-01

Gasifiers are containment vessels used to react carbon-containing materials with oxygen and water, producing syngas (CO and H2) that is used in chemical and power production. It is also a potential source of H2 in a future hydrogen economy. Air cooled slagging gasifiers are one type of gasifier, operating at temperatures from 1275-1575º C and at pressures of 400 psi or higher. They typically use coal or petroleum coke as the carbon source, materials which contain ash impurities that liquefy at the gasification temperatures, producing liquid slag in quantities of 100 or more tons/day, depending on the carbon fed ratemore » and the percent ash present in the feedstock. The molten slag is corrosive to refractory linings, causing chemical dissolution and spalling. The refractory lining is composed of chrome oxide, alumina, and zirconia; and is replaced every 3-24 months. Gasifier users would like greater on-line availability and reliability of gasifier liners, something that has impacted gasifier acceptance by industry. Research is underway at NETL to improve refractory service life and to develop a no-chrome or low-chrome oxide alternative refractory liner. Over 250 samples of no- or low-chrome oxide compositions have been evaluated for slag interactions by cup testing; with potential candidates for further studies including those with ZrO2, Al2O3, and MgO materials. The development of improved liner materials is necessary if technologies such as IGCC and DOE’s Near Zero Emissions Advanced Fossil Fuel Power Plant are to be successful and move forward in the marketplace.« less

The Quantitative Significance of Nondestructive Evaluation of Graphite and Ceramic Materials.

DTIC Science & Technology

NONDESTRUCTIVE TESTING), (* GRAPHITE , (*BORIDES, NONDESTRUCTIVE TESTING), (*REFRACTORY MATERIALS, NONDESTRUCTIVE TESTING), DEFECTS(MATERIALS), TENSILE PROPERTIES, RADIOGRAPHY, ULTRASONIC PROPERTIES, DENSITY.

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

ClinicalTrials.gov

2017-12-11

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Materials interactions between the thermoelectric converter and the 5kwe reactor system

NASA Technical Reports Server (NTRS)

Ferry, P. B.

1973-01-01

The integration of a compact thermoelectric converter with a 5-kwe reactor system is described. Material interaction uncertainties study is also presented. This includes degradation of the required austenitic - refractory metal transition joint during operation at high temperatures; loss of corrosion resistance; embrittlement by the presence of hydrogen; and loss of design margin by transport of interstitial elements. Analysis and limited experimental evidence indicate that these potential materials interactions can be adequately controlled. Group 5-2 refractory metals can be utilized without unacceptable adverse effect on system reliability.

Launch Pad Flame Trench Refractory Materials

NASA Technical Reports Server (NTRS)

Calle, Luz M.; Hintze, Paul E.; Parlier, Christopher R.; Bucherl, Cori; Sampson, Jeffrey W.; Curran, Jerome P.; Kolody, Mark; Perusich, Steve; Whitten, Mary

2010-01-01

The launch complexes at NASA's John F. Kennedy Space Center (KSC) are critical support facilities for the successful launch of space-based vehicles. These facilities include a flame trench that bisects the pad at ground level. This trench includes a flame deflector system that consists of an inverted, V-shaped steel structure covered with a high temperature concrete material five inches thick that extends across the center of the flame trench. One side of the "V11 receives and deflects the flames from the orbiter main engines; the opposite side deflects the flames from the solid rocket boosters. There are also two movable deflectors at the top of the trench to provide additional protection to shuttle hardware from the solid rocket booster flames. These facilities are over 40 years old and are experiencing constant deterioration from launch heat/blast effects and environmental exposure. The refractory material currently used in launch pad flame deflectors has become susceptible to failure, resulting in large sections of the material breaking away from the steel base structure and creating high-speed projectiles during launch. These projectiles jeopardize the safety of the launch complex, crew, and vehicle. Post launch inspections have revealed that the number and frequency of repairs, as well as the area and size of the damage, is increasing with the number of launches. The Space Shuttle Program has accepted the extensive ground processing costs for post launch repair of damaged areas and investigations of future launch related failures for the remainder of the program. There currently are no long term solutions available for Constellation Program ground operations to address the poor performance and subsequent failures of the refractory materials. Over the last three years, significant liberation of refractory material in the flame trench and fire bricks along the adjacent trench walls following Space Shuttle launches have resulted in extensive investigations of failure mechanisms, load response, ejected material impact evaluation, and repair design analysis (environmental and structural assessment, induced environment from solid rocket booster plume, loads summary, and repair integrity), assessment of risk posture for flame trench debris, and justification of flight readiness rationale. Although the configuration of the launch pad, water and exhaust direction, and location of the Mobile Launcher Platform between the flame trench and the flight hardware should protect the Space Vehicle from debris exposure, loss of material could cause damage to a major element of the ground facility (resulting in temporary usage loss); and damage to other facility elements is possible. These are all significant risks that will impact ground operations for Constellation and development of new refractory material systems is necessary to reduce the likelihood of the foreign object debris hazard during launch. KSC is developing an alternate refractory material for the launch pad flame trench protection system, including flame deflector and flame trench walls, that will withstand launch conditions without the need for repair after every launch, as is currently the case. This paper will present a summary of the results from industry surveys, trade studies, life cycle cost analysis, and preliminary testing that have been performed to support and validate the development, testing, and qualification of new refractory materials.

[State of the art treatment of progressive or refractory multiple myeloma].

PubMed

Schmidt-Wolf, I G H; Straka, C; Scheid, C; Einsele, H; Goldschmidt, H; Engelhardt, M

2014-10-01

Multiple myeloma (MM) is with an incidence of 4-6/100 000 inhabitants a fairly frequent malignancy of B cells. The incidence increases markedly with age. In this review changes in the treatment of relapsed / refractory myeloma during the last decade have been analysed. The present standard of care in the progressive or refractory myeloma was elaborated by the working group "Refractory Multiple Myeloma" using an extensive literature search for studies published between 2003 and 2013. Outside of clinical trials, high-dose therapy with stem cell transplantation is recommended in fit patients up to 75 years without significant comorbidities. Ongoing studies address the question about the least toxic and the most effective treatment. Therefore, inclusion of patients in therapeutic trials and use of novel agent combinations is highly recommended, e.g. with 3(rd) generation-IMIDs (pomalidomide), new proteasome inhibitors, such as carfilzomib, ixazomib or oprozomib, antibodies, such as elotuzumab, daratumumab or SAR650984, siltuximab, tabalumab, denosumab, romosozumab, BTK-, HSP-inhibitors and other innovative phase I/II agents. Based on new insights in the pathogenesis of the disease, treatment options for MM have changed significantly in recent years. There is a significantly larger treatment diversity, i.e. more MM-active agents and combinations are available today. Even with relapsed MM, patients with the disease often live longer and have fewer complications. © Georg Thieme Verlag KG Stuttgart · New York.

Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome.

PubMed

Sorigue, Marc; Mercadal, Santiago; Alonso, Sara; Fernández-Álvarez, Ruben; García, Olga; Moreno, Miriam; Pomares, Helena; Alcoceba, Miguel; González-García, Esther; Motlló, Cristina; González-Barca, Eva; Martin, Alejandro; Sureda, Anna; Caballero, Dolores; Ribera, Josep-María; Sancho, Juan-Manuel

2017-12-01

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and β2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum β2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory. Copyright © 2017 John Wiley & Sons, Ltd.

System and method for producing metallic iron

DOEpatents

Englund, David J.; Schlichting, Mark; Meehan, John; Crouch, Jeremiah; Wilson, Logan

2014-07-29

A method of production of metallic iron nodules comprises assembling a hearth furnace having a moveable hearth comprising refractory material and having a conversion zone and a fusion zone, providing a hearth material layer comprising carbonaceous material on the refractory material, providing a layer of reducible material comprising and iron bearing material arranged in discrete portions over at least a portion of the hearth material layer, delivering oxygen gas into the hearth furnace to a ratio of at least 0.8:1 ponds of oxygen to pounds of iron in the reducible material to heat the conversion zone to a temperature sufficient to at least partially reduce the reducible material and to heat the fusion zone to a temperature sufficient to at least partially reduce the reducible material, and heating the reducible material to form one or more metallic iron nodules and slag.

Chemical properties and methods of analysis of refractory compounds

NASA Technical Reports Server (NTRS)

Samsonov, G. V. (Editor); Frantsevich, I. N. (Editor); Yeremenko, V. N. (Editor); Nazarchuk, T. N. (Editor); Popova, O. I. (Editor)

1978-01-01

Reactions involving refractory metals and the alloys based on them are discussed. Chemical, electrochemical, photometric, spectrophotometric, and X-ray analysis are among the methods described for analyzing the results of the reactions and for determining the chemical properties of these materials.

Synthetic Coal Slag Infiltration into Varying Refractory Materials

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

Kaneko, Tetsuya K; Thomas, Hugh; Bennett, James P

The infiltrations of synthetic coal slag into 99%Al{sub 2}O{sub 3}, 85%Al{sub 2}O{sub 3}–15%SiO{sub 2}, and 90%Cr{sub 2}O{sub 3}–10%Al{sub 2}O{sub 3} refractories with a temperature gradient induced along the penetration direction were compared to one another. The infiltrating slag was synthesized with a composition that is representative of an average of the ash contents from U S coal feedstock. Experiments were conducted with a hot-face temperature of 1450°C in a CO/CO{sub 2} atmosphere. Minimal penetration was observed in the 90%Cr{sub 2}O{sub 3}–10%Al{sub 2}O{sub 3} material because interactions between the refractory and the slag produced a protective layer of FeCr{sub 2}O{sub 4},more » which impeded slag flow into the bulk of the refractory. After 5 h, the 99%Al{sub 2}O{sub 3} sample exhibited an average penetration of 12.7 mm whereas the 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} sample showed 3.8 mm. Slag infiltrated into the 99%Al{sub 2}O{sub 3} and 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} refractory systems by dissolving the respective refractories' matrix materials, which consist of fine Al{sub 2}O{sub 3} particles and an amorphous alumino-silicate phase. Due to enrichment in SiO{sub 2}, a network-former, infiltration into the 85%Al{sub 2}O{sub 3}–15%SiO{sub 2} system yielded a higher viscosity slag and hence, a shallower penetration depth. The results suggest that slag infiltration can be limited by interactions with the refractory through the formation of either a solid layer that physically impedes fluid flow or a more viscous slag that retards infiltration.« less

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

PubMed Central

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Targeting MTA1/HIF-1a signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

USDA-ARS?s Scientific Manuscript database

The metastasis-associated protein 1(MTA1)/ histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer. In our previous studies, we found a significantly increased MTA1 expression in a prostate-spec...

Experimental investigation of refractory metals in the premelting region during fast heating

NASA Astrophysics Data System (ADS)

Senchenko, V. N.; Belikov, R. S.; Popov, V. S.

2015-11-01

This work demonstrates experimental possibility of investigation of high refractory materials around its melting point, particularly in premelting region with high accuracy. In this article authors describe the developed experimental setup based on rapid resistive self-heating of a sample by a large current pulse generated by a capacitor discharge circuit that allow fast pulse interruption by temperature feedback signal. The sample temperature was measured with a two-channel microsecond radiation pyrometer. Preliminary experiments were conducted on tantalum and molybdenum at heating speed of 108 K/s. The method allows investigating thermophysical properties of refractory conductive materials such as melting temperature, melting heat, specific resistivity, specific enthalpy and specific heat capacity in solid and liquid phase, especially in premelting area.

Making Space Travel to Jupiter Possible

NASA Technical Reports Server (NTRS)

Barker, Samuel P.

2004-01-01

From man landing on the moon to a simple satellite being launched into orbit, many incredible space accomplishments have been witnessed by us all. However, what goes un-noticed to the common man is the extensive research and testing that lasts months, years, and even decades. Much of this required research just so happens to take place in the corridors of the Glen Research Center building number 49. In the Advanced Materials division of G.R.C., a number of researchers have the responsibility of discovering which metal, ceramic, or polymer is best for a specific application. Under the guidance of mentor extraordinaire Frank Ritzert, I am involved in many critical projects dealing with refractory metals, two of which I will mention in this report. The Jupiter Icy Moons Orbiter (JIMO) project actually was under full swing back in the 50's and early 60's. To enable the 14 year trek to the icy moons of Europa, Callisto, and Ganymede, nuclear propulsion methods were selected. Due to the extreme temperature of the reactor and the extended time period, a refractory metal would need to be implemented. After years of research and progress, the program was suddenly canceled. About a decade ago, the JIMO project was re-instated and now has a goal for departure around 2014. However, a few obstacles lie in our way concerning the use of refractory metals. In certain areas of the orbiter a joint is required between the refractories and other less dense metals. Two of these joints are with nickel based super alloys. Being an intern for Frank Ritzert, the refractory metals expert, I have the opportunity to develop the best method to braze refractory metals to Nickel 201. This involves the actual brazing, electron microscopy and reporting the results. My second project involves a certain part of the orbiter where Niobium 1Zirconium, a refractory metal, is joined with Hastelloy-X a Ni based metal. Small quantities of oxygen, helium and other impurities in the Ni alloy could diffuse into the Nb1Zr causing imbrittlement and possibly major failure. I will be testing the effects of Hast-X on Nb1Zr in a high temperature for 10, 50, 100, and 500 hours. After the samples are run through the heat treatment, strength and chemistry will be tested and reported. My appreciation for the research that goes behind every project has and will continue to grow. By digging through old documents written in the 50's and 60's, scouring through forgotten closets, and learning from those with experience in the refractory metals, I am bound to have an incredible learning experience here at NASA.

[The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistiocytosis].

PubMed

Tong, Chun-Rong; Liu, Hong-Xing; Xie, Jian-Jun; Wang, Fang; Cai, Peng; Wang, Hui; Zhu, Juan; Teng, Wen; Zhang, Xian; Yang, Jun-Fang; Zhang, Ya-Li; Fei, Xin-Hong; Zhao, Jie; Yin, Yu-Ming; Wu, Tong; Wang, Jing-Bo; Sun, Yuan; Liu, Rong; Shi, Xiao-Dong; Lu, Dao-Pei

2011-04-01

To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11, XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH (EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH), 1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t(15;17) (q22;q25) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH, some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

PubMed

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

2018-01-01

Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

PubMed Central

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I.

2018-01-01

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable. PMID:29344270

Pumped lithium loop test to evaluate advanced refractory metal alloys and simulated nuclear fuel elements

NASA Technical Reports Server (NTRS)

Brandenburf, G. P.; Hoffman, E. E.; Smith, J. P.

1974-01-01

The performance was determined of refractory metal alloys and uranium nitride fuel element specimens in flowing 1900F (1083C) lithium. The results demonstrate the suitability of the selected materials to perform satisfactorily from a chemical compatibility standpoint.

A PHASE II TRIAL OF THALIDOMIDE IN PATIENTS WITH REFRACTORY ENDOMETRIAL CANCER AND CORRELATION WITH ANGIOGENESIS BIOMARKERS: A GYNECOLOGIC ONCOLOGY GROUP STUDY

PubMed Central

McMeekin, D. Scott; Sill, Michael W.; Benbrook, Doris; Darcy, Kathleen M.; Stearns-Kurosawa, Deborah J.; Eaton, Lynne; Yamada, S. Diane

2007-01-01

Objectives A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome. Methods Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens. Results Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival were 1.7 months and 6.3 months, respectively. No grade 4 toxicities were observed. Common grade 3 toxicities included hematologic (n=3), cardiovascular (n=3), constitutional (n=3), and neurologic (n=4). Thalidomide did not decrease VEGF or bFGF levels but reduced sEPCR levels in serum. Elevated plasma vascular endothelial growth factor levels were associated with increased risk of progression and death. Conclusions Thalidomide demonstrated limited ability to delay progression (as measured by PFS at 6 months), produce objective responses or reduce angiogenic marker levels in chemotherapy refractory endometrial cancer. VEGF level appears to be prognostically significant in such patients, independent of thalidomide treatment. PMID:17306350

Plasma-Sprayed Refractory Oxide Coatings on Silicon-Base Ceramics

NASA Technical Reports Server (NTRS)

Tewari, Surendra

1997-01-01

Silicon-base ceramics are promising candidate materials for high temperature structural applications such as heat exchangers, gas turbines and advanced internal combustion engines. Composites based on these materials are leading candidates for combustor materials for HSCT gas turbine engines. These materials possess a combination of excellent physical and mechanical properties at high temperatures, for example, high strength, high toughness, high thermal shock resistance, high thermal conductivity, light weight and excellent oxidation resistance. However, environmental durability can be significantly reduced in certain conditions such as when molten salts, H2 or water vapor are present. The oxidation resistance of silicon-base materials is provided by SiO2 protective layer. Molten salt reacts with SiO2 and forms a mixture of SiO2 and liquid silicate at temperatures above 800C. Oxygen diffuses more easily through the chemically altered layer, resulting in a catastrophic degradation of the substrate. SiC and Si3N4 are not stable in pure H2 and decompose to silicon and gaseous species such as CH4, SiH, SiH4, N2, and NH3. Water vapor is known to slightly increase the oxidation rate of SiC and Si3N4. Refractory oxides such as alumina, yttria-stabilized zirconia, yttria and mullite (3Al2O3.2SiO2) possess excellent environmental durability in harsh conditions mentioned above. Therefore, refractory oxide coatings on silicon-base ceramics can substantially improve the environmental durability of these materials by acting as a chemical reaction barrier. These oxide coatings can also serve as a thermal barrier. The purpose of this research program has been to develop refractory oxide chemical/thermal barrier coatings on silicon-base ceramics to provide extended temperature range and lifetime to these materials in harsh environments.

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

PubMed

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

Outcome of children with relapsed or refractory neuroblastoma: A meta-analysis of ITCC/SIOPEN European phase II clinical trials.

PubMed

Moreno, Lucas; Rubie, Herve; Varo, Amalia; Le Deley, Marie Cecile; Amoroso, Loredana; Chevance, Aurelie; Garaventa, Alberto; Gambart, Marion; Bautista, Francisco; Valteau-Couanet, Dominique; Geoerger, Birgit; Vassal, Gilles; Paoletti, Xavier; Pearson, Andrew D J

2017-01-01

Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and data about outcomes including progression-free survival (PFS) in these patients are scarce. A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed. Individual patient data with extended follow-up were collected from the trial databases after publication to describe trial outcomes (response rate, clinical benefit ratio, duration of treatment, PFS, and overall survival [OS]). Characteristics of subjects with relapsed/refractory neuroblastoma were compared. Data from 71 children and adolescents with relapsed/refractory neuroblastoma were collected. Response definitions were not homogeneous in the three trials. Patients were on study for a median of 3.5 months (interquartile range [IQR] 1.9-6.2). Of those, 35.2% achieved a complete or partial response, 26.3% experienced a response after more than two cycles, and 23.9% received more than six cycles. Median PFS from study entry for all, refractory, and relapsed patients was 6.4 ± 1.0, 12.5 ± 6.8, and 5.7 ± 1.0 months, respectively (P = 0.006). Median OS from study entry for all, refractory, and relapsed patients was 16.1 ± 4.3, 27.9 ± 20.2, and 11.0 ± 1.6 months, respectively (P = 0.03). Baseline data for response rate, clinical benefit ratio, duration of treatment, PFS, and OS were provided. Two subpopulations (relapsed/refractory) were clearly distinct and should be included in the interpretation of all trials. These results should help informing the design of forthcoming studies in relapsed/refractory neuroblastoma. © 2016 Wiley Periodicals, Inc.

Phase II study of DFP-10917, a deoxycytidine analog, given by 14-day continuous intravenous infusion for chemotherapy-refractory advanced colorectal cancer.

PubMed

Mehrvarz Sarshekeh, Amir; Xiong, Henry Q; Iizuka, Kenzo; Hochster, Howard S; Kopetz, Scott

2018-06-13

Background DFP-10917 is a cytotoxic deoxycytidine analogue that causes DNA fragmentation, G 2 /M-phase arrest, and apoptosis. This agent has been shown to have antitumor activity against colorectal cancer (CRC) in preclinical studies and to be tolerable in patients. The purpose of our phase II trial was to evaluate the safety, efficacy and pharmacogenomics of DFP-10917 as well as DNA damage studies in patients with advanced CRC refractory to cytotoxic chemotherapy. Methods In this single-arm, Simon two-stage, phase II trial, patients with chemotherapy-refractory advanced CRC received 2.0 mg/m 2 /day DFP-10917 via 14-day continuous infusion. Enrollment criteria included age ≥ 18 years, Eastern Cooperative Oncology Group status of 0 or 1, and adequate organ function. The primary endpoint was 3-month progression-free survival, defined as the proportion of patients who did not have progressive disease or death within 3 months of starting therapy. All patients who received any amount of DFP-10917 were included in the safety analysis. DNA damage study was assessed by comet assay. Results Of 28 patients initially enrolled, 26 received DFP-10917. Three patients (12%) were progression free at 3 months. The median progression-free survival was 1.3 months (95% confidence interval, 1.3-1.6 months). There were no complete or partial responses. Most patients (n = 20, 77%) had progressive disease, and only six (23%) had stable disease at any time. The trial was terminated according to the pre-planned stopping rule. The most frequent (≥5%) medication-related grade 3 or higher adverse events were neutropenia (n = 10, 38%), fatigue (n = 4, 15%), anemia (n = 3, 12%), and leukopenia (n = 3, 12%). DNA strand-breaks were detected after infusion (medians of % tail intensity were 2.89 and 12.64 on day 1 and day 15, respectively, p < 0.001, sign test). Conclusion Overall, single-agent DFP-10917 did not show meaningful antitumor activity in chemotherapy-refractory advanced CRC. The safety profile of DFP-10917 was tolerable and similar to that observed in earlier clinical studies.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, David H.; Ulrich, Klaus H.

1998-01-01

A refractory-lined high temperature reaction vessel comprises a refractory ring lining constructed of refractory brick, a cooler, and a heat transfer medium disposed between the refractory ring lining and the cooler. The refractory brick comprises magnesia (MgO) and graphite. The heat transfer medium contacts the refractory brick and a cooling surface of the cooler, and is composed of a material that accommodates relative movement between the refractory brick and the cooler. The brick is manufactured such that the graphite has an orientation providing a high thermal conductivity in the lengthwise direction through the brick that is higher than the thermal conductivity in directions perpendicular to the lengthwise direction. The graphite preferably is flake graphite, in the range of about 10 to 20 wt %, and has a size distribution selected to provide maximum brick density. The reaction vessel may be used for performing a reaction process including the steps of forming a layer of slag on a melt in the vessel, the slag having a softening point temperature range, and forming a protective frozen layer of slag on the interior-facing surface of the refractory lining in at least a portion of a zone where the surface contacts the layer of slag, the protective frozen layer being maintained at or about the softening point of the slag.

Influence of porosity and composition of supports on the methanogenic biofilm characteristics developed in a fixed bed anaerobic reactor.

PubMed

Picanço, A P; Vallero, M V; Gianotti, E P; Zaiat, M; Blundi, C E

2001-01-01

This paper reports on the influence of the material porosity on the anaerobic biomass adhesion on four different inert matrices: polyurethane foam, PVC, refractory brick and special ceramic. The biofilm development was performed in a fixed-bed anaerobic reactor containing all the support materials and fed with a synthetic wastewater containing protein, lipids and carbohydrates. The data obtained from microscopic analysis and kinetic assays indicated that the material porosity has a crucial importance in the retention of the anaerobic biomass. The polyurethane foam particles and the special ceramic were found to present better retentive properties than the PVC and the refractory brick. The large specific surface area, directly related to material porosity, is fundamental to provide a large amount of attached biomass. However, different supports can provide specific conditions for the adherence of distinct microorganism types. The microbiological exams revealed a distinction in the support colonization. A predominance of methanogenic archaeas resembling Methanosaeta was observed both in the refractory brick and the special ceramic. Methanosarcina-like microorganisms were predominant in the PVC and the polyurethane foam matrices.

A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma

PubMed Central

Xie, Wanling; Jagannath, Sundar; Jakubowiak, Andrzej; Lonial, Sagar; Raje, Noopur S.; Alsina, Melissa; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Mazumder, Amitabha; Vesole, David H.; Kaufman, Jonathan L.; Colson, Kathleen; McKenney, Mary; Lunde, Laura E.; Feather, John; Maglio, Michelle E.; Warren, Diane; Francis, Dixil; Hideshima, Teru; Knight, Robert; Esseltine, Dixie-Lee; Mitsiades, Constantine S.; Weller, Edie; Anderson, Kenneth C.

2014-01-01

In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209. PMID:24429336

Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

PubMed

London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

2017-12-15

Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial enrollment. This recent COG cohort of patients with recurrent/refractory neuroblastoma is inclusive and representative. To the authors' knowledge, the current study is the first meta-analysis of PFS, TTP, and OS within the context of modern therapy. These results will inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization. Cancer 2017;123:4914-23. © 2017 American Cancer Society. © 2017 American Cancer Society.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

Oxygen isotope exchange between refractory inclusion in Allende and solar nebula gas.

PubMed

Yurimoto, H; Ito, M; Nagasawa, H

1998-12-04

A calcium-aluminum-rich inclusion (CAI) from the Allende meteorite was analyzed and found to contain melilite crystals with extreme oxygen-isotope composition (approximately 5 percent oxygen-16 enrichment relative to terrestrial oxygen-16). Some of the melilite is also anomalously enriched in oxygen-16 compared with oxygen isotopes measured in other CAIs. The oxygen isotopic variation measured among the minerals (melilite, spinel, and fassaite) indicates that crystallization of the CAI started from oxygen-16-rich materials that were probably liquid droplets in the solar nebula, and oxygen isotope exchange with the surrounding oxygen-16-poor nebular gas progressed through the crystallization of the CAI. Additional oxygen isotope exchange also occurred during subsequent reheating events in the solar nebula.

Oxygen isotope exchange between refractory inclusion in allende and solar nebula Gas

PubMed

Yurimoto; Ito; Nagasawa

1998-12-04

A calcium-aluminum-rich inclusion (CAI) from the Allende meteorite was analyzed and found to contain melilite crystals with extreme oxygen-isotope compositions ( approximately 5 percent oxygen-16 enrichment relative to terrestrial oxygen-16). Some of the melilite is also anomalously enriched in oxygen-16 compared with oxygen isotopes measured in other CAIs. The oxygen isotopic variation measured among the minerals (melilite, spinel, and fassaite) indicates that crystallization of the CAI started from oxygen-16-rich materials that were probably liquid droplets in the solar nebula, and oxygen isotope exchange with the surrounding oxygen-16-poor nebular gas progressed through the crystallization of the CAI. Additional oxygen isotope exchange also occurred during subsequent reheating events in the solar nebula.

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

PubMed

Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

2015-12-01

We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Etude theorique et experimentale de la correlation entre la resistance aux chocs thermiques et aux chocs mecaniques des materiaux refractaires utilises dans les fours de traitement de l'aluminium

NASA Astrophysics Data System (ADS)

Sebbani, Mohamed Jamal Eddine

2001-07-01

This work is a theoretical and experimental study of the correlation between the resistance to thermal shock and mechanical shock of refractory materials. The study of thermal shock showed that the Bahr and Hasselman approaches are alike and that they can be combined into a single, more general approach. This generalisation allowed the division of the theoretical models into two groups: the Hasselman model and the Harmuth model. However, neither of these approaches can predict the behaviour of all refractory materials submitted to thermal shock. Therefore, the generalisation of the Hasselman approach is more appropriate for more dense materials while the Hartmuth approach is more appropriate for less dense materials. The influence of porosity on the energy of rupture helped to explain the behaviour of the less dense material. The absence of generalisation in this case allows those parameters that could be correlated with thermal shock resistance to be dependent on the type of refractory. The study of mechanical shock provided a better understanding of this mechanism. The work performed showed, theoretically and experimentally, that the resistance of the refractory materials could be correlated with the parameter s20 Egwof n-22 . This new parameter helped to explain the statistical correlation between the resistance to mechanical impact and the soxRst parameter established in earlier work. The sintering influence, which makes the refractories more resistant to this type of demand, notably by reducing the "n" coefficient, was shown. This part of the study allowed the establishment of equivalence between thermal fatigue and fatigue by mechanical impact. An evaluation of the correlation between the two mechanisms demonstrated, theoretically and experimentally, that the mechanical and thermal demands could only be exceptionally correlated. In the case of thermal shock, which are imposed deformation demands, it is the shorter cracks which are the most dangerous. However, in the case of mechanical shock, which is constraint imposed, it is the longer cracks that are the most harmful. (Abstract shortened by UMI.)

Lifetime cost of everolimus vs axitinib in patients with advanced renal cell carcinoma who failed prior sunitinib therapy in the US.

PubMed

Perrin, Allison; Sherman, Steven; Pal, Sumanta; Chua, Andrew; Gorritz, Magdaliz; Liu, Zhimei; Wang, Xufang; Culver, Kenneth; Casciano, Roman; Garrison, Louis P

2015-03-01

Everolimus and axitinib are approved in the US to treat patients with advanced renal cell carcinoma (RCC) after failure on sunitinib or sorafenib, and one prior systemic therapy (e.g., sunitinib), respectively. Two indirect comparisons performed to evaluate progression-free survival in patients treated with everolimus vs axitinib suggested similar efficacy between the two treatments. Therefore, this analysis compares the lifetime costs of these two therapies among sunitinib-refractory advanced RCC patients from a US payer perspective. A Markov model was developed to simulate a cohort of sunitinib-refractory advanced RCC patients and estimate the cost of treating patients with everolimus vs axitinib. The following health states were included: stable disease without adverse events (AEs), stable disease with AEs, disease progression (PD), and death. The model included the following resources: active treatments, post-progression treatments, adverse events, physician and nurse visits, scans and tests, and palliative care. Resource utilization inputs were derived from a US claims database analysis. Additionally, a 3% annual discount rate was applied to costs, and the robustness of the model results was tested by conducting sensitivity analyses, including those on dosing scheme and post-progression treatment costs. Base case results demonstrated that patients treated with everolimus cost an average of $12,985 (11%) less over their lifetimes than patients treated with axitinib. The primary difference in costs was related to active treatment, which was largely driven by axitinib's higher dose intensity. RESULTS remained consistent across sensitivity analyses for AE and PD treatment costs, as well as dose intensity and discount rates. The results suggest that everolimus likely leads to lower lifetime costs than axitinib for sunitinib-refractory advanced RCC patients in the US.

Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

ClinicalTrials.gov

2017-10-23

Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

Palliative management of refractory dyspnea in COPD

PubMed Central

Uronis, Hope E; Currow, David C; Abernethy, Amy P

2006-01-01

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics. PMID:18046866

Nucleation, Growth, Annealing, and Coagulation of Refractory Oxides and Metals: Recent Experimental Progress and Applications to Astrophysical Systems

NASA Technical Reports Server (NTRS)

Nuth, J. A.; Rietmeijer, F. J. M.; Hallenbeck, S. L.; Withey, P. A.

1999-01-01

Starting with cooling, refractory vapors diluted in significant quantities of H and He there are four processes that most natural systems will undergo: nucleation, growth, annealing, and coagulation. Nucleation is the processes by which the first stable refractory nuclei form in the vapor. These are the seeds onto which the remaining vapors will condense during the growth stage. Solids of any composition will try to arrange themselves into the least energetic configuration, provided that there is sufficient energy available to support such processes as diffusion and the breaking of chemical bonds. There is a significant activation energy associated with the annealing process in refractory solids due to the relatively high energy of the chemical bonds in solids. The grains formed in most cosmochemical systems are extremely small and often tightly coupled to the gas. Because of their small physical cross sections coagulation may be a very slow process unless there is another driving force involved in addition to normal Brownian motion. In what follows we will briefly cover each of these four stages for refractory oxide and metal grains, although in inverse order.

Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition.

PubMed

Blake, Zoë; Marks, Douglas K; Gartrell, Robyn D; Hart, Thomas; Horton, Patti; Cheng, Simon K; Taback, Bret; Horst, Basil A; Saenger, Yvonne M

2018-04-06

Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab. Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.

Experimental ammonia-free phosphate-bonded investments using Mg(H2PO4)2.

PubMed

Zhang, Z; Tamaki, Y; Miyazaki, T

2001-12-01

In previous study, we found that Mg(H2PO4)2 instead of NH4H2PO4 was available as a binder material for phosphate-bonded investments and possibly could be used to develop the phosphate-bonded investment without ammonia gas release. The purpose of the present study was to develop the experimental ammonia-free phosphate-bonded investments by investigating suitable refractories. Mg(H2PO4)2.nH2O and MgO were prepared as a binder. Cristobalite and quartz were selected as refractories. The power ratio of MgO/Mg(H2PO4)2.nH2O was set constant at 1.2 according to our previous findings. Fundamental properties of dental investment such as strength, manipulation and expansion were evaluated. Using cristobalite as the refractory material, further investigations were performed. The refractory/binder ratio was definitely effective. The increase of this ratio led to low mold strength and large mold expansion. The present findings suggested that C5 was desirable for dental investment.

The cathode material for a plasma-arc heater

NASA Astrophysics Data System (ADS)

Yelyutin, A. V.; Berlin, I. K.; Averyanov, V. V.; Kadyshevskii, V. S.; Savchenko, A. A.; Putintseva, R. G.

1983-11-01

The cathode of a plasma arc heater experiences a large thermal load. The temperature of its working surface, which is in contact with the plasma, reaches high values, as a result of which the electrode material is subject to erosion. Refractory metals are usually employed for the cathode material, but because of the severe erosion do not usually have a long working life. The most important electrophysical characteristic of the electrode is the electron work function. The use of materials with a low electron work function allows a decrease in the heat flow to the cathode, and this leads to an increase in its erosion resistance and working life. The electroerosion of certain materials employed for the cathode in an electric arc plasma generator in the process of reduction smelting of refractory metals was studied.

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

PubMed

Ou, Sai-Hong Ignatius; Ahn, Jin Seok; De Petris, Luigi; Govindan, Ramaswamy; Yang, James Chih-Hsin; Hughes, Brett; Lena, Hervé; Moro-Sibilot, Denis; Bearz, Alessandra; Ramirez, Santiago Viteri; Mekhail, Tarek; Spira, Alexander; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Monnet, Annabelle; Zeaiter, Ali; Kim, Dong-Wan

2016-03-01

Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases. © 2015 by American Society of Clinical Oncology.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, D.H.; Ulrich, K.H.

1998-04-21

A refractory-lined high temperature reaction vessel comprises a refractory ring lining constructed of refractory brick, a cooler, and a heat transfer medium disposed between the refractory ring lining and the cooler. The refractory brick comprises magnesia (MgO) and graphite. The heat transfer medium contacts the refractory brick and a cooling surface of the cooler, and is composed of a material that accommodates relative movement between the refractory brick and the cooler. The brick is manufactured such that the graphite has an orientation providing a high thermal conductivity in the lengthwise direction through the brick that is higher than the thermal conductivity in directions perpendicular to the lengthwise direction. The graphite preferably is flake graphite, in the range of about 10 to 20 wt %, and has a size distribution selected to provide maximum brick density. The reaction vessel may be used for performing a reaction process including the steps of forming a layer of slag on a melt in the vessel, the slag having a softening point temperature range, and forming a protective frozen layer of slag on the interior-facing surface of the refractory lining in at least a portion of a zone where the surface contacts the layer of slag, the protective frozen layer being maintained at or about the softening point of the slag. 10 figs.

Refractory lining system for high wear area of high temperature reaction vessel

DOEpatents

Hubble, D.H.; Ulrich, K.H.

1998-09-22

A refractory-lined high temperature reaction vessel comprises a refractory ring lining constructed of refractory brick, a cooler, and a heat transfer medium disposed between the refractory ring lining and the cooler. The refractory brick comprises magnesia (MgO) and graphite. The heat transfer medium contacts the refractory brick and a cooling surface of the cooler, and is composed of a material that accommodates relative movement between the refractory brick and the cooler. The brick is manufactured such that the graphite has an orientation providing a high thermal conductivity in the lengthwise direction through the brick that is higher than the thermal conductivity in directions perpendicular to the lengthwise direction. The graphite preferably is flake graphite, in the range of about 10 to 20 wt %, and has a size distribution selected to provide maximum brick density. The reaction vessel may be used for performing a reaction process including the steps of forming a layer of slag on a melt in the vessel, the slag having a softening point temperature range, and forming a protective frozen layer of slag on the interior-facing surface of the refractory lining in at least a portion of a zone where the surface contacts the layer of slag, the protective frozen layer being maintained at or about the softening point of the slag. 10 figs.

Performance Assessment of Refractory Concrete Used on the Space Shuttle's Launch Pad

NASA Technical Reports Server (NTRS)

Trejo, David; Calle, Luz Marina; Halman, Ceki

2005-01-01

The John F. Kennedy Space Center (KSC) maintains several facilities for launching space vehicles. During recent launches it has been observed that the refractory concrete materials that protect the steel-framed flame duct are breaking away from this base structure and are being projected at high velocities. There is significant concern that these projected pieces can strike the launch complex or space vehicle during the launch, jeopardizing the safety of the mission. A qualification program is in place to evaluate the performance of different refractory concretes and data from these tests have been used to assess the performance of the refractory concretes. However, there is significant variation in the test results, possibly making the existing qualification test program unreliable. This paper will evaluate data from past qualification tests, identify potential key performance indicators for the launch complex, and will recommend a new qualification test program that can be used to better qualify refractory concrete.

Synthesis of refractory materials

DOEpatents

Holt, Joseph B.

1984-01-01

Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogren. For this purpose, a metal azide is employed, preferably NaN.sub.3. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

Refractory oxide hosts for a high power, broadly tunable laser with high quantum efficiency and method of making same

DOEpatents

Chen, Yok; Gonzalez, Roberto

1986-01-01

Refractory oxide crystals having high-quantum efficiency and high thermal stability for use as broadly tunable laser host materials. The crystals are formed by removing hydrogen from a single crystal of the oxide material to a level below about 10.sup.12 protons per cm.sup.3 and subsequently thermochemically reducing the oxygen content of the crystal to form sufficient oxygen anion vacancies so that short-lived F.sup.+ luminescence is produced when the crystal is optically excited.

Refractory oxide hosts for a high power, broadly tunable laser with high quantum efficiency and method of making same

DOEpatents

Chen, Yok; Gonzalez, R.

1985-07-03

Refractory oxide crystals having high-quantum efficiency and high thermal stability for use as broadly tunable laser host materials. The crystals are formed by removing hydrogen from a single crystal of the oxide material to a level below about 10/sup 12/ protons per cm/sup 3/ and subsequently thermochemically reducing the oxygen content of the crystal to form sufficient oxygen anion vacancies so that short-lived F/sup +/ luminescence is produced when the crystal is optically excited.

Synthesis of refractory materials

DOEpatents

Holt, J.B.

1983-08-16

Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed, preferably NaN/sub 3/. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

Cometary dust: the diversity of primitive refractory grains

PubMed Central

Ishii, H. A.

2017-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive cometary particles has expanded significantly through microscale investigations of cosmic dust samples (anhydrous interplanetary dust particles (IDPs), chondritic porous (CP) IDPs and UltraCarbonaceous Antarctic micrometeorites, Stardust and Rosetta), as well as through remote sensing (Spitzer IR spectroscopy). Comet dust are aggregate particles of materials unequilibrated at submicrometre scales. We discuss the properties and processes experienced by primitive matter in comets. Primitive particles exhibit a diverse range of: structure and typology; distribution of constituents; concentration and form of carbonaceous and refractory organic matter; Mg- and Fe-contents of the silicate minerals; sulfides; existence/abundance of type II chondrule fragments; high-temperature calcium–aluminium inclusions and ameboid-olivine aggregates; and rarely occurring Mg-carbonates and magnetite, whose explanation requires aqueous alteration on parent bodies. The properties of refractory materials imply there were disc processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disc present at the time and in the region where the comets formed. This article is part of the themed issue ‘Cometary science after Rosetta’. PMID:28554979

Evolution of the Structure and Phase Composition of Deformable Refractory Nickel Alloys for GTE Discs Upon Complication of Their Alloying

NASA Astrophysics Data System (ADS)

Chabina, E. B.; Filonova, E. V.; Lomberg, B. S.; Morozova, G. I.

2015-07-01

Variation of the phase composition and structure of deformable refractory nickel alloys upon complication of their alloying is considered starting with the ÉI437B pioneer domestic alloy with heterophase hardening and ending with alloy VZh175 used as a material for advanced aircraft engines.

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

PubMed

Charles, James A; Peterlin, B L; Rapoport, Alan M; Linder, Steven L; Kabbouche, Marielle A; Sheftell, Fred D

2009-08-01

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

PubMed

Dimopoulos, Meletios A; Trotman, Judith; Tedeschi, Alessandra; Matous, Jeffrey V; Macdonald, David; Tam, Constantine; Tournilhac, Olivier; Ma, Shuo; Oriol, Albert; Heffner, Leonard T; Shustik, Chaim; García-Sanz, Ramón; Cornell, Robert F; de Larrea, Carlos Fernández; Castillo, Jorge J; Granell, Miquel; Kyrtsonis, Marie-Christine; Leblond, Veronique; Symeonidis, Argiris; Kastritis, Efstathios; Singh, Priyanka; Li, Jianling; Graef, Thorsten; Bilotti, Elizabeth; Treon, Steven; Buske, Christian

2017-02-01

In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58-74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenström Macroglobulinaemia, median number of previous therapies was four (IQR 2-6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5-18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66-94), and the estimated 18 month overall survival rate was 97% (95% CI 79-100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3-11·7) increased to 11·4 g/dL (10·9-12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8-13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenström's macroglobulinaemia. Pharmacyclics LLC, an AbbVie Company. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The last phase in the progressive neoplasic disease: care at the end-of-life, refractory symptoms and sedation].

PubMed

González Barón, Manuel; Gómez Raposo, César; Vilches Aguirre, Yolanda

2006-09-23

End-of-life is one of the most stressful phases during course of a neoplasic disease. Frequently, death of patients with cancer comes after a continuous and progressive physical impairment. As death approaches, the medical team might redefine outcomes and treat as priority symptoms and relief suffering. That care encompasses the physical, psychological, social, spiritual, and existential needs of patients and their families. However, symptoms are frequently observed that are intolerable for the patient and which do not respond to usual palliative measures. The intolerable nature and being refractory to treatment indicates to the health-care team, on many occasions, the need for sedation of the patient. The medical team can take comfort in the knowledge that they did their best to provide safe passage to all their patients and that, although they did not always cure them, the patients often were healed.

Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK).

PubMed

Heaney, Liam G; Djukanovic, Ratko; Woodcock, Ashley; Walker, Samantha; Matthews, John G; Pavord, Ian D; Bradding, Peter; Niven, Robert; Brightling, Chris E; Chaudhuri, Rekha; Arron, Joseph R; Choy, David F; Cowan, Douglas; Mansur, Adel; Menzies-Gow, Andrew; Adcock, Ian; Chung, Kian F; Corrigan, Chris; Coyle, Peter; Harrison, Timothy; Johnston, Sebastian; Howarth, Peter; Lordan, James; Sabroe, Ian; Bigler, Jeannette; Smith, Dirk; Catley, Matthew; May, Richard; Pierre, Lisa; Stevenson, Chris; Crater, Glenn; Keane, Frank; Costello, Richard W; Hudson, Val; Supple, David; Hardman, Tim

2016-02-01

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Joining of ceramics for high performance energy systems. Mid-term progress report, August 1, 1979-March 31, 1980

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

Smeltzer, C E; Metcalfe, A G

The subject program is primarily an exploratory and demonstration study of the use of silicate glass-based adhesives for bonding silicon-base refractory ceramics (SiC, Si/sub 3/N/sub 4/). The projected application is 1250 to 2050/sup 0/F relaxing joint service in high-performance energy conversion systems. The five program tasks and their current status are as follows. Task 1 - Long-Term Joint Stability. Time-temperature-transformation studies of candidate glass adhesives, out to 2000 hours simulated service exposure, are half complete. Task 2 - Environmental and Service Effects on Joint Reliability. Start up delayed due to late delivery of candidate glass fillers and ceramic specimens. Taskmore » 3 - Viscoelastic Damping of Glass Bonded Ceramics. Promising results obtained over approximately the same range of glass viscosity required for joint relaxation function (10/sup 7.5/ to 10/sup 9.5/ poise). Work is 90% complete. Task 4 - Crack Arrest and Crack Diversion by Joints. No work started due to late arrival of materials. Task 5 - Improved Joining and Fabrication Methods. Significant work has been conducted in the area of refractory pre-glazing and the application and bonding of high-density candidate glass fillers (by both hand-artisan and slip-spray techniques). Work is half complete.« less

Isotopic compositions of cometary matter returned by Stardust.

PubMed

McKeegan, Kevin D; Aléon, Jerome; Bradley, John; Brownlee, Donald; Busemann, Henner; Butterworth, Anna; Chaussidon, Marc; Fallon, Stewart; Floss, Christine; Gilmour, Jamie; Gounelle, Matthieu; Graham, Giles; Guan, Yunbin; Heck, Philipp R; Hoppe, Peter; Hutcheon, Ian D; Huth, Joachim; Ishii, Hope; Ito, Motoo; Jacobsen, Stein B; Kearsley, Anton; Leshin, Laurie A; Liu, Ming-Chang; Lyon, Ian; Marhas, Kuljeet; Marty, Bernard; Matrajt, Graciela; Meibom, Anders; Messenger, Scott; Mostefaoui, Smail; Mukhopadhyay, Sujoy; Nakamura-Messenger, Keiko; Nittler, Larry; Palma, Russ; Pepin, Robert O; Papanastassiou, Dimitri A; Robert, François; Schlutter, Dennis; Snead, Christopher J; Stadermann, Frank J; Stroud, Rhonda; Tsou, Peter; Westphal, Andrew; Young, Edward D; Ziegler, Karen; Zimmermann, Laurent; Zinner, Ernst

2006-12-15

Hydrogen, carbon, nitrogen, and oxygen isotopic compositions are heterogeneous among comet 81P/Wild 2 particle fragments; however, extreme isotopic anomalies are rare, indicating that the comet is not a pristine aggregate of presolar materials. Nonterrestrial nitrogen and neon isotope ratios suggest that indigenous organic matter and highly volatile materials were successfully collected. Except for a single (17)O-enriched circumstellar stardust grain, silicate and oxide minerals have oxygen isotopic compositions consistent with solar system origin. One refractory grain is (16)O-enriched, like refractory inclusions in meteorites, suggesting that Wild 2 contains material formed at high temperature in the inner solar system and transported to the Kuiper belt before comet accretion.

Retrospective Analysis of Nonepileptic Patients With Isolated Epileptiform Discharges Treated With Anticonvulsants.

PubMed

Swatzyna, Ronald J; Tarnow, Jay D; Proler, Meyer L; Roark, Alexandra J; MacInerney, Erin K; Kozlowski, Gerald P

2017-09-01

Many antiepileptic drugs (AEDs) have been tested on nonepileptic patients with a variety of diagnoses. The Food and Drug Administration has only approved certain AEDs for a small number of psychiatric conditions. There are few studies of nonepileptic patients that recommend an empirical trial of AEDs when isolated epileptiform discharges (IEDs) are identified in the electroencephalogram (EEG). However, no trials have been published. The purpose of this study is to evaluate the outcome of treating nonepileptic patients with AEDs when IEDs are present. Refractory cases were reviewed from a multidisciplinary practice whose EEG readings contained IEDs and were subsequently medicated with anticonvulsants by the clinic's psychiatrist. The psychiatrist's progress notes were assessed to determine the impact of adding anticonvulsants based on parent reports, teacher reports, and clinical observation. The final sample was composed of 76 refractory cases. Of the 76 patients treated with anticonvulsants, the majority were found to be improved in follow-up progress notes: 65 improved (85.53%), 6 unchanged (7.89%), and 5 more severe (6.58%). These observational findings suggest that further studies will be needed to show that IEDs may predict positive treatment outcome to anticonvulsant medication and act as a step toward an evidence-based treatment. Also, EEG screening may prove to be useful for refractory cases regardless of age, gender, or diagnosis.

Development Study of Cartridge/Crucible Tube Materials

NASA Technical Reports Server (NTRS)

McKechnie, Timothy N.; ODell, Scott J.

1998-01-01

The limitations of traditional alloys and the desire for improved performance for components is driving the increased utilization of refractory metals in tile space industry. From advanced propulsion systems to high temperature furnace components for microgravity processing, refractory metals are being used for their high melting temperatures and inherent chemical stability. Techniques have been developed to produce near net shape refractory metal components utilizing vacuum plasma spraying. Material utilization is very high, and laborious machining can be avoided. As-spray formed components have been tested and found to perform adequately. However, increased mechanical and thermal properties are needed. To improve these properties, post processing thermal treatments such as hydrogen sintering and vacuum annealing have been performed. Components formed from alloys of tungsten, rhenium, tantalum, niobium, and molybdenum are discussed and a metallurgical analyses detailing the results are presented. A qualitative comparison of mechanical properties is also included.

Evaluation of olivine refractories for TES

NASA Astrophysics Data System (ADS)

Gay, B. M.; Cochrane, R. L.; Palmour, H., III; Paisley, M. J.

1982-02-01

The principal objectives of this program are to (1) experimentally determine the degree of improvement in thermal and mechanical performance that can be obtained with an olivine thermal storage brick made of domestic materials using advanced processing techniques compared with state-of-the-art as represented by commercial European bricks, (2) conduct an assessment of existing German ceramic process technology and determine its adaptability to domestic raw materials and manufacturing practices, and (3) investigate, on a limited basis, method for further improvement of domestic-olivine brick. To date, accomplishments include (1) installation of improved, computer-based instrumentation, (2) the use of this system to determine performance characteristics of a set of heat storage refractories under cyclic use conditions, (3) acquisition of the services of a knowledgeable European consultant, (4) continued lab-scale process/property optimization studies, and (5) comparative testing of olivine-based and magnesite-based heat storage refractories in the calorimetric test facility at Purdue University.

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

PubMed Central

O'Sullivan, J M; McCready, V R; Flux, G; Norman, A R; Buffa, F M; Chittenden, S; Guy, M; Pomeroy, K; Cook, G; Gadd, J; Treleaven, J; Al-Deen, A; Horwich, A; Huddart, R A; Dearnaley, D P

2002-01-01

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. British Journal of Cancer (2002) 86, 1715–1720. doi:10.1038/sj.bjc.6600348 www.bjcancer.com © 2002 Cancer Research UK PMID:12087455

Synergistic Effect of Nitrogen and Refractory Material on TiN Formation and Equiaxed Grain Structure of Ferritic Stainless Steel

NASA Astrophysics Data System (ADS)

Lee, Mun Hyung; Park, Joo Hyun

2018-06-01

The effect of nitrogen content on the formation of an equiaxed solidification structure of Fe-16Cr steel was investigated. Moreover, two different kinds of refractory materials, i.e., alumina and magnesia, were employed to control the type of oxide inclusion. The characteristics of TiN(-oxide) inclusions were quantitatively analyzed in both molten steel and solidified samples. When the melting was carried out in the alumina refractory, the grain size continuously decreased with increasing nitrogen content. However, a minimum grain size was observed at a specific nitrogen content (approx. 150 ppm) when the steel was melted in the magnesia refractory. Most of the single TiN particles had a cuboidal shape and fine irregularly shaped particles were located along the grain boundary due to the microsegregation of Ti at the grain boundary during solidification. The type of TiN-oxide hybrid inclusion was strongly affected by the refractory material where Al2O3-TiN and MgAl2O4-TiN hybrid-type inclusions were obtained in the alumina and magnesia refractory experiments, respectively. The formation of oxide inclusions was well predicted by thermochemical computations and it was commonly found that oxide particles were initially formed, followed by the nucleation and growth of TiN. When the nitrogen content increased, the number density of TiN linearly increased in the alumina refractory experiments. However, the number of TiN exhibits a maximum at about [N] = 150 ppm, at which a minimum grain size was obtained in the magnesia refractory experiments. Therefore, the larger the number density of TiN, the smaller the primary grain size after solidification. The number density of TiN in the steel melted in the magnesia refractory was greater than that in the steel melted in the alumina refractory at given Ti and N contents, which was due to the lower planar lattice disregistry of MgAl2O4-TiN interface rather than that of Al2O3-TiN interface. When Δ T TiN (= difference between the TiN precipitation temperature and the liquidus of the steel) was 20 K to 40 K, the number density of effective TiN was maximized and thus, the grain size was minimized after solidification. Finally, although most of the TiN particles were smaller than 1 μm in the molten steel samples irrespective of the nitrogen content, TiN particles larger than 10 μm were observed in the solidified samples when the nitrogen content was greater than 150 ppm. The growth of TiN particles during melting and solidification was well predicted by the combinatorial simulation of the `Ostwald ripening model' based on the Lifshitz-Slyozov-Wagner theory in conjunction with the `Diffusion controlled model' using Ohnaka's microsegregation equation.

Synergistic Effect of Nitrogen and Refractory Material on TiN Formation and Equiaxed Grain Structure of Ferritic Stainless Steel

NASA Astrophysics Data System (ADS)

Lee, Mun Hyung; Park, Joo Hyun

2018-03-01

The effect of nitrogen content on the formation of an equiaxed solidification structure of Fe-16Cr steel was investigated. Moreover, two different kinds of refractory materials, i.e., alumina and magnesia, were employed to control the type of oxide inclusion. The characteristics of TiN(-oxide) inclusions were quantitatively analyzed in both molten steel and solidified samples. When the melting was carried out in the alumina refractory, the grain size continuously decreased with increasing nitrogen content. However, a minimum grain size was observed at a specific nitrogen content (approx. 150 ppm) when the steel was melted in the magnesia refractory. Most of the single TiN particles had a cuboidal shape and fine irregularly shaped particles were located along the grain boundary due to the microsegregation of Ti at the grain boundary during solidification. The type of TiN-oxide hybrid inclusion was strongly affected by the refractory material where Al2O3-TiN and MgAl2O4-TiN hybrid-type inclusions were obtained in the alumina and magnesia refractory experiments, respectively. The formation of oxide inclusions was well predicted by thermochemical computations and it was commonly found that oxide particles were initially formed, followed by the nucleation and growth of TiN. When the nitrogen content increased, the number density of TiN linearly increased in the alumina refractory experiments. However, the number of TiN exhibits a maximum at about [N] = 150 ppm, at which a minimum grain size was obtained in the magnesia refractory experiments. Therefore, the larger the number density of TiN, the smaller the primary grain size after solidification. The number density of TiN in the steel melted in the magnesia refractory was greater than that in the steel melted in the alumina refractory at given Ti and N contents, which was due to the lower planar lattice disregistry of MgAl2O4-TiN interface rather than that of Al2O3-TiN interface. When ΔT TiN (= difference between the TiN precipitation temperature and the liquidus of the steel) was 20 K to 40 K, the number density of effective TiN was maximized and thus, the grain size was minimized after solidification. Finally, although most of the TiN particles were smaller than 1 μm in the molten steel samples irrespective of the nitrogen content, TiN particles larger than 10 μm were observed in the solidified samples when the nitrogen content was greater than 150 ppm. The growth of TiN particles during melting and solidification was well predicted by the combinatorial simulation of the `Ostwald ripening model' based on the Lifshitz-Slyozov-Wagner theory in conjunction with the `Diffusion controlled model' using Ohnaka's microsegregation equation.

Nucleation and particle coagulation experiments in microgravity

NASA Technical Reports Server (NTRS)

Nuth, J.

1987-01-01

Measurements of the conditions under which carbon, aluminum oxide, and silicon carbide smokes condense and of the morphology and crystal structure of the resulting grains are essential if the nature of the materials ejected into the interstellar medium and the nature of the grains which eventually became part of the proto solar nebular are to be understood. Little information is currently available on the vapor-solid phase transitions of refractory metals and solids. What little experimental data do exist are, however, not in agreement with currently accepted models of the nucleation process for more volatile materials. The major obstacle to performing such experiments in earth-based laboratories is the susceptibility of these systems to convection. Evaporation of refractory materials into a low-pressure environment with a carefully controlled temperature gradient will produce refractory smokes when the critical supersaturation of the system is exceeded. Measurement of the point at which nucleation occurs, via light scattering or extinction, can not only yield nucleation data but also, information on the chemical composition and crystal structure of the condensate. Experimental requirements are presented.

Evaluations of HRI (Heat Recovery Incinerators) at NS (Naval Station) Mayport and NAS (Naval Air Station) Jacksonville, Florida-Lessons Learned Report.

DTIC Science & Technology

1984-07-01

primary chamber is lined with 2 in. of insulating mineral wool and 4 in. of castable refractory with a service temperature of 2500*F. 5.5.5.4...material. The refractory should be air cooled by circulating combustion air between it and the outer shell. A minimum of 2-in.-high density mineral wool or...passes through the roof. The 50-ft-high and 6-ft-4-in.-O.D. stack is constructed of steel and lined with 4 in. of refractory and 2 in. of mineral

Fibrous refractory composite insulation. [shielding reusable spacecraft

NASA Technical Reports Server (NTRS)

Leiser, D. B.; Goldstein, H. E.; Smith, M. (Inventor)

1979-01-01

A refractory composite insulating material was prepared from silica fibers and aluminosilicate fibers in a weight ratio ranging from 1:19 to 19:1, and about 0.5 to 30% boron oxide, based on the total fiber weight. The aluminosilicate fiber and boron oxide requirements may be satisfied by using aluminoborosilicate fibers and, in such instances, additional free boron oxide may be incorporated in the mix up to the 30% limit. Small quantities of refractory opacifiers, such as silicon carbide, may be also added. The composites just described are characterized by the absence of a nonfibrous matrix.

Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in Acute Interstitial Pneumonia.

PubMed

Gonçalves-Venade, Gabriela; Lacerda-Príncipe, Nuno; Roncon-Albuquerque, Roberto; Paiva, José Artur

2018-05-01

Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer

PubMed Central

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A.

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein—a finding that correlates with increased numbers of autophagosomes—and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of “autophagy addiction” because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer. PMID:23965851

Phase II trial of CH5424802 (alectinib hydrochloride) for recurrent or refractory ALK-positive anaplastic large cell lymphoma: study protocol for a non-randomized non-controlled trial.

PubMed

Nagai, Hirokazu; Fukano, Reiji; Sekimizu, Masahiro; Kada, Akiko; M Saito, Akiko; Asada, Ryuta; Mori, Tetsuya

2017-08-01

Currently, a standard therapy has not been established for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. While there are many treatment options, such as hematopoietic stem cell transplantation, patients with resistant disease to conventional chemotherapies have particularly poor prognosis. There is urgent need to develop new drugs because of the lack of a standard therapy and poor prognoses. This phase II trial is designed for evaluating the efficacy and safety of alectinib hydrochloride for patients with recurrent or refractory anaplastic lymphoma kinase -positive anaplastic large cell lymphoma. The primary endpoint is the response rate according to the Revised Response Criteria for Malignant Lymphoma. The secondary endpoints are pharmacokinetics, safety in children, complete response rate, response duration, progression-free survival, event-free survival, overall survival, and adverse events. The results of this trial will be the pivotal data for the drug approval of alectinib hydrochloride for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

PubMed

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

The anti-malarial chloroquine overcomes primary resistance and restores sensitivity to trastuzumab in HER2-positive breast cancer.

PubMed

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein--a finding that correlates with increased numbers of autophagosomes--and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of "autophagy addiction" because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer.

[Studying the association between genetic polymorphism of growth factors and the development of primary open-angle glaucoma].

PubMed

Kirilenko, M Yu; Tikunova, E V; Sirotina, S S; Polonikov, A V; Bushueva, O Yu; Churnosov, M I

Primary open-angle glaucoma (POAG) is a multifactorial disease, etiopathogenesis of which largely depends on growth factors. Possessing a variety of medical and biological effects, these cytokines may influence the development and progression of POAG. to reveal the role of genetic polymorphisms of growth factors in predisposition to developing POAG that is refractory to local hypotensive therapy. The object of the study were 162 patients with stage II-III POAG, in whom local hypotensive therapy was inefficient, 90 patients with stage II-III POAG well controlled on local hypotensive therapy, and 191 controls. The material for the study was venous blood taken from the cubital vein of a proband. Isolation of genomic DNA was performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of growth factors was performed through allelic discrimination. For that, synthesis of DNA was carried out via polymerase chain reaction (PCR). It is found that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is refractory to local hypotensive therapy. A statistical model for predicting such a risk has been proposed that includes: VEGF-A с.-958C>T genetic marker (rs 833,061), age, concomitant non-inflammatory ocular diseases, microvascular changes in the conjunctiva, the degree of pigmentation of the angle of the anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the model is 90.42%. The T IGFR-1 genetic variant and a combination of the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG that is refractory to local hypotensive therapy.

[Chemical and physical characteristics and toxicology of man-made mineral fibers].

PubMed

Foà, V; Basilico, S

1999-01-01

The evidence for the adverse health effects following exposure to asbestos (i.e. fibrogenic and carcinogenic effect) has prompted widespread removal of asbestos-containing materials and led to banning of asbestos internationally (in Italy, DPR 257/1992), resulting in the increased use of substitutes composed of both naturally occurring and synthetic materials, including man made mineral fibres (MMMFs) and man made organic fibres (MMOF). MMMFs represent a family of synthetic, inorganic vitreous substances derived primarily from glass, rock, slag, or clay. MMMFs are further divided into two categories: 1) man made vitreous fibres (MMVFs), further divided as follows: a) fibrous glass, including mainly continuous filament, special purpose fibres; and microfibres. The materials are typically composed of oxides of silicon, calcium, sodium, potassium, aluminum, and boron. b) Mineral wool, including glass wool, rock wool (derived from magma rock) and slag wool (made from molten slag produced in metallurgical processes such as the production of iron, steel, or copper). The main components of rock wool and slag wool are oxides of silicon, calcium, magnesium, aluminum, and iron. 2) Refractory/ceramic fibres, amorphous or partially crystalline materials made from kaolin clay or oxides of aluminum, silicon or other metal oxides (i.e. oxides of zirconium and yttrium). Less commonly, refractory fibres are also made from non-oxide refractory materials such as silicon carbide, silicon nitride, or boron nitride. Industrial production of MMVFs began in the second half of the 19th century, while ceramic fibres production began more recently, in the early 1970s. Major uses of MMMFs include thermal, acoustic and aerospace insulation, fire proofing, reinforcing material in plastics, cement and textile, optic fibres, air and liquid filtration, friction products, refractory coatings. Serious questions have been raised about health implications of MMMFs. Suspicion about the possible occurrence of adverse effects following exposure to MMMFs arises mainly from some similarities of MMMFs with asbestos (fibrous aspects, inhalability, chemical composition, free radical formation). The fibre characteristics that have been identified as crucial in influencing the pathogenesis of fibre-related adverse respiratory effects can be mainly divided into two groups: fibre dimension, and chemical composition and structure. Fibre dimension plays a determining role in conditioning penetration in the lung. In a broad sense, the term "respirable" means "capable of being carried by breath into the respiratory system". For regulatory purposes, "respirable fibres" (i.e. RFP) are defined in most countries following WHO criteria: length > 5 microns, diameter < 3 microns, length/diameter > 3. MMMFs are generally produced as fibres of diameter higher than asbestos, and too large in diameter to be respirable. Moreover, due to the production process, they are structurally amorphous. Since MMMFs have no crystalline domains, they also have no clearly defined structural faults and they fracture transversely, and randomly. Fragments that are too large to be taken up by macrophages can be resolved in the lung by a leaching--or dissolution--process which leads to a progressive reduction of particle length. In contrast, when abraded, asbestos tends to split longitudinally into new, fine, straight fibres: these fibrils are of much smaller diameter, more respirable, and consequently more hazardous than parent fibres. Fibre chemical composition plays a determining role in conditioning the higher or lower biological activity, durability, biopersistence, and biodegradability. The term "biological activity" means reactivity or ability to interact (possibly due to formation of active oxygen species, identified as a crucial step in the mechanism of action) with biological structures and tissues. Fibre "durability" is strictly related to its solubility. It can be defined as the ability to resist

Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer

ClinicalTrials.gov

2018-05-29

Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Submerged combustion melting processes for producing glass and similar materials, and systems for carrying out such processes

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

Charbonneau, Mark William

Processes of controlling submerged combustion melters, and systems for carrying out the methods. One process includes feeding vitrifiable material into a melter vessel, the melter vessel including a fluid-cooled refractory panel in its floor, ceiling, and/or sidewall, and heating the vitrifiable material with a burner directing combustion products into the melting zone under a level of the molten material in the zone. Burners impart turbulence to the molten material in the melting zone. The fluid-cooled refractory panel is cooled, forming a modified panel having a frozen or highly viscous material layer on a surface of the panel facing the moltenmore » material, and a sensor senses temperature of the modified panel using a protected thermocouple positioned in the modified panel shielded from direct contact with turbulent molten material. Processes include controlling the melter using the temperature of the modified panel. Other processes and systems are presented.« less

Method for ultra-fast boriding

DOEpatents

Erdemir, Ali; Sista, Vivekanand; Kahvecioglu, Ozgenur; Eryilmaz, Osman Levent

2017-01-31

An article of manufacture and method of forming a borided material. An electrochemical cell is used to process a substrate to deposit a plurality of borided layers on the substrate. The plurality of layers are co-deposited such that a refractory metal boride layer is disposed on a substrate and a rare earth metal boride conforming layer is disposed on the refractory metal boride layer.

Barrier Coatings for Refractory Metals and Superalloys

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

SM Sabol; BT Randall; JD Edington

2006-02-23

In the closed working fluid loop of the proposed Prometheus space nuclear power plant (SNPP), there is the potential for reaction of core and plant structural materials with gas phase impurities and gas phase transport of interstitial elements between superalloy and refractory metal alloy components during service. Primary concerns are surface oxidation, interstitial embrittlement of refractory metals and decarburization of superalloys. In parallel with kinetic investigations, this letter evaluates the ability of potential coatings to prevent or impede communication between reactor and plant components. Key coating requirements are identified and current technology coating materials are reviewed relative to these requirements.more » Candidate coatings are identified for future evaluation based on current knowledge of design parameters and anticipated environment. Coatings were identified for superalloys and refractory metals to provide diffusion barriers to interstitial transport and act as reactive barriers to potential oxidation. Due to their high stability at low oxygen potential, alumina formers are most promising for oxidation protection given the anticipated coolant gas chemistry. A sublayer of iridium is recommended to provide inherent diffusion resistance to interstitials. Based on specific base metal selection, a thin film substrate--coating interdiffusion barrier layer may be necessary to meet mission life.« less

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.

PubMed

Seymour, John F; Kipps, Thomas J; Eichhorst, Barbara; Hillmen, Peter; D'Rozario, James; Assouline, Sarit; Owen, Carolyn; Gerecitano, John; Robak, Tadeusz; De la Serna, Javier; Jaeger, Ulrich; Cartron, Guillaume; Montillo, Marco; Humerickhouse, Rod; Punnoose, Elizabeth A; Li, Yan; Boyer, Michelle; Humphrey, Kathryn; Mobasher, Mehrdad; Kater, Arnon P

2018-03-22

Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Processing and Properties Of Refractory Zirconium Diboride Composites For Use In High Temperature Applications

NASA Technical Reports Server (NTRS)

Stackpoole, Margaret; Gusman, M.; Ellerby, D.; Johnson, S. M.; Arnold, Jim (Technical Monitor)

2001-01-01

The Thermal Protection Materials and Systems Branch at NASA Ames Research Center is involved in the development of a class of refractory oxidation-resistant diboride composites termed Ultra High Temperature Ceramics or UHTCs. These composites have good high temperature properties making them candidate materials for thermal protection system (TPS) applications. The current research focuses on improving processing methods to develop more reliable composites with enhanced thermal and mechanical properties. This presentation will concentrate on the processing of ZrB2/SiC composites. Some preliminary mechanical properties and oxidation data will also be presented.

[Extracorporeal photochemotherapy in therapy-refractory subacute lupus].

PubMed

Richard, M A; Saadallah, S; Lefevre, P; Poullin, P; Buscaylet, S; Grob, J J

2002-01-01

Extracorporeal photopheresis is a leukapheresis therapy that uses psoralen and ultraviolet A irradiation. We report the case of a woman with a refractory sub acute lupus which dramatically but transitionally responded to extracorporeal photopheresis. This women, born in 1960, developed erythematous and squamous patches located on face and neckline, associated with hyperpigmented and atrophic lesions on the arms and shoulders. Investigations confirmed the diagnosis of subacute lupus without systemic disease. All lesions progressed, despite all conventional therapies leading to major aesthetic prejudice. Extracorporeal photopheresis was initiated, and after two months, all lesions, including atrophic and healing lesions had regressed, but laboratory abnormalities did not change. Extracorporeal photopheresis was well tolerated. However, treatment was discontinued nine months later, since the cutaneous lesions relapsed. Extracorporeal photopheresis could be efficient in the treatment of cutaneous autoimmune diseases through several immunomodulatory mechanisms. Extracorporeal photopheresis is a potent alternative agent in the therapy of refractory dermatological diseases

Current Standard and Investigational Approaches to the Management of Hormone-Refractory Prostate Cancer

PubMed Central

Mendiratta, Prateek; Armstrong, Andrew J; George, Daniel J

2007-01-01

Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life. PMID:17387372

Refractory rheumatoid vasculitis

PubMed Central

Kumar, Ashok; Goel, Anshul; Lapsiwala, Mehul; Singhal, Suman

2016-01-01

Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies. PMID:28031844

A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease.

PubMed

Hrdlickova, Barbara; Mulder, Chris J; Malamut, Georgia; Meresse, Bertrand; Platteel, Mathieu; Kamatani, Yoichiro; Ricaño-Ponce, Isis; van Wanrooij, Roy L J; Zorro, Maria M; Jan Bonder, Marc; Gutierrez-Achury, Javier; Cellier, Christophe; Zhernakova, Alexandra; Nijeboer, Petula; Galan, Pilar; Withoff, Sebo; Lathrop, Mark; Bouma, Gerd; Xavier, Ramnik J; Jabri, Bana; Bensussan, Nadine C; Wijmenga, Cisca; Kumar, Vinod

2018-05-21

Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5×10) were replicated in 56 independent French and Dutch patients with RCDII. After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37×10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma

PubMed Central

Jakubowiak, Andrzej J.; Benson, Don M.; Bensinger, William; Siegel, David S.D.; Zimmerman, Todd M.; Mohrbacher, Ann; Richardson, Paul G.; Afar, Daniel E.H.; Singhal, Anil K.; Anderson, Kenneth C.

2012-01-01

Purpose To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM). Patients and Methods Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m2 IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria. Results Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months. Conclusion The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM. PMID:22291084

A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement.

PubMed

Rasche, Leo; Menoret, Emmanuelle; Dubljevic, Valentina; Menu, Eline; Vanderkerken, Karin; Lapa, Constantin; Steinbrunn, Torsten; Chatterjee, Manik; Knop, Stefan; Düll, Johannes; Greenwood, Deanne L; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann; Brändlein, Stephanie

2016-09-01

Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeutic intervention. The monoclonal antibody PAT-SM6 targets surface GRP78 and leads to disease stabilization when used as single agent in a clinical trial. In this article, we evaluated expression of GRP78 in relapsed-refractory disease and explored PAT-SM6 therapy in combination regimens. GRP78 expression was immunohistochemically analyzed during disease progression and development of drug resistance throughout different stages of multiple myeloma. Activity of PAT-SM6 was evaluated in combination with anti-multiple myeloma agents lenalidomide, bortezomib, and dexamethasone in vitro Finally, we report on a multiple myeloma patient with relapsed-refractory disease treated with PAT-SM6 in combination with bortezomib and lenalidomide. Although sGRP78 expression was present at all stages, it increased with disease progression and was even strongly elevated in patients with drug-resistant and extramedullary disease. Pretreatment with dexamethasone as well as dual combination of PAT-SM6/lenalidomide further increased sGRP78 expression and consecutively showed synergistic anti-multiple myeloma effects with PAT-SM6 in proliferation assays. As proof of concept, a 62-year-old male with triple resistant multiple myeloma treated with PAT-SM6, bortezomib, and lenalidomide experienced partial remission of both intra- and extramedullary lesions. PAT-SM6 therapy in combination regimens showed efficacy in relapsed-refractory multiple myeloma. Clin Cancer Res; 22(17); 4341-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Long-Term Response and Remission with Pixantrone in Patients with Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma: Post-Hoc Analysis of the Multicenter, Open-Label, Randomized PIX301 Trial.

PubMed

Pettengell, Ruth; Coiffier, Bertrand; Egorov, Anton; Singer, Jack; Sivcheva, Lilia

2018-06-01

Pixantrone is recommended in relapsed and refractory non-Hodgkin lymphoma (NHL) or heavily pretreated NHL patients. Its conditional approval in Europe was based on results from the open-label, randomized, phase 3 PIX301 study, comparing pixantrone monotherapy with physician's choice of treatment in 140 patients with relapsed or refractory aggressive NHL. This post-hoc analysis of the PIX301 study investigated possible correlations between patient characteristics and clinical response in 17 patients (24%) treated with pixantrone who achieved a complete response (CR) or an unconfirmed complete response (CRu) at study end. These patients (10 male and 7 female) had a median age of 61 (range 41-75) years, and the most common diagnoses were diffuse large B-cell lymphoma (n = 10) and transformed indolent lymphoma (n = 4). Most had received two prior lines of therapy (n = 12). There was wide variation in the time from diagnosis to study entry (219-4777 days). Among the 17 patients who achieved a CR/CRu with pixantrone, 6 had stable or progressive disease as a response to their last regimen, 7 had a partial response, and 4 had a CR/CRu. Four patients from the pixantrone group survived without progression for more than 400 days. Prior response to previous therapies did not appear to affect long-term response to pixantrone. These observations suggest that pixantrone monotherapy in patients with multiply relapsed or refractory aggressive NHL who had received at least two prior therapies can be associated with durable responses and long-term remission, and this may be unrelated to the clinical response to the last therapy.

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

PubMed

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

PubMed

Lee, Chung-Shien; Rattu, Mohammad A; Kim, Sara S

2016-02-01

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies. © The Author(s) 2014.

Refractory materials in comet samples

NASA Astrophysics Data System (ADS)

Joswiak, D. J.; Brownlee, D. E.; Nguyen, A. N.; Messenger, S.

2017-08-01

Transmission electron microscope examination of more than 250 fragments, >1 μm from comet Wild 2 and a giant cluster interplanetary dust particle (GCP) of probable cometary origin has revealed four new calcium-aluminum-rich inclusions (CAIs), an amoeboid olivine aggregate (AOA), and an additional AOA or Al-rich chondrule (ARC) object. All of the CAIs have concentric mineral structures and are composed of spinel + anorthite cores surrounded by Al,Ti clinopyroxenes and are similar to two previous CAIs discovered in Wild 2. All of the cometary refractory objects are of moderate refractory character. The mineral assemblages, textures, and bulk compositions of the comet CAIs are similar to nodules in fine-grained, spinel-rich inclusions (FGIs) found in primitive chondrites and like the nodules may be nebular condensates that were altered via solid-gas reactions in the solar nebula. Oxygen isotopes collected on one Wild 2 CAI also match FGIs. The lack of the most refractory inclusions in the comet samples may reflect the higher abundances of small moderately refractory CAI nodules that were produced in the nebula and the small sample sizes collected. In the comet samples, approximately 2-3% of all fragments larger than 1 μm, by number, are CAIs and nearly 50% of all bulbous Stardust tracks contain at least one CAI. We estimate that 0.5 volume % of Wild 2 material and 1 volume % of GCP is in the form of CAIs. ARCs and AOAs account for <1% of the Wild 2 and GCP grains by number.

Layer Structure of a Refractory Multilayer Ti/Al Composite After Pressure Diffusion Welding

NASA Astrophysics Data System (ADS)

Karpov, M. I.; Korzhov, V. P.; Zheltyakova, I. S.

2016-05-01

A composite refractory material with layer structure obtained by the method of pressure diffusion welding of multilayer Ti/Al packets composed of Ti- and Al-foils is studied. The welding temperature of the packets does not exceed 1200 - 1250°C. A layer structure forms in the process of interdiffusion of titanium and aluminum during welding of the packets.

Disk filter

DOEpatents

Bergman, Werner

1986-01-01

An electric disk filter provides a high efficiency at high temperature. A hollow outer filter of fibrous stainless steel forms the ground electrode. A refractory filter material is placed between the outer electrode and the inner electrically isolated high voltage electrode. Air flows through the outer filter surfaces through the electrified refractory filter media and between the high voltage electrodes and is removed from a space in the high voltage electrode.

Disk filter

DOEpatents

Bergman, W.

1985-01-09

An electric disk filter provides a high efficiency at high temperature. A hollow outer filter of fibrous stainless steel forms the ground electrode. A refractory filter material is placed between the outer electrode and the inner electrically isolated high voltage electrode. Air flows through the outer filter surfaces through the electrified refractory filter media and between the high voltage electrodes and is removed from a space in the high voltage electrode.

Effects of Different Calcium Compounds on the Corrosion Resistance of Andalusite-Based Low-Cement Castables in Contact with Molten Al-Alloy

NASA Astrophysics Data System (ADS)

Adabifiroozjaei, Esmaeil; Saidi, Ali; Monshi, Ahmad; Koshy, Pramod

2011-04-01

Andalusite containing low-cement castables (LCCs) have been used in aluminum casthouses for several decades. CaF2 is commonly added to the refractory to improve its corrosion resistance mainly because of its role in the formation of anorthite (CaAl2Si2O8); the latter has been reported to decrease the penetration of molten aluminum alloys into refractories. This article investigates the effect of the addition of different calcium containing compounds (CaO, CaCO3, CaSO4, CaF2, Clinker white cement, calcia feldspar, wollastonite, and Ca3(PO4)2) on reactions with the refractory constituents to form anorthite as well as the effect of the additives on both the subsequent physical properties and the corrosion resistance of andalusite LCC refractories. Corrosion tests using the Alcoa cup test at temperatures (1123 K [850 °C] for 150 hours and 1433 K [1160 °C] for 72 hours) were conducted to determine the extent of penetration, whereas immersion tests in boiling water were conducted to determine the extent of open porosity in the material. Scanning electron microscopy coupled with energy dispersive spectrometer, optical microscopy, and X-ray diffraction techniques were employed to characterize the phase formations in the materials after the tests. The study demonstrated that both calcia feldspar and clinker white cement had the potential to be used as new additives for decreasing the penetration of molten Al-alloy into the refractory materials. Anorthite formation (in the refractory matrix), along with the absence of glassy phases, were responsible for the improvement in the corrosion resistance of the castables containing calcia feldspar. However, in the sample containing cement, the presence of calcium silicate phases were observed to resist reactions with molten aluminum. The observed results were validated using thermodynamic calculations, which indicated that tricalcium silicates (3CaO.SiO2) and dicalcium silicate (2CaO.SiO2) phases were more resistant than wollastonite (CaSiO3) for applications involving contact with molten aluminum.

Replacing critical and strategic refractory metal elements in nickel-base superalloys. [NASA's COSAM program

NASA Technical Reports Server (NTRS)

Stephens, J. R.; Dreshfield, R. L.; Nathal, M. V.

1983-01-01

Because of the import status and essential nature of their use, cobalt, chromium, tantalum, and niobium were identified as strategic and critical in the aerospace industry. NASA's Conservation of Strategic Aerospace Materials (COSAM) program aims to reduce the need for strategic materials used in gas turbine engines. Technological thrusts in two major areas are under way to meet the primary objective of conserving the use of strategic materials in nickelbase superalloys. These thrusts consist of strategic element substitution and alternative material identification. The program emphasizes cooperative research teams involving NASA Lewis Research Center, universities, and industry. The adoption of refractory metals in nickel-base superalloys is summarized including their roles in mechanical strengthening and environmental resistance; current research activities under way in the COSAM Program are presented as well as research findings to date.

Alloy design for intrinsically ductile refractory high-entropy alloys

NASA Astrophysics Data System (ADS)

Sheikh, Saad; Shafeie, Samrand; Hu, Qiang; Ahlström, Johan; Persson, Christer; Veselý, Jaroslav; Zýka, Jiří; Klement, Uta; Guo, Sheng

2016-10-01

Refractory high-entropy alloys (RHEAs), comprising group IV (Ti, Zr, Hf), V (V, Nb, Ta), and VI (Cr, Mo, W) refractory elements, can be potentially new generation high-temperature materials. However, most existing RHEAs lack room-temperature ductility, similar to conventional refractory metals and alloys. Here, we propose an alloy design strategy to intrinsically ductilize RHEAs based on the electron theory and more specifically to decrease the number of valence electrons through controlled alloying. A new ductile RHEA, Hf0.5Nb0.5Ta0.5Ti1.5Zr, was developed as a proof of concept, with a fracture stress of close to 1 GPa and an elongation of near 20%. The findings here will shed light on the development of ductile RHEAs for ultrahigh-temperature applications in aerospace and power-generation industries.

PROCESS OF PRODUCING REFRACTORY URANIUM OXIDE ARTICLES

DOEpatents

Hamilton, N.E.

1957-12-01

A method is presented for fabricating uranium oxide into a shaped refractory article by introducing a uranium halide fluxing reagent into the uranium oxide, and then mixing and compressing the materials into a shaped composite mass. The shaped mass of uranium oxide and uranium halide is then fired at an elevated temperature so as to form a refractory sintered article. It was found in the present invention that the introduction of a uraninm halide fluxing agent afforded a fluxing action with the uranium oxide particles and that excellent cohesion between these oxide particles was obtained. Approximately 90% of uranium dioxide and 10% of uranium tetrafluoride represent a preferred composition.

Refractory metal particles in refractory inclusions in the Allende meteorite

NASA Technical Reports Server (NTRS)

Fuchs, L. H.; Blander, M.

1980-01-01

SEM and X-ray analysis were used to study refractory metal particles in five calcium-aluminum-rich inclusions in the Allende meteorite, and a complex variety of compositions and large departures from equilibrium were found. It is suggested that these particles could have been primordial condensates which were isolated from the nebula and from each other at different times by cocondensing oxides. Selective diffusion and/or oxidation of the more oxidizable metals (Mo, W, Fe, and Ni), phase segregations into different alloy phases (fcc, bcc, hcp, and, possibly, ordered phases), and the formation of metastable condensates could have been involved in the genesis of these materials

Mechanical Properties of Low-Density, Refractory Multi-Principal Element Alloys of the Cr-Nb-Ti-V-Zr System (Postprint)

DTIC Science & Technology

2014-04-01

PROPERTIES OF LOW-DENSITY, REFRACTORY MULTI-PRINCIPAL ELEMENT ALLOYS OF THE Cr– Nb –Ti–V– Zr SYSTEM (POSTPRINT) 5a. CONTRACT NUMBER In-house 5b...element alloys of the Cr– Nb –Ti–V– Zr systemO.N. Senkov n, S.V. Senkova, D.B. Miracle, C. Woodward Air Force Research Laboratory, Materials and...densities below 7.0 g/cm3 have recently been produced by alloying Nb (rNb¼8.57 g/cm3) with four low density refractory elements, V (rV¼6.11 g/cm3), Zr

Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

PubMed

Villablanca, Judith G; Ji, Lingyun; Shapira-Lewinson, Adi; Marachelian, Araz; Shimada, Hiroyuki; Hawkins, Randall A; Pampaloni, Miguel; Lai, Hollie; Goodarzian, Fariba; Sposto, Richard; Park, Julie R; Matthay, Katherine K

2018-05-01

The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing. © 2018 Wiley Periodicals, Inc.

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

PubMed

Cooray, Shamil D; Topliss, Duncan J

2017-01-01

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and timely intervention are required for TKI-related adverse effects.There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors.

PubMed

Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus M; Hari, Parameswaran N; Ahn, Kwang Woo; Carreras, Jeanette; Bachanova, Veronika; Bashey, Asad; Cohen, Jonathon B; D'Souza, Anita; Freytes, César O; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark S; Holmberg, Leona A; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Ku, Grace H; Laport, Ginna G; Lazarus, Hillard M; Miller, Alan M; Mussetti, Alberto; Olsson, Richard F; Slavin, Shimon; Usmani, Saad Z; Vij, Ravi; Wood, William A; Maloney, David G; Sureda, Anna M; Smith, Sonali M; Hamadani, Mehdi

2015-12-01

This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P < .0001); relapse/progression: 54% versus 20% (P < .0001); progression-free survival (PFS): 41% versus 58% (P < .001), and overall survival (OS): 74% versus 66% (P = .05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P < .0001) and worse PFS (RR, 2.9; P < .0001) beyond 11 months after HCT. In the first 24 months after HCT, auto-HCT was associated with improved OS (RR, .41; P < .0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P = .006). A landmark analysis of patients alive and progression-free at 2 years after HCT confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P < .0001) and inferior PFS (RR, 3.2; P < .0001) and OS (RR, 2.1; P = .04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity-conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Ulcerative proctitis: an update on the pharmacotherapy and management.

PubMed

Gecse, Krisztina B; Lakatos, Peter L

2014-08-01

Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.

The natural history of skin-limited Langerhans cell histiocytosis: a single-institution experience.

PubMed

Ehrhardt, Matthew J; Humphrey, Stephen R; Kelly, Michael E; Chiu, Yvonne E; Galbraith, Sheila S

2014-11-01

Prior reports of Langerhans cell histiocytosis (LCH) suggest that isolated skin involvement is rare and often progresses to systemic disease. More rapid access to pediatric subspecialty care has likely led to more frequent representation of this condition. The purpose of this study is to characterize the natural history of skin-limited LCH in an era of increased access to pediatric subspecialty care. A retrospective chart review was performed on all patients newly diagnosed with LCH between 2001 and 2012 at the Children's Hospital of Wisconsin. Extensive review of laboratory, physical examination, and imaging reports was performed and data collected for patients with biopsy-proven skin LCH. Sixteen individuals with skin-limited LCH were identified. The median age at onset of skin eruption was birth (range, birth to 6 mo), and median duration of follow-up was 19.5 months (range, 2 wk to 10 y) from diagnosis. One patient (6%) developed pituitary disease and 1 patient (6%) had refractory skin involvement. All others experienced complete resolution. For patients without progressive or refractory disease, resolution of skin findings occurred within 7 months from onset. Progression of skin-limited to multisystem LCH likely may be less frequent than previously described.

Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decreases chromogranin a in patients with androgen ablation refractory prostate cancer.

PubMed

Di Silverio, Franco; Sciarra, Alessandro

2003-11-01

We evaluated whether a combination therapy of ethinylestradiol and somatostatin analogue can reintroduce objective clinical responses in patients with metastatic androgen ablation refractory prostate cancer (PC). Ten patients with stage D3 disease and bone metastases who had progression despite initial responses to combined androgen blockade and in whom antiandrogen withdrawal subsequently failed discontinued combined androgen blockade and received 1 mg ethinylestradiol orally daily and 73.9 mg lanreotide acetate intramuscularly every 4 weeks. Serum prostate specific antigen (PSA), chromogranin A (CgA), Eastern Cooperative Oncology Group performance status and bone pain scores were assessed at regular intervals. Median followup was 18 months (range 10 to 24). Nine of the 10 cases (90%, 95% CI 55.5 to 99.8) had an objective clinical response, defined as a greater than 50% PSA decrease (median 87.1%, range 50.2% to 94.4%). PSA normalization (less than 4 ng/ml) was achieved in 3 cases. All patients reported significant and durable improvement in bone pain (median duration 17.5 months) and performance status (median duration 18 months) without major treatment related side effects. Two patients with disease progression died secondary to PC at 16 and 10 months, respectively. All other patients were without progression. We observed a statistically significant decrease in serum CgA during administration and at the response to therapy (median 38.4%, range 28.6% to 64.9%, (p <0.0001). Interestingly CgA was not increased at relapse. This combination therapy seems to reintroduce an objective clinical response and symptomatic improvement in androgen ablation refractory PC cases.

Improved Rare-Earth Emitter Hollow Cathode

NASA Technical Reports Server (NTRS)

Goebel, Dan M.

2011-01-01

An improvement has been made to the design of the hollow cathode geometry that was created for the rare-earth electron emitter described in Compact Rare Earth Emitter Hollow Cathode (NPO-44923), NASA Tech Briefs, Vol. 34, No. 3 (March 2010), p. 52. The original interior assembly was made entirely of graphite in order to be compatible with the LaB6 material, which cannot be touched by metals during operation due to boron diffusion causing embrittlement issues in high-temperature refractory materials. Also, the graphite tube was difficult to machine and was subject to vibration-induced fracturing. This innovation replaces the graphite tube with one made out of refractory metal that is relatively easy to manufacture. The cathode support tube is made of molybdenum or molybdenum-rhenium. This material is easily gun-bored to near the tolerances required, and finish machined with steps at each end that capture the orifice plate and the mounting flange. This provides the manufacturability and robustness needed for flight applications, and eliminates the need for expensive e-beam welding used in prior cathodes. The LaB6 insert is protected from direct contact with the refractory metal tube by thin, graphite sleeves in a cup-arrangement around the ends of the insert. The sleeves, insert, and orifice plate are held in place by a ceramic spacer and tungsten spring inserted inside the tube. To heat the cathode, an insulating tube is slipped around the refractory metal hollow tube, which can be made of high-temperature materials like boron nitride or aluminum nitride. A screw-shaped slot, or series of slots, is machined in the outside of the ceramic tube to constrain a refractory metal wire wound inside the slot that is used as the heater. The screw slot can hold a single heater wire that is then connected to the front of the cathode tube by tack-welding to complete the electrical circuit, or it can be a double slot that takes a bifilar wound heater with both leads coming out the back. This configuration replaces the previous sheathed heater design that limited the cycling-life of the cathode.

Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.

PubMed

Fan, Hui; Lu, Xuechun; Wang, Xiaohui; Liu, Yang; Guo, Bo; Zhang, Yan; Zhang, Wenying; Nie, Jing; Feng, Kaichao; Chen, Meixia; Zhang, Yajing; Wang, Yao; Shi, Fengxia; Fu, Xiaobing; Zhu, Hongli; Han, Weidong

2014-01-01

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

Protective sheath for a continuous measurement thermocouple

DOEpatents

Phillippi, R.M.

1991-12-03

Disclosed is a protective thermocouple sheath of a magnesia graphite refractory material for use in continuous temperature measurements of molten metal in a metallurgical ladle and having a basic slag layer thereon. The sheath includes an elongated torpedo-shaped sheath body formed of a refractory composition and having an interior borehole extending axially therethrough and adapted to receive a thermocouple. The sheath body includes a lower end which is closed about the borehole and forms a narrow, tapered tip. The sheath body also includes a first body portion integral with the tapered tip and having a relatively constant cross section and providing a thin wall around the borehole. The sheath body also includes a second body portion having a relatively constant cross section larger than the cross section of the first body portion and providing a thicker wall around the borehole. The borehole terminates in an open end at the second body portion. The tapered tip is adapted to penetrate the slag layer and the thicker second body portion and its magnesia constituent material are adapted to withstand chemical attack thereon from the slag layer. The graphite constituent improves thermal conductivity of the refractory material and, thus, enhances the thermal responsiveness of the device. 4 figures.

Protective sheath for a continuous measurement thermocouple

DOEpatents

Phillippi, R. Michael

1991-01-01

Disclosed is a protective thermocouple sheath of a magnesia graphite refractory material for use in continuous temperature measurements of molten metal in a metallurgical ladle and having a basic slag layer thereon. The sheath includes an elongated torpedo-shaped sheath body formed of a refractory composition and having an interior borehole extending axially therethrough and adapted to receive a thermocouple. The sheath body includes a lower end which is closed about the borehole and forms a narrow, tapered tip. The sheath body also includes a first body portion integral with the tapered tip and having a relatively constant cross section and providing a thin wall around the borehole. The sheath body also includes a second body portion having a relatively constant cross section larger than the cross section of the first body portion and providing a thicker wall around the borehole. The borehole terminates in an open end at the second body portion. The tapered tip is adapted to penetrate the slag layer and the thicker second body portion and its magnesia constituent material are adapted to withstand chemical attack thereon from the slag layer. The graphite constituent improves thermal conductivity of the refractory material and, thus, enhances the thermal responsiveness of the device.

Refractory Gastrointestinal Bleeding: Role of Angiographic Intervention

PubMed Central

2013-01-01

Although endoscopic hemostasis remains initial treatment modality for nonvariceal gastrointestinal (GI) bleeding, severe bleeding despite endoscopic management occurs in 5% to 10% of the patients, requiring surgery or transcatheter arterial embolization (TAE). TAE is now considered the first-line therapy for massive GI bleeding refractory to endoscopic management. GI endoscopists need to be familiar with indications, principles, outcomes, and complications of TAE, as well as embolic materials available. PMID:24143308

Compatibility of Niobium Alloys and Superalloys in a Flowing He-Xe Power Conversion System

NASA Technical Reports Server (NTRS)

Bowman, Cheryl L.; Ritzert, Frank J.; Smialek, James L.; Jaster, Mark L.; rker, Samuel P.

2004-01-01

Proposed concepts for an ambitious mission to explore Jupiter's three icy moons place significant demands on the various spacecraft systems. There are many challenges related to the high output power conversion systems being considered, and one example is the need to ensure system compatibility at all levels. The utilization of appropriate materials for component structures is important to ensuring long mission life. Refractory metal alloys have attractive high-temperature properties in inert environments, but these alloys are sometimes susceptible to contamination. Potential material compatibility issues exist between refractory metal candidates and more conventional alloys. Nb-1Zr has long been considered one of the most well characterized refractory alloys that is well suited for elevated-temperature use and liquid-metal compatibility. However, previous studies have suggested that niobium alloys can not co-exist in a closed system with traditional stainless steels or superalloys due to transport of contaminants. The relevance of this information to a proposed power conversion system is discussed. Also, experiments and fundamental calculations are being performed to determine contamination transport from candidate superalloys to Nb-1Zr in a closed system with an inert carrier gas. Potential protective schemes are explored to ensure system level compatibility between the refractory alloy Nb-1Zr and a nickel-based superalloy.

Refractory clad transient internal probe for magnetic field measurements in high temperature plasmas

NASA Astrophysics Data System (ADS)

Kim, Hyundae; Cellamare, Vincent; Jarboe, Thomas R.; Mattick, Arthur T.

2005-05-01

The transient internal probe (TIP) is a diagnostic for local internal field measurements in high temperature plasmas. A verdet material, which rotates the polarization angle of the laser light under magnetic fields, is launched into a plasma at about 1.8km/s. A linearly polarized Ar+ laser illuminates the probe in transit and the light retroreflected from the probe is analyzed to determine the local magnetic field profiles. The TIP has been used for magnetic field measurements on the helicity injected torus where electron temperature Te⩽80eV. In order to apply the TIP in higher temperature plasmas, refractory clad probes have been developed utilizing a sapphire tube, rear disc, and a MgO window on the front. The high melting points of these refractory materials should allow probe operation at plasma electron temperatures up to Te˜300eV. A retroreflecting probe has also been developed using "catseye" optics. The front window is replaced with a plano-convex MgO lens, and the back surface of the probe is aluminized. This approach reduces spurious polarization effects and provides refractory cladding for the probe entrance face. In-flight measurements of a static magnetic field demonstrate the ability of the clad probes to withstand gun-launch acceleration, and provide high accuracy measurements of magnetic field.

Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

PubMed

Lu, Chien-Hsing; Chang, Yen-Hou; Lee, Wai-Hou; Chang, Yi; Peng, Chia-Wen; Chuang, Chi-Mu

2016-01-01

The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p < 0.001, for platinum-refractory/resistant disease, and 9.8 vs. 6.9 months, p < 0.001, for platinum-sensitive disease). Second-line IP chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy. © 2016 S. Karger AG, Basel.

Progress in bioleaching: part B: applications of microbial processes by the minerals industries.

PubMed

Brierley, Corale L; Brierley, James A

2013-09-01

This review presents developments and applications in bioleaching and mineral biooxidation since publication of a previous mini review in 2003 (Olson et al. Appl Microbiol Biotechnol 63:249-257, 2003). There have been discoveries of newly identified acidophilic microorganisms that have unique characteristics for effective bioleaching of sulfidic ores and concentrates. Progress has been made in understanding and developing bioleaching of copper from primary copper sulfide minerals, chalcopyrite, covellite, and enargite. These developments point to low oxidation-reduction potential in concert with thermophilic bacteria and archaea as a potential key to the leaching of these minerals. On the commercial front, heap bioleaching of nickel has been commissioned, and the mineral biooxidation pretreatment of sulfidic-refractory gold concentrates is increasingly used on a global scale to enhance precious metal recovery. New and larger stirred-tank reactors have been constructed since the 2003 review article. One biooxidation-heap process for pretreatment of sulfidic-refractory gold ores was also commercialized. A novel reductive approach to bioleaching nickel laterite minerals has been proposed.

Submicron particle mass concentrations and sources in the Amazonian wet season (AMAZE-08)

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

Chen, Q.; Farmer, D. K.; Rizzo, L. V.

Real-time mass spectra of non-refractory component of submicron aerosol particles were recorded in a tropical rainforest in the central Amazon basin during the wet season of 2008, as a part of the Amazonian Aerosol Characterization Experiment (AMAZE-08). Organic components accounted on average for more than 80% of the non-refractory submicron particle mass concentrations during the period of measurements. Ammonium was present in sufficient quantities to halfway neutralize sulfate. In this acidic, isoprene-dominated, low-NOx environment the high-resolution mass spectra as well as mass closures with ion chromatography measurements did not provide evidence for significant contributions of organosulfate species, at least atmore » concentrations above uncertainty levels. Positive-matrix factorization of the time series of particle mass spectra identified four statistical factors to account for the variance of the signal intensities of the organic constituents: a factor HOA having a hydrocarbon-like signature and identified as regional emissions of primary organic material, a factor OOA-1 associated with fresh production of secondary organic material by a mechanism of BVOC oxidation followed by gas-to-particle conversion, a factor OOA-2 consistent with reactive uptake of isoprene oxidation products, especially epoxydiols by acidic particles, and a factor OOA-3 associated with long range transport and atmospheric aging. The OOA-1, -2, and -3 factors had progressively more oxidized signatures. Diameter-resolved mass spectral markers also suggested enhanced reactive uptake of isoprene oxidation products to the accumulation mode for the OOA-2 factor, and such size partitioning can be indicative of in-cloud process. The campaign-average factor loadings were in a ratio of 1.1:1.0 for the OOA-1 compared to the OOA-2 pathway, suggesting the comparable importance of gas-phase compared to particle-phase (including cloud waters) production pathways of secondary organic material during the study period.« less

Effect of Different Structural Materials on Neutronic Performance of a Hybrid Reactor

NASA Astrophysics Data System (ADS)

Übeyli, Mustafa; Tel, Eyyüp

2003-06-01

Selection of structural material for a fusion-fission (hybrid) reactor is very important by taking into account of neutronic performance of the blanket. Refractory metals and alloys have much higher operating temperatures and neutron wall load (NWL) capabilities than low activation materials (ferritic/martensitic steels, vanadium alloys and SiC/SiC composites) and austenitic stainless steels. In this study, effect of primary candidate refractory alloys, namely, W-5Re, T111, TZM and Nb-1Zr on neutronic performance of the hybrid reactor was investigated. Neutron transport calculations were conducted with the help of SCALE 4.3 System by solving the Boltzmann transport equation with code XSDRNPM. Among the investigated structural materials, tantalum had the worst performance due to the fact that it has higher neutron absorption cross section than others. And W-5Re and TZM having similar results showed the best performance.

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.

PubMed

Jones, Jeffrey A; Mato, Anthony R; Wierda, William G; Davids, Matthew S; Choi, Michael; Cheson, Bruce D; Furman, Richard R; Lamanna, Nicole; Barr, Paul M; Zhou, Lang; Chyla, Brenda; Salem, Ahmed Hamed; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Coutre, Steven; Woyach, Jennifer; Byrd, John C

2018-01-01

Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy. In this interim analysis of a multicentre, open-label, non-randomised, phase 2 trial, we enrolled patients aged 18 years or older with a documented diagnosis of chronic lymphocytic leukaemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance score of 2 or lower. All patients had relapsed or refractory disease after previous treatment with a BCR signalling pathway inhibitor. All patients were screened for Richter's transformation and cases confirmed by biopsy were excluded. Eligible patients received oral venetoclax, starting at 20 mg per day with stepwise dose ramp-up over 5 weeks to 400 mg per day. Patients with rapidly progressing disease received an accelerated dosing schedule (to 400 mg per day by week 3). The primary endpoint was overall response, defined as the proportion of patients with an overall response per investigator's assessment according to IWCLL criteria. All patients who received at least one dose of venetoclax were included in the activity and safety analyses. This study is ongoing; data for this interim analysis were collected per regulatory agencies' request as of June 30, 2017. This trial is registered with ClinicalTrials.gov, number NCT02141282. Between September, 2014, and November, 2016, 127 previously treated patients with relapsed or refractory chronic lymphocytic leukaemia were enrolled from 15 sites across the USA. 91 patients had received ibrutinib as the last BCR inhibitor therapy before enrolment, 43 of whom were enrolled in the main cohort and 48 in the expansion cohort recruited later after a protocol amendment. At the time of analysis, the median follow-up was 14 months (IQR 8-18) for all 91 patients, 19 months (9-27) for the main cohort, and 12 months (8-15) for the expansion cohort. 59 (65%, 95% CI 53-74) of 91 patients had an overall response, including 30 (70%, 54-83) of 43 patients in the main cohort and 29 (60%, 43-72) of 48 patients in the expansion cohort. The most common treatment-emergent grade 3 or 4 adverse events were neutropenia (46 [51%] of 91 patients), thrombocytopenia (26 [29%]), anaemia (26 [29%]), decreased white blood cell count (17 [19%]), and decreased lymphocyte count (14 [15%]). 17 (19%) of 91 patients died, including seven because of disease progression. No treatment-related deaths occurred. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukaemia whose disease progressed during or after discontinutation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019. AbbVie, Genentech. Copyright © 2018 Elsevier Ltd. All rights reserved.

NBS: Materials measurements

NASA Technical Reports Server (NTRS)

Manning, J. R.

1981-01-01

Measurement of materials properties and thermophysical properties is described. The topics discussed are: surface tensions and their variations with temperature and impurities; convection during unidirectional solidification: measurement of high temperature thermophysical properties of tungsten liquid and solid; thermodynamic properties of refractory materials at high temperatures; and experimental and theoretical studies in wetting and multilayer adsorption.

Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma

ClinicalTrials.gov

2015-08-18

Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma

High Temperature Stability of Dissimilar Metal Joints in Fission Surface Power Systems

NASA Technical Reports Server (NTRS)

Locci, Ivan E.; Nesbitt, James A.; Ritzert, Frank J.; Bowman, Cheryl L.

2007-01-01

Future generations of power systems for spacecraft and lunar surface systems will likely require a strong dependence on nuclear power. The design of a space nuclear power plant involves integrating together major subsystems with varying materia1 requirements. Refractory alloys are repeatedly considered for major structural components in space power reactor designs because refractory alloys retain their strength at higher temperatures than other classes of metals. The relatively higher mass and lower ductility of the refractory alloys make them less attractive for lower temperature subsystems in the power plant such as the power conversion system. The power conversion system would consist more likely of intermediate temperature Ni-based superalloys. One of many unanswered questions about the use of refractory alloys in a space power plant is how to transition from the use of the structural refractory alloy to more traditional structural alloys. Because deleterious phases can form when complex alloys are joined and operated at elevated temperatures, dissimilar material diffusion analyses of refractory alloys and superalloys are needed to inform designers about options of joint temperature and operational lifetime. Combinations of four superalloys and six refractory alloys were bonded and annealed at 1150 K and 1300 K to examine diffusional interactions in this study. Joints formed through hot pressing and hot isostatic pressing were compared. Results on newer alloys compared favorably to historical data. Diffusional stability is promising for some combinations of Mo-Re alloys and superalloys at 1150 K, but it appears that lower joint temperatures would be required for other refractory alloy couples.

Atomic Oxygen Exposure of Power System and other Spacecraft Materials: Results of the EOIM-3 Experiment

NASA Technical Reports Server (NTRS)

Morton, Thomas L.; Ferguson, Dale C.

1997-01-01

In order to test their reactivity with Atomic Oxygen, twenty five materials were flown on the EOIM-3 (Evaluation of Oxygen Interactions with Materials) portion of the STS-46 Mission. These materials include refractory metals, candidate insulation materials, candidate radiator coatings, and a selection of miscellaneous materials. This report documents the results of the pre- and post-flight analysis of these materials.

Management of refractory pityriasis rubra pilaris: challenges and solutions

PubMed Central

Moretta, Gaia; De Luca, Erika V; Di Stefani, Alessandro

2017-01-01

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous skin disease. Its clinical presentation and evolution is very variable. The most frequent clinical features are follicular papules, progressing to yellow-orange erythroderma with round small areas of normal skin and the well-demarcated palmoplantar keratoderma. Actually, six different types of PRP have been described based on clinical characteristics, age of onset, and prognosis. The pathogenesis is still unknown, and treatment can be challenging. Available treatments are mainly based on case reports or case series of clinical experience because no controlled randomized trials have never been performed because of the rarity of the condition. Traditional systemic treatment consists in retinoids, which are actually considered as first-line therapy, but refractory cases that do not respond or relapse after drug interruption do exist. In recent years, numerous reports have demonstrated the efficacy of new agents such as biological drugs. This article is an overview on available therapeutic options, in particular for refractory forms of PRP. PMID:29184428

Chlorination processing of local planetary ores for oxygen and metallurgically important metals

NASA Technical Reports Server (NTRS)

Lynch, D. C.

1989-01-01

The use of chlorine to extract, reclaim, and purify metals has attractive possibilities for extraterrestrial processing of local planetary resources. While a complete cyclic process has been proposed for the recovery of metallurgically significant metals and oxygen, herein the chlorination step of the cycle is examined. An experimental apparatus for reacting refractory materials, such as ilmenite, in a microwave induced plasma is being built. Complex equilibria calculations reveal that stable refractory materials can, under the influence of a plasma, undergo chlorination and yield oxygen as a by-product. These issues and the potential advantages for plasma processing in space are reviewed. Also presented is a discussion of the complex equilibria program used in the analysis.

Advanced composite alloys for constructional parts of robots

NASA Astrophysics Data System (ADS)

Issin, D. K.; Zholdubayeva, Zh D.; Neshina, Y. G.; Alkina, A. D.; Khuangan, N.; Rahimova, G. M.

2018-05-01

In recent years all over the world special attention has been paid to the development and implementation of nanostructured materials possessing unique properties and opening fascinating prospects for the development of technical progress in various fields of human activities. A special place can be given to the development of service robots, the market of which is actively developing. There is problem associated mainly with the lack of heat-strengthened alloys which consists in low thermal stability of the alloy properties under the conditions of elevated variable temperatures and loads. The article presents studies to assess the effect of composition, the amounts of refractory nanoscale particles and methods for their introduction into the melt on the structure and properties in nanostructured composite aluminum alloys. The powders of metals, alloys, as well as silicon carbide and aluminum oxide were used to produce the nanostructured powder composite materials. As a result of the research, NPCM compositions containing micro-size particles of transition metals that are carriers of nanosized reinforcing particles and initiators of the formation of an intermetallide of endogenous origin in a melt.

Production of fiberglass/metal composite material suitable for building habitat and manufacturing facilities

NASA Technical Reports Server (NTRS)

1987-01-01

The production of a fiberglass/metal composite material suitable for building habitats and manufacturing facilities was the project for Clemson. The concept and development of the knowledge necessary to produce glass fibers originated in the spring semester. During the summer, while at Johnson Space Center, fiberglass from a rock composition similar to ones found at the Apollo 16 site on the moon was successfully produced. The project this year was a continuation of last year's studies. We addressed the following problems which emerged as the work progressed: (1) Methods for coating the fibers with a metal were explored. We manufactured composites in two stages: Glass fibers without any coating on them; and fibers coated with metals as they were made. This proved to be a difficult process. Future activities include using a chemical vapor deposition process on fibers which have been made. (2) A glass furnace was developed which relies primarily on solar energy for melting the glass. The temperature of the melted glass is maintained by electrical means. The design is for 250 kg of glass per day. An electrical engineering student developed a scheme for controlling the melting and manufacturing process from the earth. This was done to minimize the human risk. Graphite refractories are relied on to contain the melt. (3) The glass composition chosen for the project is a relatively pure anorthite which is available in the highland regions of the lunar surface. A major problems with this material is that it melts at a comparatively high temperature. This problem will be solved by using graphite refractory materials for the furnace. The advantage of this glass composition is that it is very stable and does not tend to crystallize. (4) We have also refined the experimental furnace and fiber making machinery which we will be using at Johnson Space Center this summer. We believe that we will be able to draw and coat glass fibers in a vacuum for use in composites. We intend to make and test the mechanical properties of these composites.

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

PubMed

Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

2015-04-01

To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

LINX®, a novel treatment for patients with refractory asthma complicated by gastroesophageal reflux disease: a case report.

PubMed

Sriratanaviriyakul, Narin; Kivler, Celeste; Vidovszky, Tamas J; Yoneda, Ken Y; Kenyon, Nicholas J; Murin, Susan; Louie, Samuel

2016-05-24

Gastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure. Our patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting β2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting. LINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

Rapidly-progressive catatonia responsive to zolpidem in a patient with ovarian teratoma-associated paraneoplastic encephalitis.

PubMed

Amorim, Edilberto; McDade, Eric M

2016-08-01

Psychiatric symptoms and catatonia are key components of the clinical presentation of paraneoplastic encephalitis; additionally symptoms can be long-lasting and often difficult to treat. We report a 73-year-old patient with rapidly progressive catatonia not responsive to immunotherapy, tumor resection, electroconvulsive therapy, or benzodiazepines who had significant improvement after zolpidem administration. This report suggests that zolpidem is an option in the treatment of patients with refractory catatonia and paraneoplastic encephalitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advanced Ceramics for Use as Fuel Element Materials in Nuclear Thermal Propulsion Systems

NASA Technical Reports Server (NTRS)

Valentine, Peter G.; Allen, Lee R.; Shapiro, Alan P.

2012-01-01

With the recent start (October 2011) of the joint National Aeronautics and Space Administration (NASA) and Department of Energy (DOE) Advanced Exploration Systems (AES) Nuclear Cryogenic Propulsion Stage (NCPS) Program, there is renewed interest in developing advanced ceramics for use as fuel element materials in nuclear thermal propulsion (NTP) systems. Three classes of fuel element materials are being considered under the NCPS Program: (a) graphite composites - consisting of coated graphite elements containing uranium carbide (or mixed carbide), (b) cermets (ceramic/metallic composites) - consisting of refractory metal elements containing uranium oxide, and (c) advanced carbides consisting of ceramic elements fabricated from uranium carbide and one or more refractory metal carbides [1]. The current development effort aims to advance the technology originally developed and demonstrated under Project Rover (1955-1973) for the NERVA (Nuclear Engine for Rocket Vehicle Application) [2].

Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

PubMed

Bhatt, Vijaya Raj; Vose, Julie M

2014-12-01

Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Rice Husk Ash Insulation Powder on the Reoxidation Behavior of Molten Steel in Continuous Casting Tundish

NASA Astrophysics Data System (ADS)

Kim, Tae Sung; Chung, Yongsug; Holappa, Lauri; Park, Joo Hyun

2017-06-01

Rice husk ash (RHA) has been widely used as an insulation powder in steel casting tundish. Its effect on the reoxidation of molten steel in tundish as well as on the corrosion of magnesia refractory was investigated. The reoxidation of the steel, indicated by an oxygen pickup, was progressed by increasing the ratio of RHA to the sum of RHA and carryover ladle slag ( R ratio) greater than about 0.2. The increase of the silica activity in the slag layer promoted the self-dissociation of SiO2 from the slag layer into the molten steel, resulting in the silicon and oxygen pickup as the R ratio increased. The total number of reoxidation inclusions dramatically increased and the relative fraction of Al2O3-rich inclusions increased by increasing the R ratio. Hence, the reoxidation of molten steel in tundish might become more serious due to the formation of alumina-rich inclusions as the casting sequence increases. MgO in the refractory directly dissolved into the molten slag layer without forming any intermediate compound layer ( e.g., spinel), which is a completely different situation from the general slag-refractory interfacial reaction. A flow was possibly induced by the bursting of gas bubbles at the ash-slag (-refractory) interface, since the silica in the RHA powder continuously dissolved into the molten slag pool. Thus, the RHA insulation powder has a negative effect on the corrosion of MgO refractory.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.

PubMed

Jain, Preetesh; Thompson, Philip A; Keating, Michael; Estrov, Zeev; Ferrajoli, Alessandra; Jain, Nitin; Kantarjian, Hagop; Burger, Jan A; O'Brien, Susan; Wierda, William G

2017-06-15

Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed. Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy. Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society. © 2017 American Cancer Society.

IMPACT OF PRETRANSPLANT CONDITIONING REGIMENS ON OUTCOMES OF ALLOGENEIC TRANSPLANTATION FOR CHEMOTHERAPY-UNRESPONSISVE DIFFUSE LARGE B-CELL LYMPHOMA AND GRADE-III FOLLICULAR LYMPHOMA

PubMed Central

Hamadani, Mehdi; Saber, Wael; Ahn, Kwang Woo; Carreras, Jeanette; Cairo, Mitchell S.; Fenske, Timothy S.; Gale, Robert Peter; Gibson, John; Hale, Gregory A.; Hari, Parameswaran N.; Hsu, Jack W.; Inwards, David J.; Kamble, Rammurti T.; Klein, Anderas; Maharaj, Dipnarine; Marks, David I.; Rizzieri, David A.; Savani, Bipin N.; Schouten, Harry C.; Waller, Edmund K.; Wirk, Baldeep; Laport, Ginna G.; Montoto, Silvia; Maloney, David G.; Lazarus, Hillard M.

2013-01-01

Patients with chemorefractory non-Hodgkin lymphomas (NHL) generally have a poor prognosis. We used the observational database of the CIBMTR to study the outcome of 533 patients with refractory diffuse large B-cell lymphoma (DLBCL) or grade-III follicular lymphoma (FL-III) who underwent allogeneic transplantation (allo-HCT) using either myeloablative (MA; N=307) or reduced intensity/non-myeloablative conditioning (RIC/NST; N=226), between 1998-2010. We analyzed non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplant had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3years, MA allo-HCT was associated with a higher NRM compared to RIC/NST (53% vs. 42%; p=0.03), similar PFS (19% vs. 23%; p=0.40), and lower OS (19% vs. 28%; p=0.02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative-risk [RR]=0.52), reduced risk of relapse/progression (RR=0.42), superior PFS (RR=0.51) and OS (RR=0.53), while MA conditioning was associated with reduced risk of relapse/progression (RR=0.66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT. PMID:23380340

METHOD OF MAKING A REFRACTORY MATERIAL

DOEpatents

Miller, H.I.

1958-01-01

This patent relates to a composition containing beryllia and the oxide of a fissile element such as uranium. The oxides are first ground and mixed, paraffin is added to the mixed powders, and the composition is then compacted and sintered to drive off the paraffin and produce a stuctually stable compact. The result is a coherent refractory arrangement of fissile nuclei dispersed among moderating nuclei. The composition, size, shape, etc., of the brick may be varied according to its intended use.

Airframe materials for HSR

NASA Technical Reports Server (NTRS)

Bales, Thomas T.

1992-01-01

Vugraphs are presented to show the use of refractory materials for the skin of the High speed Civil Transport (HSCT). Examples are given of skin temperature ranges, failure mode weight distribution, tensile properties as a function of temperature, and components to be constructed from composite materials. The responsibilities of various aircraft companies for specific aircraft components are defined.

Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder.

PubMed

Ananth, Amitha L; Robichaux-Viehoever, Amy; Kim, Young-Min; Hanson-Kahn, Andrea; Cox, Rachel; Enns, Gregory M; Strober, Jonathan; Willing, Marcia; Schlaggar, Bradley L; Wu, Yvonne W; Bernstein, Jonathan A

2016-06-01

Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novoGNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy. Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients. All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age four years in all but one patient, who developed chorea at 14 years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients. Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group.

PubMed

Conconi, Annarita; Raderer, Markus; Franceschetti, Silvia; Devizzi, Liliana; Ferreri, Andrés J M; Magagnoli, Massimo; Arcaini, Luca; Zinzani, Pier Luigi; Martinelli, Giovanni; Vitolo, Umberto; Kiesewetter, Barbara; Porro, Elena; Stathis, Anastasios; Gaidano, Gianluca; Cavalli, Franco; Zucca, Emanuele

2014-07-01

The International Extranodal Lymphoma Study Group coordinated a phase II trial to evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs). Thirty patients with relapsed/refractory MZLs received everolimus for six cycles or until dose-limiting toxicity or progression. Median age was 71 years (range, 51-88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty-four patients had stage III-IV. Median number of prior therapies was two (range 1-5). Seventeen patients had early treatment discontinuation, in most cases due to toxicity. Median number of cycles was 4.5 (range, 1-16). Among the 24 assessable patients, the overall response rate (ORR) was 25% (95% confidence interval: 10-47). Grade 3-4 adverse events were neutropenia and thrombocytopenia (17% of patients, each), infections (17%), mucositis and odontogenic infections (13%) and lung toxicity (3%). The median response duration was 6.8 months (range, 1.4-11.1+). After a median follow-up of 14.5 months, five deaths were reported: four deaths were due to lymphoma, one was due to toxicity. In an intent-to-treat analysis, the projected median progression-free survival was 14 months. The moderate antitumour activity of everolimus in relapsed/refractory MZLs and the observed toxicity limit its therapeutical applicability in these indolent entities. Lower doses of the drug and, perhaps, different strategies including combination with additional agents need to be explored. © 2014 John Wiley & Sons Ltd.

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Generation of long time creep data on refractory alloys at elevated temperatures

NASA Technical Reports Server (NTRS)

Sheffler, K. D.

1970-01-01

Creep tests were conducted on two tantalum alloys (ASTAR 811C and T-111 alloy), on a molybdenum alloy (TZM), and on CVD tungsten. The T-111 alloy 1% creep life data have been subjected to Manson's station function analysis, and the progress on this analysis is described. In another test program, the behavior of T-111 alloy with continuously varying temperatures and stresses has been studied. The results indicated that the previously described analysis predicts the observed creep behavior with reasonable accuracy. In addition to the T-111 test program, conventional 1% creep life data have been obtained for ASTAR 811C alloy. Previously observed effects of heat treatment on the creep strength of this material have been discussed and a model involving carbide strengthening primarily at the grain boundaries, rather than in a classical dispersion hardening mechanism, has been proposed to explain the observed results.

Evolution of penile prosthetic devices

PubMed Central

Burnett, Arthur L.

2015-01-01

Penile implant usage dates to the 16th century yet penile implants to treat erectile dysfunction did not occur until nearly four centuries later. The modern era of penile implants has progressed rapidly over the past 50 years as physicians' knowledge of effective materials for penile prostheses and surgical techniques has improved. Herein, we describe the history of penile prosthetics and the constant quest to improve the technology. Elements of the design from the first inflatable penile prosthesis by Scott and colleagues and the Small-Carrion malleable penile prosthesis are still found in present iterations of these devices. While there have been significant improvements in penile prosthesis design, the promise of an ideal prosthetic device remains elusive. As other erectile dysfunction therapies emerge, penile prostheses will have to continue to demonstrate a competitive advantage. A particular strength of penile prostheses is their efficacy regardless of etiology, thus allowing treatment of even the most refractory cases. PMID:25763121

Evolution of penile prosthetic devices.

PubMed

Le, Brian; Burnett, Arthur L

2015-03-01

Penile implant usage dates to the 16th century yet penile implants to treat erectile dysfunction did not occur until nearly four centuries later. The modern era of penile implants has progressed rapidly over the past 50 years as physicians' knowledge of effective materials for penile prostheses and surgical techniques has improved. Herein, we describe the history of penile prosthetics and the constant quest to improve the technology. Elements of the design from the first inflatable penile prosthesis by Scott and colleagues and the Small-Carrion malleable penile prosthesis are still found in present iterations of these devices. While there have been significant improvements in penile prosthesis design, the promise of an ideal prosthetic device remains elusive. As other erectile dysfunction therapies emerge, penile prostheses will have to continue to demonstrate a competitive advantage. A particular strength of penile prostheses is their efficacy regardless of etiology, thus allowing treatment of even the most refractory cases.

Decoding IR Spectra of Cosmic Ices and Organics in the Laboratory

NASA Technical Reports Server (NTRS)

Allamandola, Louis J.

2006-01-01

Tremendous strides have been made in our understanding of interstellar material over the past twenty-five years thanks to significant developments in observational IR astronomy and dedicated laboratory experiments. Twenty-five years ago the composition of interstellar dust was largely guessed at. Today the composition of interstellar dust is reasonably well understood. In the diffuse interstellar medium (ISM) the dust population is mainly comprised of small grains of silicates and amorphous carbon. In dark molecular clouds, the birthplace of stars and planets, these cold refractory dust particles are coated with mixed molecular ices whose composition is reasonably well constrained. Lastly, the signature of carbon-rich polycyclic aromatic hydrocarbons (PAHs), shockingly large molecules by early interstellar chemistry standards, is widespread throughout the Universe. This extraordinary progress has been made possible by the close collaboration of laboratory experimentalists and theoreticians with IR astronomers using groundbased, air-borne, and orbiting telescopes.

Better VPS Fabrication of Crucibles and Furnace Cartridges

NASA Technical Reports Server (NTRS)

Holmes, Richard R.; Zimmerman, Frank R.; O'Dell, J. Scott; McKechnie, Timothy N.

2003-01-01

An experimental investigation has shown that by (1) vacuum plasma spraying (VPS) of suitable refractory metal alloys on graphite mandrels, and then (2) heat-treating the VPS alloy deposits under suitable conditions, it is possible to fabricate improved crucibles and furnace cartridges that could be used at maximum temperatures between 1,400 and 1,600 C and that could withstand chemical attack by the materials to be heated in the crucibles and cartridges. Taken by itself, the basic concept of fabricating furnace cartridges by VPS of refractory materials onto graphite mandrels is not new; taken by itself, the basic concept of heat treatment of VPS deposits for use as other than furnace cartridges is also not new; however, prior to this investigation, experimental crucibles and furnace cartridges fabricated by VPS had not been heat treated and had been found to be relatively weak and brittle. Accordingly, the investigation was directed toward determining whether certain combinations of (1) refractory alloy compositions, (2) VPS parameters, and (3) heat-treatment parameters could result in VPS-fabricated components with increased ductility.

Application of high temperature phase change materials for improved efficiency in waste-to-energy plants.

PubMed

Dal Magro, Fabio; Xu, Haoxin; Nardin, Gioacchino; Romagnoli, Alessandro

2018-03-01

This study reports the thermal analysis of a novel thermal energy storage based on high temperature phase change material (PCM) used to improve efficiency in waste-to-energy plants. Current waste-to-energy plants efficiency is limited by the steam generation cycle which is carried out with boilers composed by water-walls (i.e. radiant evaporators), evaporators, economizers and superheaters. Although being well established, this technology is subjected to limitations related with high temperature corrosion and fluctuation in steam production due to the non-homogenous composition of solid waste; this leads to increased maintenance costs and limited plants availability and electrical efficiency. The proposed solution in this paper consists of replacing the typical refractory brick installed in the combustion chamber with a PCM-based refractory brick capable of storing a variable heat flux and to release it on demand as a steady heat flux. By means of this technology it is possible to mitigate steam production fluctuation, to increase temperature of superheated steam over current corrosion limits (450°C) without using coated superheaters and to increase the electrical efficiency beyond 34%. In the current paper a detailed thermo-mechanical analysis has been carried out in order to compare the performance of the PCM-based refractory brick against the traditional alumina refractory bricks. The PCM considered in this paper is aluminium (and its alloys) whereas its container consists of high density ceramics (such as Al 2 O 3 , AlN and Si 3 N 4 ); the different coefficient of linear thermal expansion for the different materials requires a detailed thermo-mechanical analysis to be carried out to ascertain the feasibility of the proposed technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog.

PubMed

Maton, Barbara L; Simmonds, Erin E; Lee, Justine A; Alwood, Amy J

2013-01-01

To describe the novel use of high-dose insulin (HDI) therapy and intravenous lipid emulsion (ILE) to treat refractory, severe diltiazem toxicosis in a dog. A 4-year-old Pomeranian was presented for treatment 2.5 hours following ingestion of a diltiazem extended-release capsule. Toxic ingestion was calculated at a maximum exposure of 79 mg/kg, with a reported canine LD50 of 50 mg/kg. Clinical signs of progressive hypotension and severe bradycardia with atrial standstill were observed, which persisted despite treatment with atropine, calcium, glucagon, and dopamine. The novel use of HDI and ILE as part of therapy for diltiazem toxicosis resulted in clinical resolution of life-threatening signs. Within 1 hour of initiating HDI therapy, the clinical signs improved, and with continued treatment, the patient remained normotensive and survived to discharge. To the authors' knowledge, this is the first reported clinical case describing the use of both HDI and ILE therapy in the treatment of severe refractory diltiazem toxicosis in veterinary medicine. No significant adverse effects were observed from the treatment. In veterinary patients with severe refractory calcium channel blocker toxicosis, the use of HDI and ILE should be considered for life-threatening clinical signs. © Veterinary Emergency and Critical Care Society 2013.

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

PubMed

Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

2013-08-01

The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Advanced Materials and Fabrication Techniques for the Orion Attitude Control Motor

NASA Technical Reports Server (NTRS)

Gorti, Sridhar; Holmes, Richard; O'Dell, John; McKechnie, Timothy; Shchetkovskiy, Anatoliy

2013-01-01

Rhenium, with its high melting temperature, excellent elevated temperature properties, and lack of a ductile-to-brittle transition temperature (DBTT), is ideally suited for the hot gas components of the ACM (Attitude Control Motor), and other high-temperature applications. However, the high cost of rhenium makes fabricating these components using conventional fabrication techniques prohibitive. Therefore, near-net-shape forming techniques were investigated for producing cost-effective rhenium and rhenium alloy components for the ACM and other propulsion applications. During this investigation, electrochemical forming (EL-Form ) techniques were evaluated for producing the hot gas components. The investigation focused on demonstrating that EL-Form processing techniques could be used to produce the ACM flow distributor. Once the EL-Form processing techniques were established, a representative rhenium flow distributor was fabricated, and samples were harvested for material properties testing at both room and elevated temperatures. As a lower cost and lighter weight alternative to an all-rhenium component, rhenium- coated graphite and carbon-carbon were also evaluated. The rhenium-coated components were thermal-cycle tested to verify that they could withstand the expected thermal loads during service. High-temperature electroforming is based on electrochemical deposition of compact layers of metals onto a mandrel of the desired shape. Mandrels used for electro-deposition of near-net shaped parts are generally fabricated from high-density graphite. The graphite mandrel is easily machined and does not react with the molten electrolyte. For near-net shape components, the inner surface of the electroformed part replicates the polished graphite mandrel. During processing, the mandrel itself becomes the cathode, and scrap or refined refractory metal is the anode. Refractory metal atoms from the anode material are ionized in the molten electrolytic solution, and are deposited onto the cathodic mandrel by electrochemical reduction. Rotation of the mandrel ensures uniform distribution of refractory material. The EL-Form process allows for manufacturing in an inert atmosphere with deposition rates from 0.0004 to 0.002 in./h (10.2 to 50.8 m/h). Thicknesses typically range from microns to greater than 0.5 in. (13 mm). The refractory component produced is fabricated, dependably, to within one micron of the desired tolerances with no shrinkage or distortion as in other refractory metal manufacture techniques. The electroforming process has been used to produce solid, nonporous deposits of rhenium, iridium, niobium, tungsten, and their alloys.

Design and development of advanced castable refractory materials

NASA Astrophysics Data System (ADS)

Davis, Robert Bruce

New formulations of castable refractory composite materials were studied. This technology is used to produce low cost composite concrete structures designed for high temperature stability, superior wear resistance and improved strength. An in situ fired, castable cement installation is a heterogeneous structure divided into three zones according to the temperature history and microstructure. The properties of each zone depend on the predominant bonding mode between constituents. Each zone has a characteristic microstructure that influences the integrity of the monolith. The hot side may have a highly dense and developed network of ceramic bonds between constituent particles while the cold side may never reach temperatures sufficient to drive off free water. The thermal, structural and tribological properties depend on the microstructure and the type of bonding that holds the monolith together. The phase distributions are defined by sets of metastable phase conditions driven by the local hydrated chemistry, nearest neighbor oxide compounds, impurities and sintering temperature. Equilibrium phase diagrams were used to select optimum compositions based on higher melting point phases. The phase diagrams were also used to target high temperature phase fields that are stable over wide temperature and stoichiometric ranges. Materials selection of candidate hydraulic clinkers, high temperature oxides, and reinforcement phases were based on requirements for high temperature stability. The calcium aluminate (CaO-Al2O3) and calcium dialuminate (CaO-(Al2O3)2) are common refractory clinkers used in castable refractory cements. The thermodynamics and kinetics of cement hydrate formation are well studied and suited to become the building block of a design for a superior refractory castable cement. The inert oxides mixed with the calcium aluminate clinkers are magnesia (MgO), alumina (Al 2O3), spinel (MgAl2O4) and chromic (Cr2O3). The bulk of the experiments concentrated in the Al2O3--MgO--CaO ternary system. Materials selection criteria for reinforcement materials was based on improved high temperature stability, increased strength, reduced thermal expansion mismatch, low thermal conductivity and increasing wear resistance. The reinforcement phases selected for this investigation are zircon (ZrSiO4), zirconia (ZrO2), spinel (MgAl2O4) and dead burnt magnesia (MgO). Batches of the formulations were tested for thermal conductivity, wear resistance and mechanical strength. Relative rankings of the formulations against commercial products indicate improved or similar performance with increased maximum temperature limits and improved thermal insulating power. The new cement formulations proved to exhibit superior high temperature stability with an increasing volume fraction of high temperature oxides. The addition of reinforcement aggregates and powder sizing to offset the loss of strength. The room temperature compression strength and wear resistance of the optimized formulations exceeded the properties of conventional refractory, brick and castable cement tested concurrently.

Refractory of Furnaces to Reduce Environmental Impact

NASA Astrophysics Data System (ADS)

Hanzawa, Shigeru

2011-10-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Pre-fired, refractory block slag dams for wet bottom furnace floors

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

Vihnicka, R.S.; Meskimen, R.L.

1998-12-31

Slagging (wet bottom), utility boilers count on a refractory coating over the furnace floor tube structure for protection from corrosion damage from both the harsh, hot gas atmosphere from the burning fuel and the acidic coal slag. To protect and extend the life of this protective refractory coating the boiler original equipment manufacturers (OEMs) utilized a water-cooled monkey ring or slag chill ring (typically a 6--8 inch high ring of small diameter tubes) surrounding the slag tap locations on most wet bottom furnace floors (both utility and package boilers). The old water-cooled tube ring was such a high maintenance item,more » however, that it`s use has been discontinued in all but the most extreme environments throughout both utility and industrial applications. Where the use of the ring was discontinued, there has been a corresponding shortening of life on the protective floor refractory coatings (high maintenance cost), further aggravated by recent OSHA restrictions limiting the use of chrome oxide refractory materials in these types of boilers. This paper describes the developmental process and the final resultant product (a non-watercooled, slag dam made from pre-fired refractory shapes), undertaken by the inventors. Derived operational benefits a concept 2 project, with NO{sub x} Title 4 and Title 1 significance (which is currently underway) will also be detailed.« less

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

PubMed

Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation

PubMed Central

Herrera, Alex F.; Mei, Matthew; Low, Lawrence; Kim, Haesook T.; Griffin, Gabriel K.; Song, Joo Y.; Merryman, Reid W.; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R.; Budde, Lihua E.; Chan, Wing C.; Chen, Robert; Davids, Matthew S.; Freedman, Arnold S.; Fisher, David C.; Jacobsen, Eric D.; Jacobson, Caron A.; LaCasce, Ann S.; Murata-Collins, Joyce; Nademanee, Auayporn P.; Palmer, Joycelynne M.; Pihan, German A.; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R.; Zain, Jasmine; Rosen, Steven T.; Kwak, Larry W.; Weinstock, David M.; Forman, Stephen J.; Weisenburger, Dennis D.; Kim, Young; Rodig, Scott J.; Krishnan, Amrita

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P = .013), and 4-year OS was 25% versus 61% (P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT. PMID:28034071

Coal-fired high performance power generating system. Quarterly progress report, October 1, 1994--December 31, 1994

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

NONE

1995-08-01

This report covers work carried out under Task 3, Preliminary R and D, under contract DE-AC22-92PC91155, {open_quotes}Engineering Development of a Coal-Fired High Performance Power Generation System{close_quotes} between DOE Pittsburgh Energy Technology Center and United Technologies Research Center. The goals of the program are to develop a coal-fired high performance power generation system (HIPPS) by the year 2000 that is capable of (1) > 47% thermal efficiency; (2) NO{sub x}, SO{sub x} and particulates {<=}25% NSPS; (3) cost {>=}65% of heat input; (4) all solid wastes benign. In our design consideration, we have tried to render all waste streams benign andmore » if possible convert them to a commercial product. It appears that vitrified slag has commercial values. If the flyash is reinjected through the furnace, along with the dry bottom ash, then the amount of the less valuable solid waste stream (ash) can be minimized. A limitation on this procedure arises if it results in the buildup of toxic metal concentrations in either the slag, the flyash or other APCD components. We have assembled analytical tools to describe the progress of specific toxic metals in our system. The outline of the analytical procedure is presented in the first section of this report. The strengths and corrosion resistance of five candidate refractories have been studied in this quarter. Some of the results are presented and compared for selected preparation conditions (mixing, drying time and drying temperatures). A 100 hour pilot-scale stagging combustor test of the prototype radiant panel is being planned. Several potential refractory brick materials are under review and five will be selected for the first 100 hour test. The design of the prototype panel is presented along with some of the test requirements.« less

A review of refractory materials for vapor-anode AMTEC cells

NASA Astrophysics Data System (ADS)

King, Jeffrey C.; El-Genk, M. S.

2000-01-01

Recently, refractory alloys have been considered as structural materials for vapor-anode Alkali Metal Thermal-to-Electric Conversion (AMTEC) cells, for extended (7-15 years) space missions. This paper reviewed the existing database for refractory metals and alloys of potential use as structural materials for vapor-anode sodium AMTEC cells. In addition to requiring that the vapor pressure of the material be below 10-9 torr (133 nPa) at a typical hot side temperature of 1200 K, other screening considerations were: (a) low thermal conductivity, low thermal radiation emissivity, and low linear thermal expansion coefficient; (b) low ductile-to-brittle transition temperature, high yield and rupture strengths and high strength-to-density ratio; and (c) good compatibility with the sodium AMTEC operating environment, including high corrosion resistance to sodium in both the liquid and vapor phases. Nb-1Zr (niobium-1% zirconium) alloy is recommended for the hot end structures of the cell. The niobium alloy C-103, which contains the oxygen gettering elements zirconium and hafnium as well as titanium, is recommended for the colder cell structure. This alloy is stronger and less thermally conductive than Nb-1Zr, and its use in the cell wall reduces parasitic heat losses by conduction to the condenser. The molybdenum alloy Mo-44.5Re (molybdenum-44.5% rhenium) is also recommended as a possible alternative for both structures if known problems with oxygen pick up and embrittlement of the niobium alloys proves to be intractable. .

Non-Contact Measurements of Creep Properties of Refractory Materials

NASA Technical Reports Server (NTRS)

Lee, Jonghyun; Bradshaw, Richard C.; Hyers, Robert W.; Rogers, Jan R.; Rathz, Thomas J.; Wall, James J.; Choo, Hahn; Liaw, Peter

2006-01-01

State-of-the-art technologies for hypersonic aircraft, nuclear electric/thermal propulsion for spacecraft, and more efficient jet engines are driving ever more demanding needs for high-temperature (>2000 C) materials. At such high temperatures, creep rises as one of the most important design factors to be considered. Since conventional measurement techniques for creep resistance are limited to about 17OO0C, a new technique is in demand for higher temperatures. This paper presents a non-contact method using electrostatic levitation (ESL) which is applicable to both metallic and non-metallic materials. The samples were rotated quickly enough to cause creep deformation by centrifugal acceleration. The deformation of the samples was captured with a high speed camera and then the images were analyzed to estimate creep resistance. Finite element analyses were performed and compared to the experiments to verify the new method. Results are presented for niobium and tungsten, representative refractory materials at 2300 C and 2700 C respectively.

Refractory metal joining for first wall applications

NASA Astrophysics Data System (ADS)

Cadden, C. H.; Odegard, B. C.

2000-12-01

The potential use of high temperature coolant (e.g. 900°C He) in first wall structures would preclude the applicability of copper alloy heat sink materials and refractory metals would be potential replacements. Brazing trials were conducted in order to examine techniques to join tungsten armor to high tungsten (90-95 wt%) or molybdenum TZM heat sink materials. Palladium-, nickel- and zirconium-based filler metals were investigated using brazing temperatures ranging from 1000°C to 1275°C. Palladium-nickel and palladium-cobalt braze alloys were successful in producing generally sound metallurgical joints in tungsten alloy/tungsten couples, although there was an observed tendency for the pure tungsten armor material to exhibit grain boundary cracking after bonding. The zirconium- and nickel-based filler metals produced defect-containing joints, specifically cracking and porosity, respectively. The palladium-nickel braze alloy produced sound joints in the Mo TZM/tungsten couple. Substitution of a lanthanum oxide-containing, fine-grained tungsten material (for the pure tungsten) eliminated the observed tungsten grain boundary cracking.

Metal- and intermetallic-matrix composites for aerospace propulsion and power systems

NASA Technical Reports Server (NTRS)

Doychak, J.

1992-01-01

The requirements for high specific strength refractory materials of prospective military, civil, and space propulsion systems are presently addressed in the context of emerging capabilities in metal- and intermetallic-matrix composites. The candidate systems encompass composite matrix compositions of superalloy, Nb-Zr refractory alloy, Cu-base, and Ti-base alloy types, as well as such intermetallics as TiAl, Ti3Al, NiAl, and MoSi2. The brittleness of intermetallic matrices remains a major consideration, as does their general difficulty of fabrication.

Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

ClinicalTrials.gov

2013-01-15

Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

Pad A Main Flame Deflector Sensor Data and Evaluation

NASA Technical Reports Server (NTRS)

Parlier, Christopher R.

2011-01-01

Space shuttle launch pads use flame deflectors beneath the vehicle to channel hot gases away from the vehicle. Pad 39 A at the Kennedy Space Center uses a steel structure coated with refractory concrete. The solid rocket booster plume is comprised of gas and molten alumina oxide particles that erodes the refractory concrete. During the beginning of the shuttle program the loads for this system were never validated with a high level of confidence. This paper presents a representation of the instrumentation data collected and follow on materials science evaluation of the materials exposed to the SRB plume. Data collected during STS-133 and STS-134 will be presented that support the evaluation of the components exposed to the SRB plume.

Modeling of Heat Transfer and Ablation of Refractory Material Due to Rocket Plume Impingement

NASA Technical Reports Server (NTRS)

Harris, Michael F.; Vu, Bruce T.

2012-01-01

CR Tech's Thermal Desktop-SINDA/FLUINT software was used in the thermal analysis of a flame deflector design for Launch Complex 39B at Kennedy Space Center, Florida. The analysis of the flame deflector takes into account heat transfer due to plume impingement from expected vehicles to be launched at KSC. The heat flux from the plume was computed using computational fluid dynamics provided by Ames Research Center in Moffet Field, California. The results from the CFD solutions were mapped onto a 3-D Thermal Desktop model of the flame deflector using the boundary condition mapping capabilities in Thermal Desktop. The ablation subroutine in SINDA/FLUINT was then used to model the ablation of the refractory material.

Refractory Materials for Flame Deflector Protection System Corrosion Control: Coatings Systems Literature Survey

NASA Technical Reports Server (NTRS)

Calle, Luz M.; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Coffman, Brekke E.; Coffman, Brekke E.; Curran, Jerome P.; Kolody, Mark R.; Whitten, Mary; Perisich, Steven;

Sharp Refractory Composite Leading Edges on Hypersonic Vehicles

NASA Technical Reports Server (NTRS)

Walker, Sandra P.; Sullivan, Brian J.

2003-01-01

On-going research of advanced sharp refractory composite leading edges for use on hypersonic air-breathing vehicles is presented in this paper. Intense magnitudes of heating and of heating gradients on the leading edge lead to thermal stresses that challenge the survivability of current material systems. A fundamental understanding of the problem is needed to further design development. Methodology for furthering the technology along with the use of advanced fiber architectures to improve the thermal-structural response is explored in the current work. Thermal and structural finite element analyses are conducted for several advanced fiber architectures of interest. A tailored thermal shock parameter for sharp orthotropic leading edges is identified for evaluating composite material systems. The use of the tailored thermal shock parameter has the potential to eliminate the need for detailed thermal-structural finite element analyses for initial screening of material systems being considered for a leading edge component.

Presence, segregation and reactivity of H, C and N dissolved in some refractory oxides

NASA Technical Reports Server (NTRS)

Freund, F.

1986-01-01

The sources of impurities, particularly carbon, in high melting oxides and silicates are discussed, along with detection and quantification methods. The impurities are important for their effects on bulk material properties through the media of, e.g., surface or grain boundary characteristics. The impurities are usually encountered by the contact of the oxide (refractory) material with volatiles such as H2O and CO2, which become incorporated in the material and form anion complexes with oxygen acting as a covalent bonded ligand. The specific processes undergone by MgO in assimilating C impurities are delineated, using data obtained with X-ray photoelectron spectroscopy, Auger electron spectroscopy, secondary ion mass spectrometry and nuclear reaction profiling. Finally, maintenance of a supersaturated solid solution with C impurities by space charge control is described as a means of offset impurity effects.

Application of diffusion barriers to the refractory fibers of tungsten, columbium, carbon and aluminum oxide

NASA Technical Reports Server (NTRS)

Douglas, F. C.; Paradis, E. L.; Veltri, R. D.

1973-01-01

A radio frequency powered ion-plating system was used to plate protective layers of refractory oxides and carbide onto high strength fiber substrates. Subsequent overplating of these combinations with nickel and titanium was made to determine the effectiveness of such barrier layers in preventing diffusion of the overcoat metal into the fibers with consequent loss of fiber strength. Four substrates, five coatings, and two metal matrix materials were employed for a total of forty material combinations. The substrates were tungsten, niobium, NASA-Hough carbon, and Tyco sapphire. The diffusion-barrier coatings were aluminum oxide, yttrium oxide, titanium carbide, tungsten carbide with 14% cobalt addition, and zirconium carbide. The metal matrix materials were IN 600 nickel and Ti 6/4 titanium. Adhesion of the coatings to all substrates was good except for the NASA-Hough carbon, where flaking off of the oxide coatings in particular was observed.

Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.

PubMed

Tomolonis, Julie A; Agarwal, Saurabh; Shohet, Jason M

2018-05-01

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting 'stemness' and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

High-dose ifosfamide by infusion with Mesna in advanced refractory sarcomas.

PubMed

Güllü, I; Yalçin, S; Tekuzman, G; Barişta, I; Alkiş, N; Celik, I; Zengin, N; Güler, N; Kars, A; Baltali, E

1996-01-01

Twenty patients with advanced sarcomas entered a pilot study with ifosfamide (IF) and mercaptoethane sulfonate sodium (Mesna) as a second-line treatment for six planned cycles. All patients had received prior doxorubicin- and cyclophosphamide-based chemotherapies. IF was administered at a dose of 3 g/m2 given as continuous intravenous infusion for 24 hr on day 1-5 with Mesna. In the absence of disease progression, chemotherapy was planned to be repeated every 4 weeks for six consecutive cycles. Following chemotherapy, only 2 patients (11%) achieved partial response with response durations of 6 and 9 months. There was no complete response. When considered for only high-grade tumors, the response rate reached up to 22%. Toxicity was reported for 48 cycles and the dose-limiting toxicities were myelosuppression (22%) and encephalopathy (17%). Chemotherapy protocol was changed after two or three courses in 16 patients with stable or progressive disease. IF/Mesna chemotherapy at this dose and schedule was not found to be very promising in refractory sarcomas as a second-line chemotherapy.

In situ characterization of martian materials and detection of organic compounds with the MOMA investigation onboard the ExoMars rover

NASA Astrophysics Data System (ADS)

Arevalo, R. D., Jr.; Grubisic, A.; van Amerom, F. H. W.; Danell, R.; Li, X.; Kaplan, D.; Pinnick, V. T.; Brinckerhoff, W. B.; Getty, S.; Goesmann, F.

2017-12-01

Ground-based observations (e.g., via the NASA Infrared Telescope Facility) and in situ investigations, including flybys (e.g., Mariner Program), orbiters (most recently MAVEN and ExoMars TGO), stationary landers (i.e., Viking, Pathfinder and Phoenix), and mobile rovers (i.e., Sojourner, Spirit/Opportunity and Curiosity), have enabled the progressive exploration of the Martian surface. Evidence for liquid water, manifest as hydrated and amorphous materials representative of alteration products of primary minerals/lithologies, and geomorphological features such as recurring slope lineae (RSL), valley networks and open-basin lakes, indicates that Mars may have hosted habitable environments, at least on local scales (temporally and spatially). However, the preservation potential of molecular biosignatures in the upper meter(s) of the surface is limited by destructive cosmic radiation and oxidative chemical reactions. Moreover, the determination of indigenous versus exogenous origins, and biotic versus abiotic formation mechanisms of detected organic material, provide additional challenges for future missions to the red planet. The Mars Organic Molecule Analyzer (MOMA) onboard the ExoMars rover, set to launch in 2020, provides an unprecedented opportunity to discover unambiguous indicators of life. The MOMA instrument will investigate the compositions of materials collected during multiple vertical surveys, extending as deep as two meters below the surface, via: i) gas chromatography mass spectrometry, a method geared towards the detection of volatile organics and the determination of molecular chirality, mapping to previous in situ Mars investigations; and, ii) laser desorption mass spectrometry, a technique commonly employed in research laboratories to detect larger, more refractory organic materials, but a first for spaceflight applications. Selective ion excitation and tandem mass spectrometry (MS/MS) techniques support the isolation and disambiguation of complex molecular signatures. Progressive testing of the MOMA Flight Model and Engineering Test Unit, as shown here, demonstrates the capabilities of the instrument to identify mineralogical indices and measure ppb-levels of organic compounds embedded in natural and synthetic Mars analog samples.

High temperature performance of high-efficiency, multi-layer solar selective coatings for tower applications

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

Gray, M. H.; Tirawat, R.; Kessinger, K. A.

The roadmap to next-generation concentrating solar power plants anticipates a progression to central towers with operating temperatures in excess of 650°C. These higher temperatures are required to drive higher power-cycle efficiencies, resulting in lower cost energy. However, these conditions also place a greater burden on the materials making up the receiver. Any novel absorber material developed for next-generation receivers must be stable in air, cost effective, and survive thousands of heating and cooling cycles. The collection efficiency of a power tower plant can be increased if the energy absorbed by the receiver is maximized while the heat loss from themore » receiver to the environment is minimized. Thermal radiation losses can be significant (>7% annual energy loss) with receivers at temperatures above 650°C. We present progress toward highly efficient and durable solar selective absorbers (SSAs) intended for operating temperatures from 650°C to 1000°C. Selective efficiency (η sel) is defined as the energy retained by the absorber, accounting for both absorptance and emittance, relative to the energy incident on the surface. The low emittance layers of multilayer SSAs are binary compounds of refractory metals whose material properties indicate that coatings formed of these materials should be oxidation resistant in air to 800-1200°C. On this basis, we initially developed a solar selective coating for parabolic troughs. This development has been successfully extended to meet the absorptance and emittance objectives for the more demanding, high temperature regime. We show advancement in coating materials, processing and designs resulting in the initial attainment of target efficiencies η sel > 0.91 for proposed tower conditions. Additionally, spectral measurements show that these coatings continue to perform at targeted levels after cycling to temperatures of 1000°C in environments of nitrogen and forming gas.« less

High temperature performance of high-efficiency, multi-layer solar selective coatings for tower applications

DOE PAGES

Gray, M. H.; Tirawat, R.; Kessinger, K. A.; ...

2015-05-01

The roadmap to next-generation concentrating solar power plants anticipates a progression to central towers with operating temperatures in excess of 650°C. These higher temperatures are required to drive higher power-cycle efficiencies, resulting in lower cost energy. However, these conditions also place a greater burden on the materials making up the receiver. Any novel absorber material developed for next-generation receivers must be stable in air, cost effective, and survive thousands of heating and cooling cycles. The collection efficiency of a power tower plant can be increased if the energy absorbed by the receiver is maximized while the heat loss from themore » receiver to the environment is minimized. Thermal radiation losses can be significant (>7% annual energy loss) with receivers at temperatures above 650°C. We present progress toward highly efficient and durable solar selective absorbers (SSAs) intended for operating temperatures from 650°C to 1000°C. Selective efficiency (η sel) is defined as the energy retained by the absorber, accounting for both absorptance and emittance, relative to the energy incident on the surface. The low emittance layers of multilayer SSAs are binary compounds of refractory metals whose material properties indicate that coatings formed of these materials should be oxidation resistant in air to 800-1200°C. On this basis, we initially developed a solar selective coating for parabolic troughs. This development has been successfully extended to meet the absorptance and emittance objectives for the more demanding, high temperature regime. We show advancement in coating materials, processing and designs resulting in the initial attainment of target efficiencies η sel > 0.91 for proposed tower conditions. Additionally, spectral measurements show that these coatings continue to perform at targeted levels after cycling to temperatures of 1000°C in environments of nitrogen and forming gas.« less

Materials Sciences Research.

DTIC Science & Technology

1975-07-01

Physics of Refractory Materials (ERDA) ..... 160 J. Holder - Mechanical Properties of Solids (NSF) ...... 163 A. Granato - Anharmonic Effects in Solids...ERDA) ........ 166 6. Semiconductor Materials and Devices. N. Holonyak - Luinescence, Lasers, Carrier and Impurity Effects in Compound Semiconductors...1975. Dr. P. A. Egelstaff, University of Guelph, Ontario, Canada, "Three-Body Effects in Simple Fluids," April 9, 1975. Professor G. Leibfried, Oak

Radiation effects in structural materials of spallation targets

NASA Astrophysics Data System (ADS)

Jung, P.

2002-02-01

Effects of radiation damage by protons and neutrons in structural materials of spallation neutron sources are reviewed. Effects of atomic displacements, defect mobility and transmutation products, especially hydrogen and helium, on physical and mechanical properties are discussed. The most promising candidate materials (austenitic stainless steels, ferritic/martensitic steels and refractory alloys) are compared, and needed investigations are identified.

NETL- Severe Environment Corrosion Erosion Facility

ScienceCinema

None

2018-01-16

NETL's Severe Environment Corrosion Erosion Facility in Albany studies how new and old materials will stand up to new operating conditions. Work done in the lab supports NETL's oxy-fuel combustion oxidation work, refractory materials stability work, and the fuels program, in particular the hydrogen membrane materials stability work, to determine how best to upgrade existing power plants.

Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations.

PubMed

Baldini, L; Guffanti, A; Cro, L; Fracchiolla, N S; Colombi, M; Motta, M; Maiolo, A T; Neri, A

1997-11-01

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.

Long-term response to combination therapy with estramustine and somatostatin analogue in a patient with androgen ablation-refractory prostate cancer.

PubMed

Cerulli, Costantino; Sciarra, Alessandro; Salvatori, Gianfilippo; Di Silverio, Franco

2004-12-01

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Practical method of diffusion-welding steel plate in air

NASA Technical Reports Server (NTRS)

Holko, K. H.; Moore, T. J.

1971-01-01

Method is ideal for critical service requirements where parent metal properties are equaled in notch toughness, stress rupture and other characteristics. Welding technique variations may be used on a variety of materials, such as carbon steels, alloy steels, stainless steels, ceramics, and reactive and refractory materials.

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

PubMed

Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study.

PubMed

Friesecke, Sigrun; Stecher, Stephanie-Susanne; Gross, Stefan; Felix, Stephan B; Nierhaus, Axel

2017-09-01

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90-100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb ® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (-0.4 µg/kg/min; p = 0.03) and 12 h (-0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.

Survey of Materials for Fusion Fission Hybrid Reactors Vol 1 Rev. 0

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

Farmer, Joseph Collin

2007-07-03

Materials for fusion-fission hybrid reactors fall into several broad categories, including fuels, blanket and coolant materials, cladding, structural materials, shielding, and in the specific case of inertial-confinement fusion systems, laser and optical materials. This report surveys materials in all categories of materials except for those required for lasers and optics. Preferred collants include two molten salt mixtures known as FLIBE (Li2BeF4) and FLINABE (LiNaBeF4). In the case of homogenous liquid fuels, UF4 can be dissolved in these molten salt mixtures. The transmutation of lithium in this coolant produces very corrosive hydrofluoric acid species (HF and TF), which can rapidly degrademore » structural materials. Broad ranges of high-melting radiation-tolerant structural material have been proposed for fusion-fission reactor structures. These include a wide variety of steels and refractory alloys. Ferritic steels with oxide-dispersion strengthening and graphite have been given particular attention. Refractory metals are found in Groups IVB and VB of the periodic table, and include Nb, Ta, Cr, Mo, and W, as serve as the basis of refractory alloys. Stable high-melting composites and amorphous metals may also be useful. Since amorphous metals have no lattice structure, neutron bombardment cannot dislodge atoms from lattice sites, and the materials would be immune from this specific mode of degradation. The free energy of formation of fluorides of the alloying elements found in steels and refractory alloys can be used to determine the relative stability of these materials in molten salts. The reduction of lithium transmutation products (H + and T +) drives the electrochemical corrosion process, and liberates aggressive fluoride ions that pair with ions formed from dissolved structural materials. Corrosion can be suppressed through the use of metallic Be and Li, though the molten salt becomes laden with colloidal suspensions of Be and Li corrosion products in the process. Alternatively, imposed currents and other high-temperature cathodic protection systems are envisioned for protection of the structural materials. This novel concept could prove to be enabling technology for such high-temperature molten-salt reactors. The use of UF 4 as a liquid-phase homogenous fuel is also complicated by redox control. For example, the oxidation of tetravalent uranium to hexavalent uranium could result in the formation of volatile UF 6. This too could be controlled through electrochemically manipulated oxidation and reduction reactions. In situ studies of pertinent electrochemical reactions in the molten salts are proposed, and are relevant to both the corrosive attack of structural materials, as well as the volatilization of fuel. Some consideration is given to the potential advantages of gravity fed falling-film blankets. Such systems may be easier to control than vortex systems, but would require that cylindrical reaction vessels be oriented with the centerline normal to the gravitational field.« less

Advanced Research Projects Agency on Materials Preparation and Characterization Research

DTIC Science & Technology

Briefly summarized is research concerned with such topics as: Preparation of silica glass from amorphous silica; Glass structure by Raman ...ferroelectrics; Silver iodide crystals; Vapor phase growth; Refractory optical host materials; Hydroxyapatite ; Calcite; Characterization of single crystals with a double crystal spectrometer; Characterization of residual strain.

Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

PubMed

Koshkin, Vadim S; Grivas, Petros

2018-04-11

Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited. We review key recent data regarding immune checkpoint inhibitors that are changing this treatment landscape. Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Clinical outcomes and safety profiles of these agents appear relatively comparable across separate trials; however, only pembrolizumab is supported by level I evidence from a large randomized phase III trial showing overall survival benefit over conventional cytotoxic salvage chemotherapy in the platinum-refractory setting. Pembrolizumab has the highest level of evidence in platinum-refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of evidence in the frontline setting in cisplatin-ineligible patients. Ongoing research is evaluating novel agents, various rational combinations, and sequences, as well as predictive and prognostic biomarkers.

Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study.

PubMed

Martínez, Carmen; Solano, Carlos; Ferrá, Christelle; Sampol, Antonia; Valcárcel, David; Pérez-Simón, José Antonio

2009-05-01

We conducted a phase II trial to investigate the safety and efficacy of alemtuzumab in treating steroid-refractory acute graft-versus-host disease (aGVHD) grade II or higher after stem cell transplantation. Ten adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with complete response and 3 with partial response. Eight infectious events (4 of grade 3-4) and 7 cytomegalovirus (CMV) reactivations were observed. Six patients had grade 3-4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range, 4 to 88 days) after alemtuzumab treatment. Overall, our findings suggest that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

Successful treatment of generalized refractory chronic periodontitis through discontinuation of waxed or coated dental floss use: A report of 4 cases.

PubMed

Kelekis-Cholakis, Anastasia; Perry, John B; Pfeffer, Lorraine; Millete, Amy

2016-12-01

Generalized refractory chronic periodontitis is a periodontal condition that is resistant to conventional therapy. Management of this condition often is frustrating to both the patient and the clinician. The authors present 4 cases of generalized refractory chronic periodontitis characterized by an inflammatory gingival response and progressive bone loss that did not respond to extensive periodontal treatments and regular periodontal care. Histologic examination of affected gingival tissue revealed an abundance of plasma cells, a feature seen in certain oral contact hypersensitivity reactions. The authors suspected that waxed or coated dental floss was the offending contactant, and its removal from the patients' oral hygiene regimens resulted in a dramatic improvement of the periodontal characteristics. In cases of periodontal disease as described in this report, dental practitioners should consider the possibility of a contact hypersensitivity reaction to waxed or coated dental floss, whereby the floss exacerbates the condition instead of assisting in its resolution. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo

PubMed Central

Cufí, Sílvia; Bonavia, Rosa; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; Martin-Castillo, Begoña; Barrajón-Catalán, Enrique; Visa, Joana; Segura-Carretero, Antonio; Joven, Jorge; Bosch-Barrera, Joaquim; Micol, Vicente; Menendez, Javier A.

2013-01-01

The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21/low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment. PMID:23963283

Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center

PubMed Central

Gibb, Adam; Jones, Craig; Bloor, Adrian; Kulkarni, Samar; Illidge, Tim; Linton, Kim; Radford, John

2013-01-01

The CD30-targeted agent brentuximab vedotin has shown impressive activity in relapsed/refractory Hodgkin lymphoma and anaplastic large cell lymphoma in phase II studies. We have treated 24 patients with relapsed/refratory disease enrolled onto a Named Patient Programme during 2010-11 at a single UK center. Overall response rate across all histologies was 67% (Hodgkin 72%; anaplastic large cell 60%), complete response rate 25% (Hodgkin 17%; anaplastic large cell 60%), median progression-free survival 5.1 months, and toxicity mild to moderate in the majority of cases. Six patients proceeded to allogeneic transplantation and one patient awaits this procedure. These results are similar to phase II data and show that brentuximab vedotin provides a bridge to allogeneic transplantation in approximately one quarter of patients refractory to conventional salvage therapies. Best response was seen after four doses, so consideration of allogeneic transplantation should be made early and scheduled following the first assessment indicating response. PMID:23065511

A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL)

PubMed Central

Spurgeon, Stephen E.; Furman, Richard R.; Flinn, Ian W.; Coutre, Steven E.; Brown, Jennifer R.; Benson, Don M.; Byrd, John C.; Peterman, Sissy; Cho, Yoonjin; Yu, Albert; Godfrey, Wayne R.; Wagner-Johnston, Nina D.

2014-01-01

Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase δ (PI3Kδ), was evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 40 patients with relapsed or refractory mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (range, 52-83) and received median of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Common grade ≥3 adverse events (AEs) included (total%/grade ≥3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3Kδ is a viable strategy and worthy of additional study in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528. PMID:24615778

Measurement of the complex refractive index and complex dielectric permittivity of T.P.S. Space Shuttle tile materials at millimeter wavelengths

NASA Technical Reports Server (NTRS)

Afsar, Mohammed Nurul; Chi, Hua; Li, Xiaohui

1990-01-01

Complex refractive index and dielectric permittivity studies of presently used Space Shuttle tile materials at millimeter wavelengths reveal these tiles to exhibit similar absorption characteristics to those of fused silica materials. This absorption is mainly related to the water content in the specimen. A strong birefringence is observed at least in one of these fibrous refractory composite materials.

77 FR 14569 - Notice of Intent To Grant Exclusive License

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... Direct Chip Attach Packaging Methodologies and Apparatuses for Harsh Environments, LEW 17,256-1, to... equipment; semiconductor manufacturing; material manufacturing such as metallurgy, refractory processes, and...

Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart.

PubMed

Osadchii, O E; Olesen, S P

2009-12-01

Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Hypokalaemic perfusion (2.5 mm K(+) for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD(90) and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart.

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

PubMed

Koenigsmann, M; Casper, J; Kahl, C; Basara, N; Sayer, H G; Behre, G; Theurich, S; Christopeit, M; Mohren, M; Reichle, A; Metzner, B; Ganser, A; Stadler, M; Uharek, L; Balleisen, L; Hinke, A; Hinke, R; Niederwieser, D

2014-03-01

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

ClinicalTrials.gov

2014-04-28

Accelerated Phase Chronic Myelogenous Leukemia; Acute Leukemias of Ambiguous Lineage; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Aggressive NK-cell Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Noncutaneous Extranodal Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma

PubMed Central

Dudley, Mark E.; Wunderlich, John R.; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Royal, Richard E.; Kammula, Udai; White, Don E.; Mavroukakis, Sharon A.; Rogers, Linda J.; Gracia, Gerald J.; Jones, Stephanie A.; Mangiameli, David P.; Pelletier, Michelle M.; Gea-Banacloche, Juan; Robinson, Michael R.; Berman, David M.; Filie, Armando C.; Abati, Andrea; Rosenberg, Steven A.

2006-01-01

Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. PMID:15800326

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

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

Rimner, Andreas; Lovie, Shona; Hsu, Meier

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followedmore » by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.« less

Transpiration-Cooled Spacecraft-Insulation-Repair Fasteners

NASA Technical Reports Server (NTRS)

Camarda, Charles J.; Pettit, Donald R.; Glass, David; Scotti, Stephen J.; Vaughn, Wallace Lee; Rawal, Suraj

2012-01-01

Transpiration-cooled fasteners are proposed that operate like an open-loop heat pipe (self-tapping screws, bolts, and spikes) for use in on-orbit repair of thermal- insulation of a space shuttle or other spacecraft. By limiting the temperature rise of such a fastener and of the adjacent repair material and thermal protection system, the transpiration cooling would contribute to the ability of the repair to retain its strength and integrity in the high-heat-flux, oxidizing environment of reentry into the atmosphere of the Earth. A typical fastener according to the proposal would include a hollow refractory-metal, refractory-composite, or ceramic screw or bolt, the central cavity of which would be occupied by a porous refractory- metal or ceramic plug that would act as both a reservoir and a wick for a transpirant liquid. The plug dimensions, the plug material, and the sizes of the pores would be chosen in conjunction with the transpirant liquid so that (1) capillary pumping could be relied upon to transport the liquid to the heated surface, where the liquid would be vaporized, and (2) the amount of liquid would suffice for protecting against the anticipated heat flux and integrated heat load.

Non-Contact Tabletop Mechanical Testing of Ultra-High Temperature Ceramics

DTIC Science & Technology

2012-05-01

class of refractory materials including transition metal borides , carbides and nitrides e.g. ZrB2l HfB2) ZrC, HfC, TaC, HfN and ZrN. They recently...ike oxidizing atmospheres, at very high temperatures Refractory borides like ZrB2 and HfB2 have extremely high melting temperatures (over 3000°C...But borides are very poor in oxidation resistance, due to the nature of thär oxides Non-protective ZrCfe or Hf02 and volatile liquid B203. Addition

Low resistance barrier layer for isolating, adhering, and passivating copper metal in semiconductor fabrication

DOEpatents

Weihs, Timothy P.; Barbee, Jr., Troy W.

2002-01-01

Cubic or metastable cubic refractory metal carbides act as barrier layers to isolate, adhere, and passivate copper in semiconductor fabrication. One or more barrier layers of the metal carbide are deposited in conjunction with copper metallizations to form a multilayer characterized by a cubic crystal structure with a strong (100) texture. Suitable barrier layer materials include refractory transition metal carbides such as vanadium carbide (VC), niobium carbide (NbC), tantalum carbide (TaC), chromium carbide (Cr.sub.3 C.sub.2), tungsten carbide (WC), and molybdenum carbide (MoC).

Microstructure and Elevated Temperature Properties of a Refractory TaNbHfZrTi Alloy

DTIC Science & Technology

2012-01-24

composition of the TaNbHfZrTi alloy produced by vacuum arc melting Composition Ta Nb Hf Zr Ti at.% 19.68 18.93 20.46 21.23 19.7 wt. % 30.04 14.84 30.82 16.34...metallic materials with higher melting points, such as refractory molybdenum (Mo) and niobium ( Nb ) alloys, are examined as alternatives by academic and...creep resistance are the key properties of these alloys, since considerable alloy softening generally occurs at tempera- tures above *0.5 0.6 Tm

Vertical feed stick wood fuel burning furnace system

DOEpatents

Hill, Richard C.

1982-01-01

A stove or furnace for efficient combustion of wood fuel includes a vertical feed combustion chamber (15) for receiving and supporting wood fuel in a vertical attitude or stack. A major upper portion of the combustion chamber column comprises a water jacket (14) for coupling to a source of water or heat transfer fluid for convection circulation of the fluid. The locus (31) of wood fuel combustion is thereby confined to the refractory base of the combustion chamber. A flue gas propagation delay channel (34) extending laterally from the base of the chamber affords delayed travel time in a high temperature refractory environment sufficient to assure substantially complete combustion of the gaseous products of wood burning with forced air prior to extraction of heat in heat exchanger (16). Induced draft draws the fuel gas and air mixture laterally through the combustion chamber and refractory high temperature zone to the heat exchanger and flue. Also included are active sources of forced air and induced draft, multiple circuit couplings for the recovered heat, and construction features in the refractory material substructure and metal component superstructure.

Estimation of sensing characteristics for refractory nitrides based gain assisted core-shell plasmonic nanoparticles

NASA Astrophysics Data System (ADS)

Shishodia, Manmohan Singh; Pathania, Pankaj

2018-04-01

Refractory transition metal nitrides such as zirconium nitride (ZrN), hafnium nitride (HfN) and titanium nitride (TiN) have emerged as viable alternatives to coinage metals based plasmonic materials, e.g., gold (Au) and silver (Ag). The present work assesses the suitability of gain assisted ZrN-, HfN- and TiN-based conventional core-shell nanoparticles (CCSNPs) and multilayered core-shell nanoparticles (MCSNPs) for refractive index sensing. We report that the optical gain incorporation in the dielectric layer leads to multifold enhancement of the scattering efficiency (Qsca), substantial reduction of the spectral full width at half maximum, and a higher figure of merit (FOM). In comparison with CCSNPs, the MCSNP system exhibits superior sensing characteristics such as higher FOM, ˜ 45% reduction in the critical optical gain, response shift towards the biological window, and higher degree of tunability. Inherent biocompatibility, growth compatibility, chemical stability and flexible spectral tuning of refractory nitrides augmented by superior sensing properties in the present work may pave the way for refractory nitrides based low cost sensing.

Etude de la degradation des refractaires aluminosiliceux par abrasion, chocs thermiques et corrosion par l'aluminium: Correlation et interaction des mecanismes

NASA Astrophysics Data System (ADS)

Ntakaburimvo, Nicodeme

Aluminosilicate refractories used for melting and holding furnaces on which the present work was focused are submitted to mechanical abuse such as abrasion, mechanical impact and erosion, on one hand; and to chemical degradation by corrosion, as well as to thermal stresses, mostly due to thermal shocks; on the other hand. This thesis is focused on four main objectives. The first one is related to the designing of an experimental set-up allowing abrasion testing of refractories. The second deals with the separate study of the deterioration of aluminosilicate refractories by abrasion, thermal shock and corrosion. The third is the correlation between these three mechanisms while the fourth is related to the interaction between thermal shock and corrosion. One of the contributions of this thesis is the realisation of the above mentioned experimental set-up, which permits to carry out refractories abrasion testing, as well as at room and high temperature, in the absence or in the presence of molten metal. The fact of testing refractory resistance when it is submitted separately and simultaneously to the action of dynamic corrosion, erosion and abrasion leads to the studying of the influence of each of these three mechanisms on the other. One of the characteristics of the designed set-up is the fact that it allows to adjust the seventy testing conditions according to the mechanical resistance of the test material. The other important point is related to the fact the abrasion tests were carried out in such manner to permit degradation quantification, otherwise than by the traditional method of loss of weight measurement; particularly by measuring the wear depth and the residual material properties, such as the rupture force and the strength. A perfect correlation was observed between the wear depth and the loss of weight, both being negatively correlated with the residual rupture force. The abrasion resistance was found to be globally positively correlated with the original mechanical material's properties such as the modulus of rupture, the toughness and the elastic modulus. However, for same mechanical resistance for bricks and castables, the latter were more degraded because of more microstructural defects they contain. Moreover, in case of the castables, the original surface facing the mould was more abraded than a rectified surface because of the segregation phenomenon. It has been shown in this study that the abrasion process has no longer effect on material's strength unless the cracks length it promotes is higher than that of the initial defects. (Abstract shortened by UMI.)

Transcription factor Stat5a/b as a therapeutic target protein for prostate cancer

PubMed Central

Liao, Zhiyong; Lutz, Jacqueline; Nevalainen, Marja T.

2009-01-01

Prostate cancer is the most common non-cutaneous cancer in Western males. The majority of prostate cancer fatalities are caused by development of castration-resistant growth and metastatic spread of the primary tumor. The average duration of the response of primary prostate cancer to hormonal ablation is less than 3 years, and 75% of prostate cancers in the United States progress to hormone-refractory disease. The existing pharmacological therapies for metastatic and/or hormone-refractory prostate cancer do not provide significant survival benefit. This review summarizes the importance of transcription factor Stat5 signaling in the pathogenesis of prostate cancer and discusses the molecular basis why inhibition of Stat5a/b could be used as a therapeutic strategy for prostate cancer. PMID:19914392

Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

PubMed Central

Mermelstein, Joseph; Chait Mermelstein, Alanna; Chait, Maxwell M

2018-01-01

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. PMID:29606884

The GHSG Approach to Treating Hodgkin's Lymphoma.

PubMed

Bröckelmann, Paul J; Engert, Andreas

2015-09-01

Hodgkin's lymphoma (HL) is a relatively rare disease accounting for 15 % of all lymphoma. This disease has developed from an incurable disease to the adult malignancy with the most favorable prognosis. With current therapeutic approaches consisting of polychemo- and small-field radiotherapy, up to 80 % of all patients can be cured long term. In refractory or relapsed HL, intensified treatment including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is associated with progression-free survival (PFS) of 50 %. Evaluation of novel drugs in multiple relapsed or refractory cases, better treatment options for elderly patients and reducing treatment-related side effects are the main focus of current research. Recent clinical developments and future approaches in the treatment of HL will be discussed in this review.

40 CFR 98.460 - Definition of the source category.

Code of Federal Regulations, 2011 CFR

2011-07-01

... cull. (viii) Bricks, mortar, or cement. (ix) Furnace slag. (x) Materials used as refractory (e.g., alumina, silicon, fire clay, fire brick). (xi) Plastics (e.g., polyethylene, polypropylene, polyethylene...

Device for hydrogen separation and method

DOEpatents

Paglieri, Stephen N [White Rock, NM; Anderson, Iver E [Ames, IA; Terpstra, Robert L [Ames, IA

2009-11-03

A device for hydrogen separation has a porous support and hydrogen separation material on the support. The support is prepared by heat treatment of metal microparticles, preferably of iron-based or nickel-based alloys that also include aluminum and/or yttrium. The hydrogen separation material is then deposited on the support. Preferred hydrogen separation materials include metals such as palladium, alloys, platinum, refractory metals, and alloys.

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

Ellingson, W.A.

This broad-base materials engineering program, begun in October 1974, includes studies on both ceramic (refractory) and metallic materials presently being used or intended for use in coal-conversion systems. Appropriate laboratory and field experiments are integrated such that the results have immediate impact on the present pilot-plant and proposed demonstration-plant designs. The report presents the technical accomplishments.

Fabrication of smooth patterned structures of refractory metals, semiconductors, and oxides via template stripping.

PubMed

Park, Jong Hyuk; Nagpal, Prashant; McPeak, Kevin M; Lindquist, Nathan C; Oh, Sang-Hyun; Norris, David J

2013-10-09

The template-stripping method can yield smooth patterned films without surface contamination. However, the process is typically limited to coinage metals such as silver and gold because other materials cannot be readily stripped from silicon templates due to strong adhesion. Herein, we report a more general template-stripping method that is applicable to a larger variety of materials, including refractory metals, semiconductors, and oxides. To address the adhesion issue, we introduce a thin gold layer between the template and the deposited materials. After peeling off the combined film from the template, the gold layer can be selectively removed via wet etching to reveal a smooth patterned structure of the desired material. Further, we demonstrate template-stripped multilayer structures that have potential applications for photovoltaics and solar absorbers. An entire patterned device, which can include a transparent conductor, semiconductor absorber, and back contact, can be fabricated. Since our approach can also produce many copies of the patterned structure with high fidelity by reusing the template, a low-cost and high-throughput process in micro- and nanofabrication is provided that is useful for electronics, plasmonics, and nanophotonics.

Initial Assessment of Environmental Barrier Coatings for the Prometheus Project

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

M. Frederick

2005-12-15

Depending upon final design and materials selections, a variety of engineering solutions may need to be considered to avoid chemical degradation of components in a notional space nuclear power plant (SNPP). Coatings are one engineered approach that was considered. A comprehensive review of protective coating technology for various space-reactor structural materials is presented, including refractory metal alloys [molybdenum (Mo), tungsten (W), rhenium (Re), tantalum (Ta), and niobium (Nb)], nickel (Ni)-base superalloys, and silicon carbide (Sic). A summary description of some common deposition techniques is included. A literature survey identified coatings based on silicides or iridium/rhenium as the primary methods formore » environmental protection of refractory metal alloys. Modified aluminide coatings have been identified for superalloys and multilayer ceramic coatings for protection of Sic. All reviewed research focused on protecting structural materials from extreme temperatures in highly oxidizing conditions. Thermodynamic analyses indicate that some of these coatings may not be protective in the high-temperature, impure-He environment expected in a Prometheus reactor system. Further research is proposed to determine extensibility of these coating materials to less-oxidizing or neutral environments.« less

Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM.

PubMed

Moreau, Philippe; Chanan-Khan, Asher; Roberts, Andrew W; Agarwal, Amit B; Facon, Thierry; Kumar, Shaji; Touzeau, Cyrille; Punnoose, Elizabeth A; Cordero, Jaclyn; Munasinghe, Wijith; Jia, Jia; Salem, Ahmed Hamed; Freise, Kevin J; Leverson, Joel D; Enschede, Sari Heitner; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Harrison, Simon J

2017-11-30

The antiapoptotic proteins BCL-2 and myeloid cell leukemia sequence 1 (MCL-1) promote multiple myeloma (MM) cell survival. Venetoclax is a selective, orally bioavailable small-molecule BCL-2 inhibitor; bortezomib can indirectly inhibit MCL-1. In preclinical studies, venetoclax enhanced bortezomib activity, suggesting that cotargeting of BCL-2 and MCL-1 could be an effective treatment strategy in myeloma. This phase 1b trial studied patients with relapsed/refractory MM receiving daily venetoclax (50-1200 mg per designated dose cohort; 800 mg in safety expansion) in combination with bortezomib and dexamethasone. A total of 66 patients were enrolled (54 in the dose-escalation cohorts and 12 in the safety expansion). Patients had received a median of 3 prior therapies (range, 1-13); 26 (39%) were refractory to prior bortezomib and 35 (53%) to lenalidomide; 39 (59%) had prior stem cell transplant. The combination was generally well tolerated, and common adverse events included mild gastrointestinal toxicities (diarrhea [46%], constipation [41%], and nausea [38%]) and grade 3/4 cytopenias (thrombocytopenia [29%] and anemia [15%]). The overall response rate (ORR) was 67% (44/66); 42% achieved very good partial response or better (≥VGPR). Median time to progression and duration of response were 9.5 and 9.7 months, respectively. ORR of 97% and ≥VGPR 73% were seen in patients not refractory to bortezomib who had 1 to 3 prior therapies. Patients with high BCL2 expression had a higher ORR (94% [17/18]) than patients with low BCL2 expression (59% [16/27]). This novel combination of venetoclax with bortezomib and dexamethasone has an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM. This trial was registered at www.clinicaltrials.gov as #NCT01794507. © 2017 by The American Society of Hematology.

Distributed Fiber Optic Sensor for On-Line Monitoring of Coal Gasifier Refractory Health

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

Wang, Anbo; Yu, Zhihao

This report summarizes technical progress on the program “Distributed Fiber Optic Sensor for On-Line Monitoring of Coal Gasifier Refractory Health,” funded by the National Energy Technology Laboratory of the U.S. Department of Energy, and performed by the Center for Photonics Technology of the Bradley Department of Electrical and Computer Engineering at Virginia Tech. The scope of work entails analyses of traveling grating generation technologies in an optical fiber, as well as the interrogation of the gratings to infer a distributed temperature along the fiber, for the purpose of developing a real-time refractory health condition monitoring technology for coal gasifiers. Duringmore » the project period, which is from 2011-2015, three different sensing principles were studied, including four-wave mixing (FWM), coherent optical time-domain reflectometer (C-OTDR) and Brillouin optical time-domain analysis (BOTDA). By comparing the three methods, the BOTDA was selected for further development into a complete bench-top sensing system for the proposed high-temperature sensing application. Based on the input from Eastman Chemical, the industrial collaborator on this project, a cylindrical furnace was designed and constructed to simulate typical gasifier refractory temperature conditions in the laboratory, and verify the sensor’s capability to fully monitor refractory conditions on the back-side at temperatures up to 1000°C. In the later stages of the project, the sensing system was tested in the simulated environment for its sensing performance and high-temperature survivability. Through theoretical analyses and experimental research on the different factors affecting the sensor performance, a sensor field deployment strategy was proposed for possible future sensor field implementations.« less

Survivin as prognostic and predictive factor in patients treated with gemcitabine, dexamethasone, and cisplatin for relapsed or refractory aggressive NHL.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-11-01

The prognosis of relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Survivin is a member of the family of inhibitors of apoptosis, and survivin was associated with short survival and bad prognosis. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone and cisplatin) on relapsed or refractory aggressive NHL and various prognostic factors with special emphasis on survivin and observe the . Forty-six patients with relapsed and refractory NHL, intermediate or high-grade NHL (Revised European American Lymphoma Classification), who at least one regimen were enrolled into this study, which was carried out at Department, , Tanta University from July 2012 to July 2014. The patients were treated with GDP regimen (gemcitabine 1,000 mg/m(2) on days one and eight, dexamethasone 40 mg on days 1-3, and cisplatin 25 mg/m(2) on days 1-3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. All patients were assessed for efficacy and toxicity. The overall response rate was 58.7 %. Fourteen patients showed a complete response, thirteen partial responses, twelve stable diseases, and seven progressive disease. The 24-month overall survival was 50.8 %. Survivin is associated with low overall response and shorter overall survival. Grade 3 anemia was observed in four patients, grade 3 leucopenia in six patients, grade 3 neutropenia in six patients, and grade 3 thrombocytopenia in four patients. Non-hematologic toxicity included grade 3 infection in four patients. The present schedule of GDP showed modest efficacy and mild toxicity in patients with relapsed or refractory aggressive NHL.

Demonstration of a stabilized alumina/ethanol colloidal dispersion technique for seeding high temperature air flows

NASA Technical Reports Server (NTRS)

Wernet, Mark P.; Skoch, Gary J.; Wernet, Judith H.

1995-01-01

Laser anemometry enables the measurement of complex flow fields via the light scattered from small particles entrained in the flow. In the study of turbomachinery, refractory seed materials are required for seeding the flow due to the high temperatures encountered. In this work we present a pH stabilization technique commonly employed in ceramic processing to obtain stable dispersions for generating aerosols of refractory seed material. By adding submicron alumina particles to a preadjusted pH solution of ethanol, a stable dispersion is obtained which when atomized, produces a high quality aerosol. Commercial grade alumina powder is used with a moderate size distribution. Other metal oxide powders in various polar solvents could also be used once the point of zero charge (pH(pzc)) of the powder in the solvent has been determined. Laser anemometry measurements obtained using the new seeding technique are compared to measurements obtained using Polystyrene Latex (PSL) spheres as the seed material.

Moving Bed Granular Bed Filter Development Program. Topical report, September 1994

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

Haas, J.C.; Prudhomme, J.W.; Wilson, K.W.

1994-09-01

Five test arrangements have been designed to support the Granular Bed Filter Development Program as defined in the Test Plan. The first arrangement is a 3.6 ft. diameter half filter, with a glass covering along the cross section to allow visual examination of the granular alumina material passing through the filter. The second test arrangement is a 3.6 ft diameter full size filter having refractory lining to simulate actual surface roughness conditions. The third test arrangement will examine filter geometry scale up by testing a 6.0 ft. diameter full size filter. The fourth Test Arrangement consists of a small 12more » inch diameter fluidizer to measure the minimum fluidization velocity of the 7 m (approx. size) alumina material to be used in the filter assemblies. The last Test Unit is used to evaluation relative abrasion characteristics of potential refractory and ceramic materials to be installed in high abrasion areas in the pneumatic transport piping.« less

Laser welding of fused quartz

DOEpatents

Piltch, Martin S.; Carpenter, Robert W.; Archer, III, McIlwaine

2003-06-10

Refractory materials, such as fused quartz plates and rods are welded using a heat source, such as a high power continuous wave carbon dioxide laser. The radiation is optimized through a process of varying the power, the focus, and the feed rates of the laser such that full penetration welds may be accomplished. The process of optimization varies the characteristic wavelengths of the laser until the radiation is almost completely absorbed by the refractory material, thereby leading to a very rapid heating of the material to the melting point. This optimization naturally occurs when a carbon dioxide laser is used to weld quartz. As such this method of quartz welding creates a minimum sized heat-affected zone. Furthermore, the welding apparatus and process requires a ventilation system to carry away the silicon oxides that are produced during the welding process to avoid the deposition of the silicon oxides on the surface of the quartz plates or the contamination of the welds with the silicon oxides.

Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

PubMed Central

Patel, Jesal C.; Maughan, Benjamin L.; Agarwal, Archana M.; Batten, Julia A.; Zhang, Tian Y.; Agarwal, Neeraj

2013-01-01

Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials. PMID:23819055

Veno-arterial extracorporeal membrane oxygenation for Streptococcus pyogenes toxic shock syndrome in pregnancy.

PubMed

Imaeda, Taro; Nakada, Taka-Aki; Abe, Ryuzo; Tateishi, Yoshihisa; Oda, Shigeto

2016-06-01

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS.

Emergence of Persistent Infection due to Heterogeneity

NASA Astrophysics Data System (ADS)

Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

2017-02-01

We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.

PubMed

Walker, Melissa A; Mohler, Kyle P; Hopkins, Kyle W; Oakley, Derek H; Sweetser, David A; Ibba, Michael; Frosch, Matthew P; Thibert, Ronald L

2016-08-01

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins. © The Author(s) 2016.

A messenger at the door: cytomegalovirus retinitis in myeloma patients with progressive disease.

PubMed

Teh, B W; Khot, A S; Harrison, S J; Prince, H M; Slavin, M A

2013-08-01

Cytomegalovirus (CMV) retinitis is an uncommon manifestation of CMV disease and is a marker of severe and profound immunosuppression in human immunodeficiency virus-positive patients. Here, we describe 2 cases of CMV retinitis in myeloma patients with progressive disease, following autologous stem cell transplantation and immunomodulatory therapy for myeloma. To our knowledge, this is the first report of CMV retinitis in this patient population. This report illustrates the need for close monitoring of relapsed and refractory myeloma patients for new presentations of opportunistic infections secondary to severe immunosuppression. © 2013 John Wiley & Sons A/S.

High temperature barrier coatings for refractory metals

NASA Technical Reports Server (NTRS)

Malone, G. A.; Walech, T.

1995-01-01

Improvements in high temperature oxidation resistant metal coating technology will allow NASA and commercial entities to develop competitive civil space transport and communication systems. The success of investigations completed in this program will have a positive impact on broadening the technology base for high temperature materials. The work reported herein describes processes and procedures for successfully depositing coherent oxidation barrier coatings on refractory metals to prevent degradation under very severe operating environments. Application of the new technology developed is now being utilized in numerous Phase 3 applications through several prominent aerospace firms. Major achievements have included: (1) development of means to deposit thick platinum and rhodium coatings with lower stress and fewer microcracks than could be previously achieved; (2) development of processes to deposit thick adherent coatings of platinum group metals on refractory substrates that remain bonded through high temperature excursions and without need for intermediate coatings (bonding processes unique to specific refractory metals and alloys have been defined; (3) demonstration that useful alloys of refractory and platinum coatings can be made through thermal diffusion means; (4) demonstration that selected barrier coatings on refractory substrates can withstand severe oxidizing environments in the range of 1260 deg and 1760 deg C for long time periods essential to the life requirements of the hardware; and (5) successful application of the processes and procedures to prototype hardware. The results of these studies have been instrumental in improved thermal oxidation barrier coatings for the NASP propulsion system. Other Phase 3 applications currently being exploited include small uncooled thrusters for spacecraft and microsatellite maneuvering systems.

NASA research on refractory compounds.

NASA Technical Reports Server (NTRS)

Gangler, J. J.

1971-01-01

The behavior and properties of the refractory carbides, nitrides, and borides are being investigated by NASA as part of its research aimed at developing superior heat resistant materials for aerospace applications. Fundamental studies on the electronic and defect structures of the carbides indicate that there is promise for improving the strength and ductility of these materials. Studies of the zirconium-carbon-oxygen system show that zirconium oxycarbides of different compositions and lattice parameters can be formed between 1500 and 1900 C and are stable below 1500 C. More applied studies show that hot working generally improves the microstructure and therefore the strength of TiC and NbC. Sintering studies on UN indicate that very high densities can be achieved. Hot pressing of cermets of HfN and HfC produces good mechanical properties for high temperature bearing applications.

Ice chemistry on outer solar system bodies: Carboxylic acids, nitriles, and urea detected in refractory residues produced from the UV photolysis of N{sub 2}:CH{sub 4}:CO-containing ices

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

Materese, Christopher K.; Cruikshank, Dale P.; Sandford, Scott A.

Radiation processing of the surface ices of outer solar system bodies may result in the production of new chemical species even at low temperatures. Many of the smaller, more volatile molecules that are likely produced by the photolysis of these ices have been well characterized by laboratory experiments. However, the more complex refractory material formed in these experiments remains largely uncharacterized. In this work, we present a series of laboratory experiments in which low-temperature (15-20 K) N{sub 2}:CH{sub 4}:CO ices in relative proportions 100:1:1 are subjected to UV irradiation, and the resulting materials are studied with a variety of analyticalmore » techniques including infrared spectroscopy, X-ray absorption near-edge structure spectroscopy, gas chromatography coupled with mass spectrometry, and high-resolution mass spectroscopy. Despite the simplicity of the reactants, these experiments result in the production of a highly complex mixture of molecules from relatively low-mass volatiles (tens of daltons) to high-mass refractory materials (hundreds of daltons). These products include various carboxylic acids, nitriles, and urea, which are also expected to be present on the surface of outer solar system bodies, including Pluto and other transneptunian objects. If these compounds occur in sufficient concentrations in the ices of outer solar system bodies, their characteristic bands may be detectable in the near-infrared spectra of these objects.« less

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

PubMed

Beköz, H; Karadurmus, N; Paydas, S; Türker, A; Toptas, T; Firatli Tuglular, T; Sönmez, M; Gülbas, Z; Tekgündüz, E; Kaya, A H; Özbalak, M; Tastemir, N; Kaynar, L; Yildirim, R; Karadogan, I; Arat, M; Pepedil Tanrikulu, F; Özkocaman, V; Abali, H; Turgut, M; Kurt Yüksel, M; Özcan, M; Dogu, M H; Kabukçu Hacioglu, S; Barista, I; Demirkaya, M; Köseoglu, F D; Toprak, S K; Yilmaz, M; Demirkürek, H C; Demirkol, O; Ferhanoglu, B

2017-10-01

Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

PubMed

Zhong, Dong Ta; Shi, Chun Mei; Chen, Qiang; Huang, Jing Ze; Liang, Jian Gang

2012-11-01

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1% (95% confidence interval, CI, 40.1-68.3%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8% (95% CI 58.0-83.7%), and the 5-year OS was 41.7% (95% CI 27.7-55.6%). The 2-year progression-free survival rate (PFS) was 37.5% (95% CI 23.8-51.2%), and the 5-year PFS was 25.0% (95% CI 12.8-37.3%). The median progression-free survival was 8.8 months (95% CI 0-20.3 months), and the median overall survival was 40.6 months (95% CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3%; leukopenia, 37.5%; and thrombocytopenia, 48.3%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study.

PubMed

Palanca-Wessels, Maria Corinna A; Czuczman, Myron; Salles, Gilles; Assouline, Sarit; Sehn, Laurie H; Flinn, Ian; Patel, Manish R; Sangha, Randeep; Hagenbeek, Anton; Advani, Ranjana; Tilly, Herve; Casasnovas, Olivier; Press, Oliver W; Yalamanchili, Sreeni; Kahn, Robert; Dere, Randall C; Lu, Dan; Jones, Surai; Jones, Cheryl; Chu, Yu-Waye; Morschhauser, Franck

2015-06-01

Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1-2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m(2). Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov, number NCT01290549. Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of activity in the dose-escalation cohort). The recommended phase 2 dose in NHL was 2·4 mg/kg as a single agent and in combination with rituximab; the maximum tolerated dose in CLL was 1·0 mg/kg as a result of dose-limiting toxic effects reported in two of five patients given 1·8 mg/kg. Grade 3-4 adverse events were reported in 26 (58%) of 45 patients with NHL treated at the single-agent recommended phase 2 dose, and the most common grade 3-4 adverse events were neutropenia (18 [40%] of 45), anaemia (five [11%]), and peripheral sensory neuropathy (four [9%]). Serious adverse events were reported in 17 (38%) of 45 patients, and included diarrhoea (two patients), lung infection (two patients), disease progression (two patients), and lung disorder (two patients). Seven (77%) of nine patients in the rituximab combination cohort had a grade 3-4 adverse event, with neutropenia (five [56%]), anaemia (two [22%]), and febrile neutropenia (two [22%]) reported in more than one patient. 11 (12%) of 95 patients died during the study: eight with relapsed or refractory diffuse large B-cell lymphoma (due to progressive disease in four patients, infections in three patients [two treatment related], and treatment-related worsening ascites in one patient) and three with relapsed or refractory CLL (due to progressive disease, pulmonary infection, and pneumonia; none thought to be treatment-related). At the recommended phase 2 dose, objective responses were noted in 23 of 42 activity-evaluable patients with NHL given single-agent polatuzumab vedotin (14 of 25 with diffuse large B-cell lymphoma, seven of 15 with indolent NHL, and two with mantle-cell lymphoma) and seven of nine patients treated with polatuzumab vedotin combined with rituximab. No objective responses were observed in patients with CLL. Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further assessed in NHL. Genentech. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical Characteristics of Patients with Gastroesophageal Reflux Disease Refractory to Proton Pump Inhibitors and the Effects of Switching to 20 mg Esomeprazole on Reflux Symptoms and Quality of Life

PubMed Central

Takeshima, Fuminao; Hashiguchi, Keiichi; Onitsuka, Yasunori; Tanigawa, Ken; Minami, Hitomi; Matsushima, Kayoko; Akazawa, Yuko; Shiozawa, Ken; Yamaguchi, Naoyuki; Taura, Naota; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2015-01-01

Background Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. Material/Methods Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. Results Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged ≥65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, abdominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. Conclusions About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symptoms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL. PMID:26719012

Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma.

PubMed

Illhardt, Toni; Toporski, Jacek; Feuchtinger, Tobias; Turkiewicz, Dominik; Teltschik, Heiko-Manuel; Ebinger, Martin; Schwarze, Carl-Philipp; Holzer, Ursula; Lode, Holger N; Albert, Michael H; Gruhn, Bernd; Urban, Christian; Dykes, Josefina H; Teuffel, Oliver; Schumm, Michael; Handgretinger, Rupert; Lang, Peter

2018-05-01

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 10 6 /kg T/B cell-depleted CD34 + stem cells with 68 × 10 3 /kg residual T cells and 107 × 10 6 /kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system. Copyright © 2018. Published by Elsevier Inc.

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

PubMed

Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Hayashi, Katsuhiro; Yamamoto, Norio; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

2017-05-01

There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society. © 2017 American Cancer Society.

Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

PubMed

Zschäbitz, Stefanie; Distler, Florian A; Krieger, Benjamin; Wuchter, Patrick; Schäfer-Eckart, Kerstin; Jenzer, Maximilian; Hohenfellner, Markus; Dreger, Peter; Haag, Georg Martin; Jäger, Dirk; Pahernik, Sascha; Grüllich, Carsten

2018-04-27

Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities. Most patients were classified as poor risk according to IGCCCG ( n = 24; 52%) and as intermediate ( n = 12), high ( n = 16), or very high risk ( n = 9) at time of first relapse according to IPFSG criteria. In 67% of patients ( n = 31) HDCT/ASCT was performed as first salvage treatment in relapse or for primary refractory disease following first line chemotherapy. In 46% of patients ( n = 21) progressive disease was documented after mobilization and prior to HDCT/ASCT. Median progression free survival (mPFS) was 7.4 months (95% confidence interval (CI): 1.3-13.6) while median overall survival (mOS) was 22.2 months (95% CI: 8.9-35.5). When stratified for IPFSG risk group, mPFS ( p < 0.001) and mOS ( p = 0.009) differed significantly between risk groups (very low vs. low vs. intermediate vs. high vs. very high). Metastases to liver/bone/brain and platinum refractory disease were independent risk factors for inferior PFS ( p = 0.024; p = 0.008) but not OS. Forty-six patients treated with HDCT/ASCT at the university clinics in Heidelberg and Nuremberg between 2000-2016 were identified and analyzed. Data was collected retrospectively. HDCT/ASCT offers a potential curative strategy for patients with relapsed GCT. Improvement is still needed in patients with intermediate, high, and very high IPFSG risk group.

Experimental constraints on heating and cooling rates of refractory inclusions in the early solar system

NASA Technical Reports Server (NTRS)

Boynton, W. V.; DRAKE; HILDEBRAND; JONES; LEWIS; TREIMAN; WARK

1987-01-01

The refractory inclusions in carbonaceous chondrites were the subject of considerable interest since their discovery. These inclusions contain minerals that are predicted to be some of the earliest condensates from the solar nebula, and contain a plethora of isotopic anomalies of unknown origin. Of particular interest are those coarse-grained inclusions that contain refractory metal particles (Fe, Ni, Pt, Ru, Os Ir). Experimental studies of these inclusions in terrestrial laboratories are, however, complicated because the dense particles tend to settle out of a molten or partially molten silicate material. Heating experiments in the Space Station technology and microgravity in order to observe the effects of metal nuggets (which may act as heterogeneous nucleation sites) on nucleation rates in silicate systems and to measure simultaneously the relative volatilization rate of siderophile and lithophile species. Neither experiment is possible in the terrestrial environment.

Constraints on Galactic Cosmic-Ray Origins from Elemental and Isotopic Composition Measurements

NASA Technical Reports Server (NTRS)

Binns, W. R.; Christian, E. R.; Cummings, A. C.; deNolfo, G. A.; Israel, M. H.; Leske, R. A.; Mewaldt, R. A,; Stone, E. C.; vonRosevinge, T. T.; Wiedenbeck, M. E.

2013-01-01

The most recent measurements by the Cosmic Ray Isotope Spectrometer (CRIS) aboard the Advanced Composition Explorer (ACE) satellite of ultra-heavy cosmic ray isotopic and elemental abundances will be presented. A range of isotope and element ratios, most importantly Ne-22/Ne-20, Fe-58/Fe-56, and Ga-31/Ge -32 show that the composition is consistent with source material that is a mix of approx 80% ISM (with Solar System abundances) and 20% outflow/ejecta from massive stars. In addition, our data show that the ordering of refractory and volatile elements with atomic mass is greatly improved when compared to an approx 80%/20% mix rather than pure ISM, that the refractory and volatile elements have similar slopes, and that refractory elements are preferentially accelerated by a factor of approx 4. We conclude that these data are consistent with an OB association origin of GCRs.

Feasibility Study for Casting of High Temperature Refractory Superalloy Composites

NASA Technical Reports Server (NTRS)

Lee, Jonathan A.

1998-01-01

Abstract This study investigated the feasibility of using conventional casting technique to fabricate refractory wires reinforced superalloy composites. These composites were being developed for advanced rocket engine turbine blades and other high temperature applications operating up to 2000 F. Several types of refractory metal wires such as W- Th, W-Re, Mo-Hf-C and W-HF-C reinforced waspaloy were experimentally cast and heat treated at 2000 F up to 48 hrs. Scanning electron microscope analysis was conducted in regions adjacent to the wire-matrix interface to determine the reaction zone and chemical compatibility resulting from material interdiffusion. It was concluded that fabrication using conventional casting may be feasible because the wire-matrix reaction zone thickness was comparable to similar composites produced by arc-sprayed monotape with hot isostatic pressing technique, Moreover, it was also found that the chemical compatibility could be improved significantly through a slight modification of the superalloy matrix compositions.

Production and application of chemical fibers with special properties for manufacturing composite materials and goods of different usage

NASA Technical Reports Server (NTRS)

Levit, R.

1993-01-01

The development of modern technologies demands the creation of new nonmetallic, fibrous materials with specific properties. The fibers and materials developed by NII 'Chimvolokno', St. Petersburg, can be divided into two groups. The first group includes heat-resistant fibers, fire-resistant fibers, thermotropic fibers, fibers for medical application, and textile structures. The second group contains refractory fibers, chemoresistant and antifriction fibers, fibers on the basis of polyvinyl alcohol, microfiltering films, and paperlike and nonwoven materials. In cooperation with NPO 'Chimvolokno' MYTITSHI, we developed and started producing heat-resistant high-strength fibers on the base of polyhetarearilin and aromatic polyimides (SVM and terlon); heat-resistant fibers on the base of polyemede (aramid); fire-retardant fibers (togilen); chemoresistant and antifriction fibers on the basis of homo and copolymers of polytetrafluoroethylene (polyfen and ftorin); and water soluble, acetylated, and high-modulus fibers from polyvinyl alcohol (vylen). Separate reports will deal with textile structures and thermotropic fibers, as well as with medical fibers. One of the groups of refractory fibers carbon fibers (CF) and the corresponding paperlike nonwoven materials are discussed in detail. Also, composite materials (CM) and their base, which is the subject of the author's research since 1968, is discussed.

Ofatumumab for the treatment of chronic lymphocytic leukaemia in patients who are refractory to fludarabine and alemtuzumab: a critique of the submission from GSK.

PubMed

Hoyle, M; Crathorne, L; Garside, R; Hyde, C

2011-05-01

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ofatumumab for the treatment of refractory chronic lymphocytic leukaemia (CLL), based upon the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included one study: a non-randomised, single-arm study. Two other studies were identified but both were non-comparative and provided evidence for therapies other than ofatumumab. For this reason these studies were not discussed in full in the main body of the submission. In the Hx-CD20-406 study, the overall response rate was 58% (99% confidence interval 40% to 74%, p < 0.001). Complete resolution of constitutional symptoms and improved performance status occurred in 57% of patients. Median progression-free survival (PFS) and overall survival (OS) times were 5.7 and 13.7 months, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. The MS concluded that ofatumumab provides a new, effective and well-tolerated therapy for patients with CLL who are refractory to both fludarabine and alemtuzumab [double refractory (DR)]. The ERG undertook a critical appraisal of the submission. The ERG had a number of concerns regarding the manufacturer's estimates of effectiveness based on evidence from a single-arm, non-randomised study. An 'area-under-the-curve' or 'partitioned-survival' model was used to project expected clinical and economic outcomes for patients with DR CLL who were assumed to receive ofatumumab or best supportive care (BSC). The model had a three-state structure: 'alive pre-progression', 'alive post progression' and 'dead'. Overall, the modelling approach is reasonable given the limited evidence available for the drug in the patient population under review. However, a number of uncertainties were identified in the economic evaluation; for example, the BSC arm used data from patients in the Hx-CD20-406 study who did not respond to ofatumumab treatment - 'non-responders' - and the ofatumumab arm used data from all of those treated in the Hx-CD20-406 study. Further uncertainty arose regarding the choice of utilities, the omission of 17p and 11q chromosomal deletions as factors in the Cox proportional hazards models for PFS and OS, and the omission of the costs of drugs in progressive disease. It was felt that these factors biased cost-effectiveness in favour of ofatumumab. When revisions were made to the assumptions in the model based on the ERG's review of the published and submitted evidence, the revised base-case incremental cost-effectiveness ratio for ofatumumab increased to £ 81,500 per quality-adjusted life-year. The final appraisal determination was issued by NICE in September 2010 (www.nice.org.uk/nicemedia/live/12264/50758/50758.pdf).

NEUTRONIC REACTOR

DOEpatents

Daniels, F.

1959-10-27

A reactor in which at least a portion of the moderator is in the form of movable refractory balls is described. In addition to their moderating capacity, these balls may serve as carriers for fissionable material or fertile material, or may serve in a coolant capacity to remove heat from the reactor. A pneumatic system is used to circulate the balls through the reactor.

Development of an external ceramic insulation for the space shuttle orbiter. Part 3: Development of stabilized aluminum phosphate fibers

NASA Technical Reports Server (NTRS)

Ormiston, T.; Tanzilli, R. A.

1973-01-01

The development of reusable surface insulation materials that are thermal shock resistant and highly refractory is discussed. A stabilized, high-cristobalite, aluminum orthophosphate fiber was developed and found to possess the desired qualities. The application of such a material to heat shielding for space shuttles is examined.

Petrographic studies of refractory inclusions from the Murchison meteorite

NASA Technical Reports Server (NTRS)

Macpherson, G. J.; Grossman, L.; Hashimoto, A.; Bar-Matthews, M.; Tanaka, T.

1984-01-01

Textural and mineral-chemical data on freeze-thaw disaggregated refractory inclusions from the Murchison meteorite are reported. The data were obtained with neutron activation analysis, SEM, and spectroscopy, the study revealed corundum-bearing inclusions, spinel-hibonite aggregates and spherules, and spinel-pyroxene and elivine-pyroxene inclusions. One of the three spinel-, pyroxene-, forsterite-rich inclusions had an amoeba-shaped spinel-pyroxene core, implying vapor-to-solid condensation and therefore crystallization from a melt. It is concluded that the meteorite formation encompassed diverse nebular materials, and that further studies of the meteorite will enhance the data base on the planetary nebular processes.

Advanced refractory metals and composites for extraterrestrial power systems

NASA Technical Reports Server (NTRS)

Titran, R. H.; Grobstein, Toni L.

1990-01-01

Concepts for future space power systems include nuclear and focused solar heat sources coupled to static and dynamic power-conversion devices; such systems must be designed for service lives as long as 30 years, despite service temperatures of the order of 1600 K. Materials are a critical technology-development factor in such aspects of these systems as reactor fuel containment, environmental protection, power management, and thermal management. Attention is given to the prospective performance of such refractory metals as Nb, W, and Mo alloys, W fiber-reinforced Nb-matrix composites, and HfC precipitate-strengthened W-Re alloys.

Development of wire drawing processes for refractory metal fibers

NASA Technical Reports Server (NTRS)

King, G. W.

1972-01-01

Fabrication schedules were developed for producing wire, 0.25 mm to 0.51 mm diameter, from the refractory metal alloys ASTAR-811C, B-88 and W-Hf-C. Tensile properties were evaluated at room temperature and up to 1204 C. Also, the stress rupture properties of the alloys at 1093 C were determined. W-Hf-C and B-88 were found to have the best mechanical properties on a strength to density basis. The fabrication schedules for producing wire from these two alloys were further improved with regards to the wire quality and material yield under the optimization of fabrication schedule.

Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia.

PubMed

Dretzke, J; Barton, P; Kaambwa, B; Connock, M; Uthman, O; Bayliss, S; Meads, C

2010-10-01

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.

Feasibility of metronomic chemotherapy with tegafur-uracil, cisplatin, and dexamethasone for docetaxel-refractory prostate cancer

PubMed Central

Kubota, Hiroki; Fukuta, Katsuhiro; Yamada, Kenji; Hirose, Masahito; Naruyama, Hiromichi; Yanai, Yoshimasa; Yamada, Yasuyuki; Watase, Hideki; Kawai, Noriyasu; Tozawa, Keiichi; Yasui, Takahiro

2017-01-01

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings. PMID:29255528

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

PubMed

Zschäbitz, Stefanie; Lasitschka, Felix; Hadaschik, Boris; Hofheinz, Ralf-Dieter; Jentsch-Ullrich, Kathleen; Grüner, Marcus; Jäger, Dirk; Grüllich, Carsten

2017-05-01

Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paroxysmal events during prolonged video-video electroencephalography monitoring in refractory epilepsy.

PubMed

Sanabria-Castro, A; Henríquez-Varela, F; Monge-Bonilla, C; Lara-Maier, S; Sittenfeld-Appel, M

2017-03-16

Given that epileptic seizures and non-epileptic paroxysmal events have similar clinical manifestations, using specific diagnostic methods is crucial, especially in patients with drug-resistant epilepsy. Prolonged video electroencephalography monitoring during epileptic seizures reveals epileptiform discharges and has become an essential procedure for epilepsy diagnosis. The main purpose of this study is to characterise paroxysmal events and compare patterns in patients with refractory epilepsy. We conducted a retrospective analysis of medical records from 91 patients diagnosed with refractory epilepsy who underwent prolonged video electroencephalography monitoring during hospitalisation. During prolonged video electroencephalography monitoring, 76.9% of the patients (n=70) had paroxysmal events. The mean number of events was 3.4±2.7; the duration of these events was highly variable. Most patients (80%) experienced seizures during wakefulness. The most common events were focal seizures with altered levels of consciousness, progressive bilateral generalized seizures and psychogenic non-epileptic seizures. Regarding all paroxysmal events, no differences were observed in the number or type of events by sex, in duration by sex or age at onset, or in the number of events by type of event. Psychogenic nonepileptic seizures were predominantly registered during wakefulness, lasted longer, started at older ages, and were more frequent in women. Paroxysmal events recorded during prolonged video electroencephalography monitoring in patients with refractory epilepsy show similar patterns and characteristics to those reported in other latitudes. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

40 CFR 98.460 - Definition of the source category.

Code of Federal Regulations, 2014 CFR

2014-07-01

... foundry sand). (vii) Clay, gypsum, or pottery cull. (viii) Bricks, mortar, or cement. (ix) Furnace slag. (x) Materials used as refractory (e.g., alumina, silicon, fire clay, fire brick). (xi) Plastics (e.g...

40 CFR 98.460 - Definition of the source category.

Code of Federal Regulations, 2012 CFR

2012-07-01

... foundry sand). (vii) Clay, gypsum, or pottery cull. (viii) Bricks, mortar, or cement. (ix) Furnace slag. (x) Materials used as refractory (e.g., alumina, silicon, fire clay, fire brick). (xi) Plastics (e.g...

40 CFR 98.460 - Definition of the source category.

Code of Federal Regulations, 2013 CFR

2013-07-01

... foundry sand). (vii) Clay, gypsum, or pottery cull. (viii) Bricks, mortar, or cement. (ix) Furnace slag. (x) Materials used as refractory (e.g., alumina, silicon, fire clay, fire brick). (xi) Plastics (e.g...

Treatment of advanced refractory sarcomas with ifosfamide and etoposide combination chemotherapy.

PubMed

Yalçin, S; Güllü, I; Barişta, I; Tekuzman, G; Ozişik, Y; Celik, I; Kars, A

1998-01-01

Chemotherapy options for resistant advanced-stage sarcomas are limited and in most cases disappointing. In a phase II study, we treated 26 consecutive patients with refractory advanced sarcoma with ifosfamide and etoposide combination chemotherapy. All patients had received prior doxorubicin- and/or cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were female. The patients' median age was 35 years (range: 19-67 years). A total of 24 patients were eligible for evaluation of responses. Seven patients had a complete response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall 41.6% objective response was achieved. Median time to treatment failure was 13.3 months. A total of 108 cycles of therapy were evaluable for evaluation of toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses, were the most important nonhematological side effects. Alopecia was almost universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded that the combination of ifosfamide, mesna, and etoposide is effective in advanced refractory sarcomas, and has acceptable toxicity.

ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR CHEMOTHERAPY-UNRESPONSIVE MANTLE CELL LYMPHOMA: A COHORT ANALYSIS FROM THE CIBMTR

PubMed Central

Hamadani, Mehdi; Saber, Wael; Ahn, Kwang Woo; Carreras, Jeanette; Cairo, Mitchell S.; Fenske, Timothy S.; Gale, Robert Peter; Gibson, John; Hale, Gregory A.; Hari, Parameswaran N.; Hsu, Jack W.; Inwards, David J.; Kamble, Rammurti T.; Klein, Anderas; Maharaj, Dipnarine; Marks, David I.; Rizzieri, David A.; Savani, Bipin N.; Schouten, Harry C.; Waller, Edmund K.; Wirk, Baldeep; Lazarus, Hillard M.

2013-01-01

Patients with chemorefractory mantle cell lymphoma (MCL) have poor prognosis. We used the CIBMTR database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced intensity/non-myeloablative conditioning (RIC/NST), during 1998–2010. We analyzed non-relapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients received MA, and 128 underwent RIC/NST. Median ages are 54 and 59 years for MA and RIC/NST allo-HCT recipients, respectively. Median follow-up after MA and RIC/NST allo-HCT is 35 months and 43 months, respectively. At 3 years, comparing MA with RIC/NST allo-HCT, no significant differences were found in terms of NRM (47% vs. 43%; p-value=0.68), relapse/progression (33% vs. 32%; p-value=0.89), PFS (20% vs. 25%; p=0.53), and OS (25% vs. 30%; p-value=0.45). On multivariate analysis no significant differences were observed in NRM, relapse, PFS and OS between MA and RIC/NST allo-HCT; however, receiving a bone marrow or T-cell depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Despite a refractory disease state, approximately a fourth of MCL patients can attain durable remissions after allo-HCT. Conditioning regimen intensity did not influence the outcomes of patients after allo HCT. PMID:23333532

Materials technology for coal-conversion processes. Seventeenth quarterly report, January-March 1979

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

Ellingson, W. A.

1979-01-01

Studies of slag attack on refractories were continued, utilizing conditions relevant to MHD applications. Addition of 10 wt % K/sub 2/O seed to the slag did not increase its corrosive effect on the refractories tested. A hot gas-stream cleanup erosion-monitoring system using an ANL-developed nondestructive ultrasonic system was installed at the Morgantown Energy Technology Center (METC) during this period and was 75% completed. Characteristic-slope values obtained from broadband and resonant-band acoustic-emission transducers during rapid heating of a 95% Al/sub 2/O/sub 3/ refractory panel are consistent with theory. Corrosion information on type and thickness of corrosion-product layers was obtained on Incoloymore » 800, 310 stainless steel, Inconel 671 and 871 and 982/sup 0/C. Fluid-bed corrosion studies involving sulfation accelerators have shown that addition of 0.3 mol % CaCl/sub 2/ has no significant effect on corrosion behavior of the alloys studied. However, 0.5 mol % NaCl or 1.9 mol % Na/sub 2/CO/sub 3/ increases the corrosion rates of most materials. Failure analyses were performed on components from the slagging gasifier and liquefaction unit at the Grand Forks Energy Technology Center, and a ball valve from the METC Valve Dynamic Test Unit.« less

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

PubMed Central

Raghunathan, V.; Sethi, S. K.; Dragon-Durey, M. A.; Dhaliwal, M.; Raina, R.; Jha, P.; Bansal, S. B.; Kher, V.

2017-01-01

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency. PMID:28356668

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

PubMed

Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

2018-03-27

Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

The Research Laboratory of Electronics Progress Report Number 133, January 1-December 1990

DTIC Science & Technology

1990-12-31

4 6 Chapter 7 High-Frequency InAlAs/InGaAs Metal -Insulator-Doped Semiconductor...Epitaxy of Compound Semiconductors Chapter 7 High-Frequency InAlAs/InGaAs Metal -Insulator- Doped Semiconductor Field-Effect Transistors (MIDFETs) for...aligned silicided NMOS posed of refractory metals to allow a subsequentdevice fabrication. We have used cobalt deposi- high temperature anneal. This

Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

PubMed Central

Apolo, Andrea B.; Infante, Jeffrey R.; Balmanoukian, Ani; Patel, Manish R.; Wang, Ding; Kelly, Karen; Mega, Anthony E.; Britten, Carolyn D.; Ravaud, Alain; Mita, Alain C.; Safran, Howard; Stinchcombe, Thomas E.; Srdanov, Marko; Gelb, Arnold B.; Schlichting, Michael; Chin, Kevin; Gulley, James L.

2017-01-01

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC. PMID:28375787

Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.

PubMed

Apolo, Andrea B; Infante, Jeffrey R; Balmanoukian, Ani; Patel, Manish R; Wang, Ding; Kelly, Karen; Mega, Anthony E; Britten, Carolyn D; Ravaud, Alain; Mita, Alain C; Safran, Howard; Stinchcombe, Thomas E; Srdanov, Marko; Gelb, Arnold B; Schlichting, Michael; Chin, Kevin; Gulley, James L

2017-07-01

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study.

PubMed

Gopal, Ajay K; Schuster, Stephen J; Fowler, Nathan H; Trotman, Judith; Hess, Georg; Hou, Jing-Zhou; Yacoub, Abdulraheem; Lill, Michael; Martin, Peter; Vitolo, Umberto; Spencer, Andrew; Radford, John; Jurczak, Wojciech; Morton, James; Caballero, Dolores; Deshpande, Sanjay; Gartenberg, Gary J; Wang, Shean-Sheng; Damle, Rajendra N; Schaffer, Michael; Balasubramanian, Sriram; Vermeulen, Jessica; Cheson, Bruce D; Salles, Gilles

2018-05-31

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, ORR was 20.9% (95% CI, 13.7% to 29.7%, which did not meet the 18% lower-bound threshold for the primary end point). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.

Environment Conscious Ceramics (Ecoceramics): An Eco-Friendly Route to Advanced Ceramic Materials

NASA Technical Reports Server (NTRS)

Singh, M.

2001-01-01

Environment conscious ceramics (Ecoceramics) are a new class of materials, which can be produced with renewable natural resources (wood) or wood wastes (wood sawdust). This technology provides an eco-friendly route to advanced ceramic materials. Ecoceramics have tailorable properties and behave like ceramic materials manufactured by conventional approaches. Silicon carbide-based ecoceramics have been fabricated by reactive infiltration of carbonaceous preforms by molten silicon or silicon-refractory metal alloys. The fabrication approach, microstructure, and mechanical properties of SiC-based ecoceramics are presented.

A refractory inclusion returned by Stardust from comet 81P/Wild 2

NASA Astrophysics Data System (ADS)

Simon, S. B.; Joswiak, D. J.; Ishii, H. A.; Bradley, J. P.; Chi, M.; Grossman, L.; AlÉOn, J.; Brownlee, D. E.; Fallon, S.; Hutcheon, I. D.; Matrajt, G.; McKeegan, K. D.

2008-11-01

Among the samples returned from comet 81P/Wild 2 by the Stardust spacecraft is a suite of particles from one impact track (Track 25) that are Ca-, Al-rich and FeO-free. We studied three particles from this track that range in size from 5.3 × 3.2 μ to 15 × 10 μ. Scanning and transmission electron microscopy show that they consist of very fine-grained (typically from ˜0.5 to ˜2 μ) Al-rich, Ti-bearing and Ti-free clinopyroxene, Mg-Al spinel and anorthite, with trace amounts of fine perovskite, FeNi metal and osbornite (TiN) grains. In addition to these phases, the terminal particle, named "Inti", also contains melilite. All of these phases, with the exception of osbornite, are common in refractory inclusions and are predicted to condense at high temperature from a gas of solar composition. Osbornite, though very rare, has also been found in meteoritic refractory inclusions, and could have formed in a region of the nebula where carbon became enriched relative to oxygen compared to solar composition. Compositions of Ti-pyroxene in Inti are similar, but not identical, to those of fassaite from Allende inclusions. Electron energy loss spectroscopy shows that Ti-rich pyroxene in Inti has Ti3+/Ti4+within the range of typical meteoritic fassaite, consistent with formation under reducing conditions comparable to those of a system of solar composition. Inti is 16O-rich, with δ18O?δ17O?-40%0, like unaltered phases in refractory inclusions and refractory IDPs. With grain sizes, mineralogy, mineral chemistry, and an oxygen isotopic composition like those of refractory inclusions, we conclude that Inti is a refractory inclusion that formed in the inner solar nebula. Identification of a particle that formed in the inner solar system among the comet samples demonstrates that there was transport of materials from the inner to the outer nebula, probably either in a bipolar outflow or by turbulence.

Cold machining of high density tungsten and other materials

NASA Technical Reports Server (NTRS)

Ziegelmeier, P.

1969-01-01

Cold machining process, which uses a sub-zero refrigerated cutting fluid, is used for machining refractory or reactive metals and alloys. Special carbide tools for turning and drilling these alloys further improve the cutting performance.

Application of Carbon Composite Bricks for Blast Furnace Hearth

NASA Astrophysics Data System (ADS)

Zuo, Haibin; Wang, Cong; Zhang, Jianliang; Zhao, Yongan; Jiao, Kexin

Traditional refractory materials for blast furnace hearth lining are mainly composed of carbon bricks and the ceramic cup. However, these materials can't meet the demands for long service life design of blast furnaces. In this paper, a new refractory called carbon composite brick (CCB) was introduced, which combined the advantages of carbon bricks and the ceramic cup. In this case, the resistance of the CCB against corrosion was equal to the ceramic cup and the thermal conductivity of the CCB was equal to carbon bricks. From the results of more than 20 blast furnaces, the CCB could be well used in small blast furnaces and large blast furnaces. In the bad condition of low grade burden and high smelting intensity, the CCB gave full play to the role of cooling system, and effectively resisted the erosion of hot metal to improve the service life of blast furnaces.

Stabilized Alumina/Ethanol Colloidal Dispersion for Seeding High Temperature Air Flows

NASA Technical Reports Server (NTRS)

Wernet, Judith H.; Wernet, Mark P.

1994-01-01

Seeding air flows with particles to enable measurements of gas velocities via laser anemometry and/or particle image velocimetry techniques can be quite exasperating. The seeding requirements are compounded when high temperature environments are encountered and special care must be used in selecting a refractory seed material. The pH stabilization techniques commonly employed in ceramic processing are used to obtain stable dispersions for generating aerosols of refractory seed material. By adding submicron alumina particles to a preadjusted pH solution of ethanol, a stable dispersion is obtained which when atomized produces a high quality aerosol. Commercial grade alumina powder is used with a moderate size distribution. The technique is not limited to alumina/ethanol and is also demonstrated with an alumina/H2O system. Other ceramic powders in various polar solvents could also be used once the point of zero charge (pH(sub pzc)) of the powder in the solvent has been determined.

Glenn Refractory Adhesive for Bonding and Exterior Repair (GRABER) Developed for Repairing Shuttle Damage

NASA Technical Reports Server (NTRS)

Singh, Mrityunjay; Shpargel, Tarah P.

2005-01-01

Advanced in-space repair technologies for reinforced carbon/carbon composite (RCC) thermal protection system (TPS) structures are critically needed for the space shuttle Return To Flight (RTF) efforts. These technologies are also critical for the repair and refurbishment of thermal protection system structures of future Crew Exploration Vehicles of space exploration programs. The Glenn Refractory Adhesive for Bonding and Exterior Repair (GRABER) material developed at the NASA Glenn Research Center has demonstrated capabilities for repair of small cracks and damage in RCC leading-edge material. The concept consists of preparing an adhesive paste of desired ceramic in a polymer/phenolic resin matrix with appropriate additives, such as surfactants, and then applying the paste into the damaged or cracked area of the RCC composite components with caulking guns. The adhesive paste cures at 100 to 120 C and transforms into a high-temperature ceramic during simulated vehicle reentry testing conditions.

Uranium carbide fission target R&D for RIA - an update

NASA Astrophysics Data System (ADS)

Greene, J. P.; Levand, A.; Nolen, J.; Burtseva, T.

2004-12-01

For the Rare Isotope Accelerator (RIA) facility, ISOL targets employing refractory compounds of uranium are being developed to produce radioactive ions for post-acceleration. The availability of refractory uranium compounds in forms that have good thermal conductivity, relatively high density, and adequate release properties for short-lived isotopes remains an important issue. Investigations using commercially obtained uranium carbide material and prepared into targets involving various binder materials have been carried out at ANL. Thin sample pellets have been produced for measurements of thermal conductivity using a new method based on electron bombardment with the thermal radiation observed using a two-color optical pyrometer and performed on samples as a function of grain size, pressing pressure and sintering temperature. Manufacture of uranium carbide powder has now been achieved at ANL. Simulations have been carried out on the thermal behavior of the secondary target assembly incorporating various heat shield configurations.

In-situ materials processing systems and bioregenerative life support systems interrelationships

NASA Technical Reports Server (NTRS)

Mignon, George V.; Frye, Robert J.

1992-01-01

The synergy and linkages between bioregenerative life support systems and the materials produced by in-situ materials processing systems was investigated. Such systems produce a broad spectrum of byproducts such as oxygen, hydrogen, processed soil material, ceramics, refractory, and other materials. Some of these materials may be utilized by bioregenerative systems either directly or with minor modifications. The main focus of this project was to investigate how these materials can be utilized to assist a bioregenerative life support system. Clearly the need to provide a sustainable bioregenerative life support system for long term human habitation of space is significant.

Reducing energy consumption and carbon emissions of magnesia refractory products: A life-cycle perspective

DOE PAGES

An, Jing; Li, Yingnan; Middleton, Richard S.

2018-02-20

China is the largest producer of magnesia refractory materials and products in the world, resulting in significant energy consumption and carbon emissions. This paper analyzes measures to reduce both the energy consumption and carbon emissions in the production phase and use phase, providing a theoretical basis for a sustainable magnesia refractory industry. Results show that the total carbon emissions of carbon-containing magnesia bricks produced with fused magnesia are much higher than those of other products, and the total carbon emissions of both general magnesia brick and magnesia-carbon spray are lower than those of other products. Carbon emissions of magnesia productsmore » are mainly concentrated in the production process of magnesia. Manufacturers should select materials with lower environmental impacts and emphasize saving energy and reducing carbon emissions in the magnesia production process. Through scenario analysis we found that CO 2 capture is an effective measure to reduce carbon emissions compared with just improving energy consumption. However, a robust CO 2 market does not currently exist. Policy makers should plan on integrating CO 2 capture in the magnesia industry into a regional CO 2 capture and storage development planning in the long term. In particular, magnesia production is concentrated in a single geographical area which would and thus could take advantage of significant scale effects. Finally, in the use phase, extending the service lifetime reduces carbon emissions over the product lifetime, thus users should attempt to extend the service lifetime of a furnace as a whole. However, results show that it is not advisable to add a large number of repair refractories to extend the lifetime of existing furnaces.« less

Reducing energy consumption and carbon emissions of magnesia refractory products: A life-cycle perspective

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

An, Jing; Li, Yingnan; Middleton, Richard S.

China is the largest producer of magnesia refractory materials and products in the world, resulting in significant energy consumption and carbon emissions. This paper analyzes measures to reduce both the energy consumption and carbon emissions in the production phase and use phase, providing a theoretical basis for a sustainable magnesia refractory industry. Results show that the total carbon emissions of carbon-containing magnesia bricks produced with fused magnesia are much higher than those of other products, and the total carbon emissions of both general magnesia brick and magnesia-carbon spray are lower than those of other products. Carbon emissions of magnesia productsmore » are mainly concentrated in the production process of magnesia. Manufacturers should select materials with lower environmental impacts and emphasize saving energy and reducing carbon emissions in the magnesia production process. Through scenario analysis we found that CO 2 capture is an effective measure to reduce carbon emissions compared with just improving energy consumption. However, a robust CO 2 market does not currently exist. Policy makers should plan on integrating CO 2 capture in the magnesia industry into a regional CO 2 capture and storage development planning in the long term. In particular, magnesia production is concentrated in a single geographical area which would and thus could take advantage of significant scale effects. Finally, in the use phase, extending the service lifetime reduces carbon emissions over the product lifetime, thus users should attempt to extend the service lifetime of a furnace as a whole. However, results show that it is not advisable to add a large number of repair refractories to extend the lifetime of existing furnaces.« less

Dissolution Behavior of Mg from Magnesia-Chromite Refractory into Al-killed Molten Steel

NASA Astrophysics Data System (ADS)

Liu, Chunyang; Yagi, Motoki; Gao, Xu; Kim, Sun-Joong; Huang, Fuxiang; Ueda, Shigeru; Kitamura, Shin-ya

2018-06-01

Magnesia-chromite refractory materials are widely employed in steel production, and are considered a potential MgO source for the generation of MgO·Al2O3 spinel inclusions in steel melts. In this study, a square magnesia-chromite refractory rod was immersed into molten steel of various compositions held in an Al2O3 crucibles. As the immersion time was extended, Mg and Cr gradually dissolved from the magnesia-chromite refractory, and the Mg and Cr contents of the steel melts increased. However, it was found that the inclusions in the steel melts remained as almost pure Al2O3 because the Mg content of the steel melts was low, approximately 1 ppm. On the surface of the magnesia-chromite refractory, an MgO·Al2O3 spinel layer with a variable composition was formed, and the thickness of the MgO·Al2O3 spinel layer increased with the immersion time and the Al content of the steel melts. At the rod interface, the formed layer consisted of MgO-saturated MgO·Al2O3 spinel. The MgO content decreased along the thickness direction of the layer, and at the steel melts interface, the formed layer consisted of Al2O3-saturated MgO·Al2O3 spinel. Therefore, the low content of Mg in steel melts and the unchanged inclusions were because of the equilibrium between Al2O3-saturated MgO·Al2O3 layer and Al2O3. In addition, the effects of the Al and Cr contents of the steel melts on the dissolution of Mg from the magnesia-chromite refractory are insignificant.

Molybdenum disilicide alloy matrix composite

DOEpatents

Petrovic, John J.; Honnell, Richard E.; Gibbs, W. Scott

1991-01-01

Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms.

Fabrication of Smooth Patterned Structures of Refractory Metals, Semiconductors, and Oxides via Template Stripping

PubMed Central

2013-01-01

The template-stripping method can yield smooth patterned films without surface contamination. However, the process is typically limited to coinage metals such as silver and gold because other materials cannot be readily stripped from silicon templates due to strong adhesion. Herein, we report a more general template-stripping method that is applicable to a larger variety of materials, including refractory metals, semiconductors, and oxides. To address the adhesion issue, we introduce a thin gold layer between the template and the deposited materials. After peeling off the combined film from the template, the gold layer can be selectively removed via wet etching to reveal a smooth patterned structure of the desired material. Further, we demonstrate template-stripped multilayer structures that have potential applications for photovoltaics and solar absorbers. An entire patterned device, which can include a transparent conductor, semiconductor absorber, and back contact, can be fabricated. Since our approach can also produce many copies of the patterned structure with high fidelity by reusing the template, a low-cost and high-throughput process in micro- and nanofabrication is provided that is useful for electronics, plasmonics, and nanophotonics. PMID:24001174

Corrosion Studies in Support of Medium Power Lead Alloy Cooled Reactor

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

Eric Loewen; Ronald Ballinger; Jeongyoun Lim

2004-09-01

The performance of structural materials in lead or lead-bismuth eutectic (LBE) systems is evaluated. The materials evaluated included refractory metals (W, Mo, and Ta), several U.S. steels [austenitic steel (316L), carbon steels (F-22, Fe-Si), ferritic/martensitic steels (HT-9 and 410)], and several experimental Fe-Si-Cr alloys that were expected to demonstrate corrosion resistance. The materials were exposed in either an LBE rotating electrode or a dynamic corrosion cell for periods from 100 to 1000 h at temperatures of 400, 500, 600, and 700°C, depending on material and exposure location. Weight change and optical scanning electron microscopy or X-ray analysis of the specimenmore » were used to characterize oxide film thickness, corrosion depth, microstructure, and composition changes. The results of corrosion tests validate the excellent resistance of refractory metals (W, Ta, and Mo) to LBE corrosion. The tests conducted with stainless steels (410, 316L, and HT-9) produced mass transfer of elements (e.g., Ni and Cr) into the LBE, resulting in degradation of the material. With Fe-Si alloys a Si-rich layer (as SiO2) is formed on the surface during exposure to LBE from the selective dissolution of Fe.« less

Corrosion Studies in Support of Medium-Power Lead-Alloy-Cooled Reactor

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

Loewen, Eric P.; Ballinger, Ronald G.; Lim, Jeongyoun

2004-09-15

The performance of structural materials in lead or lead-bismuth eutectic (LBE) systems is evaluated. The materials evaluated included refractory metals (W, Mo, and Ta), several U.S. steels [austenitic steel (316L), carbon steels (F-22, Fe-Si), ferritic/martensitic steels (HT-9 and 410)], and several experimental Fe-Si-Cr alloys that were expected to demonstrate corrosion resistance. The materials were exposed in either an LBE rotating electrode or a dynamic corrosion cell for periods from 100 to 1000 h at temperatures of 400, 500, 600, and 700 deg. C, depending on material and exposure location. Weight change and optical scanning electron microscopy or X-ray analysis ofmore » the specimen were used to characterize oxide film thickness, corrosion depth, microstructure, and composition changes. The results of corrosion tests validate the excellent resistance of refractory metals (W, Ta, and Mo) to LBE corrosion. The tests conducted with stainless steels (410, 316L, and HT-9) produced mass transfer of elements (e.g., Ni and Cr) into the LBE, resulting in degradation of the material. With Fe-Si alloys a Si-rich layer (as SiO{sub 2}) is formed on the surface during exposure to LBE from the selective dissolution of Fe.« less

Fabrication of High Temperature Cermet Materials for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Hickman, Robert; Panda, Binayak; Shah, Sandeep

2005-01-01

Processing techniques are being developed to fabricate refractory metal and ceramic cermet materials for Nuclear Thermal Propulsion (NTP). Significant advances have been made in the area of high-temperature cermet fuel processing since RoverNERVA. Cermet materials offer several advantages such as retention of fission products and fuels, thermal shock resistance, hydrogen compatibility, high conductivity, and high strength. Recent NASA h d e d research has demonstrated the net shape fabrication of W-Re-HfC and other refractory metal and ceramic components that are similar to UN/W-Re cermet fuels. This effort is focused on basic research and characterization to identify the most promising compositions and processing techniques. A particular emphasis is being placed on low cost processes to fabricate near net shape parts of practical size. Several processing methods including Vacuum Plasma Spray (VPS) and conventional PM processes are being evaluated to fabricate material property samples and components. Surrogate W-Re/ZrN cermet fuel materials are being used to develop processing techniques for both coated and uncoated ceramic particles. After process optimization, depleted uranium-based cermets will be fabricated and tested to evaluate mechanical, thermal, and hot H2 erosion properties. This paper provides details on the current results of the project.

Delayed diagnosis of Alport syndrome without hematuria.

PubMed

Yin-Yin, Chen; You-Ming, Peng; Yu-Mei, Liang

2014-05-01

Alport syndrome is a progressive hereditary disease caused by mutations in the genes encoding type IV collagen. Persistent microscopic hematuria is the hallmark of Alport syndrome, occurring in almost all boys according to previous reports. We report the case of a 20-year-old man presented with proteinuria but no hematuria that was initially misdiagnosed with refractory nephrotic syndrome and was eventually diagnosed with Alport syndrome following kidney and skin biopsy. During the follow-up period, he experienced a rapid progression to end-stage renal disease. Timely diagnosis of Alport syndrome is important, because patients may benefit from early intervention and avoid suffering from unnecessary nephrotoxic drug use.

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib.

PubMed

Aguilera, Dolly; Janss, Anna; Mazewski, Claire; Castellino, Robert Craig; Schniederjan, Matthew; Hayes, Laura; Brahma, Barunashish; Fogelgren, Lauren; MacDonald, Tobey J

2016-03-01

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E-positive residual tumor. Vemurafenib (660 mg/m(2) /dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy. © 2015 Wiley Periodicals, Inc.

Condensation of refractory metals in asymptotic giant branch and other stellar environments

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

Schwander, D.; Berg, T.; Schönhense, G.

2014-09-20

The condensation of material from a gas of solar composition has been extensively studied, but less so condensation in the environment of evolved stars, which has been mainly restricted to major compounds and some specific element groups such as the Rare Earth elements. Also of interest, however, are refractory metals like Mo, Ru, Os, W, Ir, and Pt, which may condense to form refractory metal nuggets (RMNs) like the ones that have been found in association with presolar graphite. We have performed calculations describing the condensation of these elements in the outflows of s-process enriched AGB stars as well asmore » from gas enriched in r-process products. While in carbon-rich environments (C > O), the formation of carbides is expected to consume W, Mo, and V (Lodders and Fegley), the condensation sequence for the other refractory metals under these conditions does not significantly differ from the case of a cooling gas of solar composition. The composition in detail, however, is significantly different due to the completely different source composition. Condensation from an r-process enriched source differs less from the solar case. Elemental abundance ratios of the refractory metals can serve as a guide for finding candidate presolar grains among the RMNs in primitive meteorites—most of which have a solar system origin—for confirmation by isotopic analysis. We apply our calculations to the case of the four RMNs found by Croat et al., which may very well be presolar.« less

Light, Strong Insulating Tiles

NASA Technical Reports Server (NTRS)

Cordia, E.; Schirle, J.

1987-01-01

Improved lightweight insulating silica/aluminum borosilicate/silicon carbide tiles combine increased tensile strength with low thermal conductivity. Changes in composition substantially improve heat-insulating properties of silica-based refractory tile. Silicon carbide particles act as high-emissivity radiation scatterers in tile material.

Physical and Chemical Properties of Anthropogenic Aerosols: An Overview

EPA Science Inventory

Aerosol chemical composition is complex. Combustion aerosols can comprise tens of thousands of organic compounds, refractory brown and black carbon, heavy metals, cations, anions, salts, and other inorganic phases. Aerosol organic matter normally contains semivolatile material th...

Interactions between creep, fatigue and strain aging in two refractory alloys

NASA Technical Reports Server (NTRS)

Sheffler, K. D.

1972-01-01

The application of low-amplitude, high-frequency fatigue vibrations during creep testing of two strain-aging refractory alloys (molybdenum-base TZC and tantalum-base T-111) significantly reduced the creep strength of these materials. This strength reduction caused dramatic increases in both the first stage creep strain and the second stage creep rate. The magnitude of the creep rate acceleration varied directly with both frequency and A ratio (ratio of alternating to mean stress), and also varied with temperature, being greatest in the range where the strain-aging phenomenon was most prominent. It was concluded that the creep rate acceleration resulted from a negative strain rate sensitivity which is associated with the strain aging phenomenon in these materials. (A negative rate sensitivity causes flow stress to decrease with increasing strain rate, instead of increasing as in normal materials). By combining two analytical expressions which are normally used to describe creep and strain aging behavior, an expression was developed which correctly described the influence of temperature, frequency, and A ratio on the TZC creep rate acceleration.

Ultra-Heavy Galactic Cosmic Ray Abundances from the SuperTIGER Instrument: evidence for an OB association origin of GCR

NASA Astrophysics Data System (ADS)

Murphy, Ryan; Supertiger Collaboration

2017-01-01

We report Galactic Cosmic Ray (GCR) abundances of elements from 26Fe to 40Zr measured by the SuperTIGER (Trans-Iron Galactic Element Recorder) instrument during 55 days of exposure on a long-duration balloon flight over Antarctica. SuperTIGER measures charge (Z) and energy (E) using a combination of three scintillator and two Cherenkov detectors, and employs a scintillating fiber hodoscope for event trajectory determination. These observations resolve elemental abundances in this charge range with single-element resolution and good statistics. We also derived GCR source abundances, which support a model of cosmic-ray origin in which the source material consists of a mixture of 19-6+ 11 % material from massive stars and 81% normal interstellar medium (ISM) material with solar system abundances. The results also show a preferential acceleration, ordered by atomic mass (A), of refractory elements over volatile elements by a factor of 4. Both the refractory and volatile elements show a mass-dependent enhancement with similar mass dependence. (now AIP Congressional Science Fellow).

Magnetohydrodynamic generator electrode

DOEpatents

Marchant, David D.; Killpatrick, Don H.; Herman, Harold; Kuczen, Kenneth D.

1979-01-01

An improved electrode for use as a current collector in the channel of a magnetohydrodynamid (MHD) generator utilizes an elongated monolithic cap of dense refractory material compliantly mounted to the MHD channel frame for collecting the current. The cap has a central longitudinal channel which contains a first layer of porous refractory ceramic as a high-temperature current leadout from the cap and a second layer of resilient wire mesh in contact with the first layer as a low-temperature current leadout between the first layer and the frame. Also described is a monolithic ceramic insulator compliantly mounted to the frame parallel to the electrode by a plurality of flexible metal strips.

Aluminum reduction cell electrode

DOEpatents

Payne, J.R.

1983-09-20

The invention is directed to an anode-cathode structure for an electrolytic cell for the reduction of alumina wherein the structure is comprised of a carbon anode assembly which straddles a wedge-shaped refractory hard metal cathode assembly having steeply sloped cathodic surfaces, each cathodic surface being paired in essentially parallel planar relationship with an anode surface. The anode-cathode structure not only takes into account the structural weakness of refractory hard metal materials but also permits the changing of the RHM assembly during operation of the cell. Further, the anode-cathode structure enhances the removal of anode gas from the interpolar gap between the anode and cathode surfaces. 10 figs.

Aluminum reduction cell electrode

DOEpatents

Payne, John R.

1983-09-20

The invention is directed to an anode-cathode structure for an electrolytic cell for the reduction of alumina wherein the structure is comprised of a carbon anode assembly which straddles a wedge-shaped refractory hard metal cathode assembly having steeply sloped cathodic surfaces, each cathodic surface being paired in essentially parallel planar relationship with an anode surface. The anode-cathode structure not only takes into account the structural weakness of refractory hard metal materials but also permits the changing of the RHM assembly during operation of the cell. Further, the anode-cathode structure enhances the removal of anode gas from the interpolar gap between the anode and cathode surfaces.

Relation of Salivary PAF Periodontal Disease in Periodontal Maintenance and Refractory Periodontitis Patients

DTIC Science & Technology

1991-05-01

Knox, 1974). Studies have demonstrated the presence of streptococci and lactobacilli throughout the oral cavity , as well as in developing dental... oral cavity , it is apparent that these compounds have the potential to play a role in the initiation and progression of inflammatory oral disease...junctional epithelium and into the gingival sulcus and oral cavity . The perivascular connective tissue matrix becomes altered most likely by

Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin

PubMed Central

Advani, Ranjana H.; Bartlett, Nancy L.; Jacobsen, Eric D.; Sharman, Jeff P.; O’Connor, Owen A.; Siddiqi, Tanya; Kennedy, Dana A.; Oki, Yasuhiro

2014-01-01

This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30+ non-Hodgkin lymphomas. The primary end point was objective response rate (ORR). Key secondary end points included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until progression or unacceptable toxicity. This planned subset analysis included patients with peripheral T-cell lymphomas (PTCLs; n = 35), specifically angioimmunoblastic T-cell lymphoma (AITL; n = 13) and PTCL not otherwise specified (n = 22). Median age was 64 years; 63% were refractory to most recent therapy. Of 34 evaluable patients, ORR was 41% (8 complete remissions [CRs], 6 partial remissions [PRs]), and ORR was 54% in AITL (5 CRs, 2 PRs) with median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were consistent with the known profile of brentuximab vedotin, and included at least grade 3 events of neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL particularly AITL. This trial was registered at www.clinicaltrials.gov as #NCT01421667. PMID:24652992

Recent progress in ankylosing spondylitis treatment.

PubMed

Toussirot, Eric; Wendling, Daniel

2003-01-01

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and loss of functional capacity. The therapeutic management of AS includes regular physical exercise together with the use of NSAIDs. Second-line treatments, such as sulfasalazine, are required in cases of NSAID-refractory AS. Some patients have severe and inadequately controlled disease, explaining the need for the development of new treatments. This therapeutic development in AS involves the assessment of new NSAIDs, namely COX2 selective agents and new second-line treatments, such as methotrexate (MTX), pamidronate and anti-TNFalpha agents. Controlled studies are lacking for MTX. Pamidronate showed to be effective in NSAID refractory AS patients in open and controlled trials. Anti-TNFalpha agents (infliximab and etanercept) gave promising results with dramatic improvement of AS symptoms in open and preliminary controlled trials, but further studies are required to evaluate the real long-term effects and tolerability of these drugs.

Occipital neuralgia secondary to unilateral atlantoaxial osteoarthritis: Case report and review of the literature.

PubMed

Guha, Daipayan; Mohanty, Chandan; Tator, Charles H; Shamji, Mohammed F

2015-01-01

Atlantoaxial osteoarthritis (AAOA), either in isolation or in the context of generalized peripheral or spinal arthritis, presents most commonly with neck pain and limitation of cervical rotational range of motion. Occipital neuralgia (ON) is only rarely attributed to AAOA, as fewer than 30 cases are described in the literature. A 64-year-old female presented with progressive incapacitating cervicalgia and occipital headaches, refractory to medications, and local anesthetic blocks. Computed tomography and magnetic resonance imaging studies documented advanced unilateral atlantoaxial arthrosis with osteophytic compression that dorsally displaced the associated C2 nerve root. Surgical decompression and atlantoaxial fusion achieved rapid and complete relief of neuralgia. Ultimately, postoperative spinal imaging revealed osseous union. Atlantoaxial arthrosis must be considered in the differential diagnosis of ON. Surgical treatment is effective for managing refractory cases. Intraoperative neuronavigation is also a useful adjunct to guide instrumentation and the intraoperative extent of bony decompression.

Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PubMed

Yoshino, Kiyoshi; Kamiura, Shoji; Yokoi, Takeshi; Nakae, Ruriko; Fujita, Masami; Takemura, Masahiko; Adachi, Kazushige; Wakimoto, Akinori; Nishizaki, Takamichi; Shiki, Yasuhiko; Tsutsui, Tateki; Kanda, Yuki; Kobayashi, Eiji; Hashimoto, Kae; Mabuchi, Seiji; Ueda, Yutaka; Sawada, Kenjiro; Tomimatsu, Takuji; Kimura, Tadashi

2017-12-01

To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m 2 , respectively; level 2: 100 and 1000 mg/m 2 ) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m 2 irinotecan and 1000 mg/m 2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Reflections on the Anopheles gambiae genome sequence, transgenic mosquitoes and the prospect for controlling malaria and other vector borne diseases.

PubMed

Tabachnick, Walter J

2003-09-01

The completion of the Anopheles gambiae Giles genome sequencing project is a milestone toward developing more effective strategies in reducing the impact of malaria and other vector borne diseases. The successes in developing transgenic approaches using mosquitoes have provided another essential new tool for further progress in basic vector genetics and the goal of disease control. The use of transgenic approaches to develop refractory mosquitoes is also possible. The ability to use genome sequence to identify genes, and transgenic approaches to construct refractory mosquitoes, has provided the opportunity that with the future development of an appropriate genetic drive system, refractory transgenes can be released into vector populations leading to nontransmitting mosquitoes. An. gambiae populations incapable of transmitting malaria. This compelling strategy will be very difficult to achieve and will require a broad substantial research program for success. The fundamental information that is required on genome structure, gene function and environmental effects on genetic expression are largely unknown. The ability to predict gene effects on phenotype is rudimentary, particularly in natural populations. As a result, the release of a refractory transgene into natural mosquito populations is imprecise and there is little ability to predict unintended consequences. The new genetic tools at hand provide opportunities to address an array of important issues, many of which can have immediate impact on the effectiveness of a host of strategies to control vector borne disease. Transgenic release approaches represent only one strategy that should be pursued. A balanced research program is required.

Filtering coal-derived oil through a filter media precoated with particles partially solubilized by said oil

DOEpatents

Rodgers, Billy R.; Edwards, Michael S.

1977-01-01

Solids such as char, ash, and refractory organic compounds are removed from coal-derived liquids from coal liquefaction processes by the pressure precoat filtration method using particles of 85-350 mesh material selected from the group of bituminous coal, anthracite coal, lignite, and devolatilized coals as precoat materials and as body feed to the unfiltered coal-derived liquid.

Fabrication and surface characterization of composite refractory compounds suitable for thermionic converters

NASA Technical Reports Server (NTRS)

Davis, P. R.; Swanson, L. W.

1979-01-01

The techniques of fabricating and characterizing the surface properties of electrode materials were investigated. The basic surface properties of these materials were studied with respect to their utilization as thermionic energy converter electrodes. Emphasis was placed on those factors (e.g, cesium disorption kinetic and mechanisms of low work function production) which are of primary concern to thermionic converter performance.

Molybdenum disilicide alloy matrix composite

DOEpatents

Petrovic, J.J.; Honnell, R.E.; Gibbs, W.S.

1991-12-03

Compositions of matter consisting of matrix materials having silicon carbide dispersed throughout them and methods of making the compositions are disclosed. A matrix material is an alloy of an intermetallic compound, molybdenum disilicide, and at least one secondary component which is a refractory silicide. The silicon carbide dispersant may be in the form of VLS whiskers, VS whiskers, or submicron powder or a mixture of these forms. 3 figures.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

PubMed

Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Rodríguez-Moranta, F; Márquez, L; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; LLaó, J; Gisbert, J P; Aguas, M; Arias, L; Rodríguez-Lago, I; Muñoz, C; Alcaide, N; Calvet, X; Rodríguez, C; Montoro, M A; García, S; De Castro, M L; Piqueras, M; Pareja, L; Ribes, J; Panés, J; Esteve, M

2018-05-01

Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Apparatus facilitates high-temperature tensile testing in vacuum

NASA Technical Reports Server (NTRS)

Sikora, P. F.

1964-01-01

An apparutus for heating refractory materials to high temperatures during tensile testing includes a water-cooled stainless steel vacuum chamber. This contains a resistance heater consisting of a slit tube of tantalum or tungsten to enclose the tensile test rod.

Coatings for aircraft gas turbine engines and space shuttle heat shields: A review of Lewis Research Center programs

NASA Technical Reports Server (NTRS)

Grisaffe, S. J.; Merutka, J. P.

1972-01-01

The status of several coating programs is reviewed. These include efforts on protecting aircraft gas turbine engine materials from oxidation/corrosion and on protecting refractory metal reentry heat shields from oxidation.

Method of removing sulfur emissions from a fluidized-bed combustion process

DOEpatents

Vogel, Gerhard John; Jonke, Albert A.; Snyder, Robert B.

1978-01-01

Alkali metal or alkaline earth metal oxides are impregnated within refractory support material such as alumina and introduced into a fluidized-bed process for the combustion of coal. Sulfur dioxide produced during combustion reacts with the metal oxide to form metal sulfates within the porous support material. The support material is removed from the process and the metal sulfate regenerated to metal oxide by chemical reduction. Suitable pore sizes are originally developed within the support material by heat-treating to accommodate both the sulfation and regeneration while still maintaining good particle strength.

Nanostructured refractory thin films for solar applications

NASA Astrophysics Data System (ADS)

Ollier, E.; Dunoyer, N.; Dellea, O.; Szambolics, H.

2014-08-01

Selective solar absorbers are key elements of all solar thermal systems. Solar thermal panels and Concentrated Solar Power (CSP) systems aim respectively at producing heat and electricity. In both cases, a surface receives the solar radiation and is designed to have the highest optical absorption (lowest optical reflectivity) of the solar radiation in the visible wavelength range where the solar intensity is the highest. It also has a low emissivity in the infrared (IR) range in order to avoid radiative thermal losses. Current solutions in the state of the art usually consist in deposited interferential thin films or in cermets [1]. Structured surfaces have been proposed and have been simulated because they are supposed to be more efficient when the solar radiation is not normal to the receiving surface and because they could potentially be fabricated with refractory materials able to sustain high operating temperatures. This work presents a new method to fabricate micro/nanostructured surfaces on molybdenum (refractory metal with a melting temperature of 2623°C). This method now allows obtaining a refractory selective surface with an excellent optical selectivity and a very high absorption in the visible range. This high absorption performance was obtained by achieving a double structuration at micro and nano scales thanks to an innovative process flow.

Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer.

PubMed

Nanjo, Shigeki; Hata, Akito; Okuda, Chiyuki; Kaji, Reiko; Okada, Hideaki; Tamura, Daisuke; Irie, Kei; Okada, Hiroshi; Fukushima, Shoji; Katakami, Nobuyuki

2018-01-01

Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose. T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled. We investigated 13 patients (5 definitive and 8 possible LM cases). In two of the five definitive cases with T790M in and outside the central nervous system (CNS), osimertinib was effective for both lesions, with cerebrospinal fluid (CSF) clearance of cancer cells and sensitive/T790M mutations. In three definitive cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive mutations in the CSF persisted after osimertinib initiation. The median progression-free survival of all 13 patients was 7.2 months. Osimertinib was generally well-tolerated despite poor performance status, but interstitial lung disease (grade 2) was confirmed in one patient. Based on 25 samples from 13 patients, the osimertinib CSF penetration rate was 2.5±0.3%. Osimertinib 80 mg is a useful therapeutic option for refractory LM after classical EGFR-TKI failure. It appears more effective in CSF T790M-positive cases.

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

PubMed

Broccoli, Alessandro; Casadei, Beatrice; Morigi, Alice; Sottotetti, Federico; Gotti, Manuel; Spina, Michele; Volpetti, Stefano; Ferrero, Simone; Spina, Francesco; Pisani, Francesco; Merli, Michele; Visco, Carlo; Paolini, Rossella; Zilioli, Vittorio Ruggero; Baldini, Luca; Di Renzo, Nicola; Tosi, Patrizia; Cascavilla, Nicola; Molica, Stefano; Ilariucci, Fiorella; Rigolin, Gian Matteo; D'Alò, Francesco; Vanazzi, Anna; Santambrogio, Elisa; Marasca, Roberto; Mastrullo, Lucia; Castellino, Claudia; Desabbata, Giovanni; Scortechini, Ilaria; Trentin, Livio; Morello, Lucia; Argnani, Lisa; Zinzani, Pier Luigi

2018-05-04

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.

Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

PubMed

Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

1999-02-01

Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

Prolonged myelosuppression with clofarabine in the treatment of patients with relapsed or refractory, aggressive non-Hodgkin lymphoma

PubMed Central

BLUM, KRISTIE A.; HAMADANI, MEHDI; PHILLIPS, GARY S.; LOZANSKI, GERARD; JOHNSON, AMY J.; LUCAS, DAVID M.; SMITH, LISA L.; BAIOCCHI, ROBERT; LIN, THOMAS S.; PORCU, PIERLUIGI; DEVINE, STEVEN M.; BYRD, JOHN C.

2013-01-01

We evaluated the safety and efficacy of the purine nucleoside analogue, clofarabine, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Six patients with DLBCL (n = 5) or MCL (n = 1) and a median age of 68 years were treated with 40 mg/m2 clofarabine IV over 2 h for 5 days, repeated every 28 days, for 1–2 cycles. The overall response rate was 50% (complete response = 1, complete response unconfirmed = 1, partial response = 1). Median progression-free survival was 3.5 months (range 1.5–10 months) and the median overall survival was 7.8 months (range 3–31 months). Grade 3–4 neutropenia and thrombocytopenia was universal, with a median of 34 (range 19–55) and 77 (range 0–275) days required for neutrophil and platelet recovery. Grade 3 non-hematologic toxicities included transaminitis, febrile neutropenia, non-neutropenic infections and orthostatic hypotension. Further accrual to the study was terminated due to prolonged Grade 3–4 myelosuppression and orthostatic hypotension in five of six patients. Clofarabine exhibits evidence of single agent activity in relapsed or refractory DLBCL. However, further study with novel administration schedules that maintain this efficacy and limit toxicity is warranted. PMID:19263294

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Tolvaptan as an alternative treatment for refractory fluid retention associated with sinusoidal obstruction syndrome after allogeneic stem cell transplantation.

PubMed

Yakushijin, Kimikazu; Yamamoto, Katsuya; Kurata, Keiji; Miyata, Yoshiharu; Kakiuchi, Seiji; Tomioka, Hideo; Kawamori-Iwamoto, Yuriko; Inui, Yumiko; Sanada, Yukinari; Okamura, Atsuo; Murayama, Tohru; Matsuoka, Hiroshi; Minami, Hironobu

2013-02-01

Tolvaptan is an oral vasopressin V2-receptor antagonist recognized as effective for fluid retention associated with congestive heart failure and liver cirrhosis. However, there have been no reports concerning clinical experience with tolvaptan for sinusoidal obstruction syndrome (SOS). A 42-year-old male with primarily refractory T-lymphoblastic lymphoma underwent allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor. The myeloablative conditioning regimen consisted of busulfan and cyclophosphamide. On day 20, the total bilirubin level was elevated to 2.0 mg/dL, and body weight increased from 76 to 85 kg, allowing a diagnosis of SOS to be made. Treatments with thrombomodulin, furosemide, carperitide, and low-dose dopamine were ineffective. By day 27, the patient's body weight had increased to 90 kg, and he subsequently developed cardiopulmonary failure. Therefore, we administered low-dose tolvaptan for 2 days (3.75 mg on day 27 and 7.5 mg on day 28). Consequently, his ascites and edema were significantly reduced, and body weight returned to 77 kg by day 34. However, he died of lymphoma progression on day 55. Tolvaptan may be an alternative and promising treatment for refractory fluid retention associated with SOS, although it is unclear whether tolvaptan administration leads to improvement in clinical outcome.

Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

PubMed

Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

2017-08-22

Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres

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

Paprottka, Philipp M., E-mail: philipp.paprottka@med.uni-muenchen.de; Hoffmann, Ralf-T.; Haug, Alexander

2012-04-15

Purpose: To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). Materials and Methods: Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ({sup 90}Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. Results: The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% ofmore » patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. Conclusion: Radioembolization with {sup 90}Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.« less

Transcatheter Arterial Embolization with N-Butyl-2-Cyanoacrylate in the Management of Spontaneous Hematomas

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

Ozyer, Umut, E-mail: umutozyer@gmail.com

IntroductionSpontaneous hematoma refractory to conservative management is a potentially serious condition that requires prompt diagnosis and intervention. The purpose of this study was to evaluate the performance of computed tomography (CT) in the treatment planning and to report the effectiveness of transcatheter embolization with N-butyl-2-cyanoacrylate (NBCA).Materials and MethodsForty-one interventions in 38 patients within a 12-year period were evaluated. CT and angiograms were reviewed for the location of the hematoma, the presence of extravasation, and the correlation of CT and angiography findings.ResultsArterial extravasation was present on 34/39 CT scans. Angiograms confirmed the CT scans in 29 cases. Angiograms revealed extravasation inmore » four cases which CT showed venous bleeding (n = 2) or no bleeding (n = 2). Five patients with arterial and 1 patient with venous extravasation on CT images had no extravasation on angiograms. Embolization was performed to all arteries with extravasation on angiograms. Empiric embolization of the corresponding artery on the CT was performed when there was no extravasation on angiograms. Embolization procedures were performed with 15 % NBCA diluted with iodized oil. Technical success was achieved in 40/41 (97.6 %) interventions. Clinical success was achieved in 35 patients with a single, in 1 patient with 2, and in 1 patient with 3 interventions. No complications related to embolization procedure occurred. None of the patients died due to a progression of the hematoma.ConclusionNBCA is an effective and safe embolic agent to treat hematoma refractory to conservative management. Contrast-enhanced CT may provide faster and more effective intervention.Level of Evidence IIIRetrospective.« less

Elevated temperature strain gages

NASA Technical Reports Server (NTRS)

Brittain, J. O.; Geslin, D.; Lei, J. F.

1986-01-01

One of the goals of the HOST Program is the development of electrical resistance strain gages for static strain measurements at temperatures equal to or greater than 1273 K. Strain gage materials must have a reproducible or predictable response to temperature, time and strain. It is the objective of this research to investigate criteria for the selection of materials for such applications through electrical properties studies. The results of the investigation of two groups of materials, refractory compounds and binary alloy solid solutions are presented.

Combustion synthesis method and products

DOEpatents

Holt, J.B.; Kelly, M.

1993-03-30

Disclosed is a method of producing dense refractory products, comprising: (a) obtaining a quantity of exoergic material in powder form capable of sustaining a combustion synthesis reaction; (b) removing absorbed water vapor therefrom; (c) cold-pressing said material into a formed body; (d) plasma spraying said formed body with a molten exoergic material to form a coat thereon; and (e) igniting said exoergic coated formed body under an inert gas atmosphere and pressure to produce self-sustained combustion synthesis. Also disclosed are products produced by the method.

Combustion synthesis method and products

DOEpatents

Holt, J. Birch; Kelly, Michael

1993-01-01

Disclosed is a method of producing dense refractory products, comprising: (a) obtaining a quantity of exoergic material in powder form capable of sustaining a combustion synthesis reaction; (b) removing absorbed water vapor therefrom; (c) cold-pressing said material into a formed body; (d) plasma spraying said formed body with a molten exoergic material to form a coat thereon; and (e) igniting said exoergic coated formed body under an inert gas atmosphere and pressure to produce self-sustained combustion synthesis. Also disclosed are products produced by the method.

Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group.

PubMed

Kollmannsberger, C; Rick, O; Klaproth, H; Kubin, T; Sayer, H G; Hentrich, M; Welslau, M; Mayer, F; Kuczyk, M; Spott, C; Kanz, L; Bokemeyer, C

2002-09-23

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was administered at a dose of 300 (-350) mg m(-2) every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19-53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4-12) cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose chemotherapy with blood stem cell support. Median number of irinotecan applications was two (1-3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3 degrees anaemia (two patients), common toxicity criteria 3 degrees leukocytopenia (one patient) and common toxicity criteria 3 degrees thrombocytopenia (three patients). Common toxicity criteria 3/4 degrees non-haematological toxicity occurred in five patients (33%): 1 x diarrhoea, 2 x alopecia, 1 x fever and in one patient worsening of pre-existing peripheral polyneuropathy from 1 degrees to 4 degrees. No response was observed to irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting. Irinotecan at a dose of 300-350 mg m(-2) every 3 weeks appears to have no antitumour activity in patients with cisplatin-refractory germ cell cancer and, thus, further investigation in this disease is not justified.

Determinants and predictors of outcome in super refractory status epilepticus--a developing country perspective.

PubMed

Jayalakshmi, Sita; Ruikar, Devashish; Vooturi, Sudhindra; Alladi, Suvarna; Sahu, Sambit; Kaul, Subhash; Mohandas, Surath

2014-11-01

Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p<0.01), elderly (21.7%; p<0.003), and in incident SE (82.1%, p=0.05). Encephalitis was the commonest etiology in RSE (30.9%, p=0.015), SRSE (66.7%, p<0.001) than NRSE (12.3%). Encephalitis (β=8.250 (1.8-37.82); p=0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35.7%), both significantly (p<0.001) higher than NRSE (6.7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p=0.001). Acidosis predicted mortality in the entire cohort (β=7.313 (1.6-32.58); p=0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p=0.055), and NRSE (33.3% vs. 79.1%; p<0.0001). SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with SRSE survived and one third had good outcome. Therefore one should continue the care inspite of weeks of SE. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of Rail Gun Bore Residue

DTIC Science & Technology

1984-03-01

erosion effects and elemental analysis of refractory materials. C. A. L. Westerdahl , J. Pinto, G. L. Ferventino, D. N. Saherhavth...accelerator facility at Large Caliber Weapons Systems Laboratory Dover, New Jersey. ’ 16 REFERENCES 1. C.A.L. Westerdahl , J. Pinto, G. L. Ferrentino, D

USE OF GRANULAR GRAPHITE FOR ELECTROLYTIC DECHLORINATION OF TRICHLOROETHYLENE

EPA Science Inventory

Granular graphite is a potential electrode material for the electrochemical remediation of refractory chlorinated organic compounds such as trichloroethylene (TCE). However, the use of granular graphite can complicate the experimental results. On one hand, up to 99% of TCE was re...

Experimental Design for Evaluation of Co-extruded Refractory Metal/Nickel Base Superalloy Joints

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

ME Petrichek

2005-12-16

Prior to the restructuring of the Prometheus Program, the NRPCT was tasked with delivering a nuclear space reactor. Potential NRPCT nuclear space reactor designs for the Prometheus Project required dissimilar materials to be in contact with each other while operating at extreme temperatures under irradiation. As a result of the high reactor core temperatures, refractory metals were the primary candidates for many of the reactor structural and cladding components. They included the tantalum-base alloys ASTAR-811C and Ta-10W, the niobium-base alloy FS-85, and the molybdenum base alloys Moly 41-47.5 Rhenium. The refractory metals were to be joined to candidate nickel basemore » alloys such as Haynes 230, Alloy 617, or Nimonic PE 16 either within the core if the nickel-base alloys were ultimately selected to form the outer core barrel, or at a location exterior to the core if the nickel-base alloys were limited to components exterior to the core. To support the need for dissimilar metal joints in the Prometheus Project, a co-extrusion experiment was proposed. There are several potential methods for the formation of dissimilar metal joints, including explosive bonding, friction stir welding, plasma spray, inertia welding, HIP, and co-extrusion. Most of these joining methods are not viable options because they result in the immediate formation of brittle intermetallics. Upon cooling, intermetallics form in the weld fusion zone between the joined metals. Because brittle intermetallics do not form during the initial bonding process associated with HIP, co-extrusion, and explosive bonding, these three joining procedures are preferred for forming dissimilar metal joints. In reference to a Westinghouse Astronuclear Laboratory report done under a NASA sponsored program, joints that were fabricated between similar materials via explosive bonding had strengths that were directly affected by the width of the diffusion barrier. It was determined that the diffusion zone should not exceed a critical thickness (0.0005 in.). A diffusion barrier that exceeded this thickness would likely fail. The joint fabrication method must therefore mechanically bond the two materials causing little or no interdiffusion upon formation. Co-extrusion fits this description since it forms a mechanical joint between two materials by using heat and pressure. The two materials to be extruded are first assembled and sealed within a co-extrusion billet which is subsequently heated and then extruded through a die. For a production application, once the joint is formed, it is dejacketed to remove the outer canister. The remaining piece consists of two materials bonded together with a thin diffusion barrier. Therefore, the long-term stability of the joint is determined primarily by the kinetics of interdiffusion reaction between the two materials. An experimental design for co-extrusion of refractory metals and nickel-based superalloys was developed to evaluate this joining process and determine the long-term stability of the joints.« less

Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma

PubMed Central

Mehrzad, Valiollah; Ashrafi, Farzaneh; Farrashi, Ali Reza; Pourmarjani, Reyhaneh; Dehghani, Mehdi; Shahsanaei, Armindokht

2017-01-01

Background: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of patients. The treatment of choice for these patients is high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to salvage chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT. However, its applicability is restricted mostly to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin, and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of relapsed or refractory HD. Materials and Methods: In this retrospective analysis, 114 patients with primary refractory or relapsed HD who received ICE or ESHAP salvage regimen were included. Results: Of 114 patients, 47 (41.2%) were females and the median age was 31.5 years. Response could be evaluated in 114 patients. Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%) achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the evaluable ICE group (n = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39% and in the ESHAP group (n = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and 58.9% (for ORR, P = 0.04), respectively. Conclusion: In patients with relapsed or refractory HD, treatment with ESHAP seems to have higher rates of response than ICE regimen does. PMID:28401077

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost

PubMed Central

Kurdoğlu, Zehra; Carr, Danielle; Harmouche, Jihad; Ünlü, Serdar; Kılıç, Gökhan S.

2018-01-01

Objective: Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. Material and Methods: We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. Results: Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. Conclusion: PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits. PMID:29503256

Wire EDM for Refractory Materials

NASA Technical Reports Server (NTRS)

Zellars, G. R.; Harris, F. E.; Lowell, C. E.; Pollman, W. M.; Rys, V. J.; Wills, R. J.

1982-01-01

In an attempt to reduce fabrication time and costs, Wire Electrical Discharge Machine (Wire EDM) method was investigated as tool for fabricating matched blade roots and disk slots. Eight high-strength nickel-base superalloys were used. Computer-controlled Wire EDM technique provided high quality surfaces with excellent dimensional tolerances. Wire EDM method offers potential for substantial reductions in fabrication costs for "hard to machine" alloys and electrically conductive materials in specific high-precision applications.

The development of Nb-based advanced intermetallic alloys for structural applications

NASA Astrophysics Data System (ADS)

Subramanian, P. R.; Mendiratta, M. G.; Dimiduk, D. M.

1996-01-01

A new generation of refractory material systems with significant increases in temperature capability is required to meet the demands of future aerospace applications. Such materials require a balance of properties such as low-temperature damage tolerance, high-temperature strength, creep resistance, and superior environmental stability for implementation in advanced aerospace systems. Systems incorporating niobium-based beta alloys and intermetallic compounds have the potential for meeting these requirements.

Investigation into Suitability of Geopolymers (Illite & Metakaolin) for the Space Environment

DTIC Science & Technology

2012-09-13

most disastrous if a spacecraft telescope made of a hybrid composite mirror with a geopolymer adhesive became distorted or damaged on orbit due to...background According to the Dictionary of Composite Materials Technology, (Lee 1989) a geopolymer is defined as: “A family of refractory ceramics...polysilicates to form polymeric Si-O-Al bonds”. Geopolymers and geopolymer composites are a relatively newly defined class of ceramic materials whose

Method for Forming Fiber Reinforced Composite Bodies with Graded Composition and Stress Zones

NASA Technical Reports Server (NTRS)

Singh, Mrityunjay (Inventor); Levine, Stanley R. (Inventor); Smialek, James A. (Inventor)

1999-01-01

A near-net, complex shaped ceramic fiber reinforced silicon carbide based composite bodies with graded compositions and stress zones is disclosed. To provide the composite a fiber preform is first fabricated and an interphase is applied by chemical vapor infiltration, sol-gel or polymer processes. This first body is further infiltrated with a polymer mixture containing carbon, and/or silicon carbide, and additional oxide, carbide, or nitride phases forming a second body. One side of the second body is spray coated or infiltrated with slurries containing high thermal expansion and oxidation resistant. crack sealant phases and the other side of this second body is coated with low expansion phase materials to form a third body. This third body consisting of porous carbonaceous matrix surrounding the previously applied interphase materials, is then infiltrated with molten silicon or molten silicon-refractory metal alloys to form a fourth body. The resulting fourth body comprises dense composites consisting of fibers with the desired interphase which are surrounded by silicon carbide and other second phases materials at the outer and inner surfaces comprising material of silicon, germanium, refractory metal suicides, borides, carbides, oxides, and combinations thereof The resulting composite fourth body has different compositional patterns from one side to the other.

A Refractory Inclusion Returned by Stardust from Comet 81P/Wild 2

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

Simon, S B; Joswiak, D J; Ishii, H A

2008-05-20

Among the samples returned from comet 81P/Wild 2 by the Stardust spacecraft is a suite of particles from one impact track (Track 25) that are Ca-, Al-rich and FeO-free. We studied three particles from this track that range in size from 5.3 x 3.2 {micro}m to 15 x 10 {micro}m. Scanning and transmission electron microscopy show that they consist of very fine-grained (from {approx}0.5 to {approx}2 {micro}m) Al-rich, Ti-bearing and Ti-free clinopyroxene, Mg-Al spinel, anorthite, perovskite, and osbornite (TiN). In addition to these phases, the terminal particle, named 'Inti', also contains melilite. All of these phases, with the exception ofmore » osbornite, are common in refractory inclusions and are predicted to condense at high temperature from a gas of solar composition. Osbornite, though very rare, has also been found in meteoritic refractory inclusions, and could have formed in a region of the nebula where carbon became enriched relative to oxygen compared to solar composition. Compositions of Ti-pyroxene in Inti are similar, but not identical, to those of fassaite from Allende inclusions. Electron energy loss spectroscopy shows that Ti-rich pyroxene in Inti has Ti{sup 3+}/Ti{sup 4+} within the range of typical meteoritic fassaite, consistent with formation under reducing conditions comparable to those of a system of solar composition. Inti is {sup 16}O-rich, with {delta}{sup 18}O {approx} {delta}{sup 17}O {approx} 40{per_thousand}, like unaltered phases in refractory inclusions and refractory IDPs. With grain sizes, mineralogy, mineral chemistry, and an oxygen isotopic composition like those of refractory inclusions, we conclude that Inti is a refractory inclusion that formed in the inner solar nebula. Identification of a particle that formed in the inner Solar System among the comet samples demonstrates that there was transport of materials from the inner to the outer nebula, probably either in a bipolar outflow or by turbulence.« less

Electro Processing Research

NASA Technical Reports Server (NTRS)

1982-01-01

Electroprocessing which is concerned with fluid dynamics of the electroreduction process to determine how it may be modified to improve the quality of the deposit was studied. Experimental techniques are used in this research. These techniques include laser Schlieren photography, laser Doppler velocimetry, and frequency spectrum analysis. Projects involve fluid flow studies of zinc plating in aqueous and molten salt electrolytes, study of cell design for magnesium chlorides electrolysis, digital signal analysis of manganese electrodeposition in molten chlorides, and electroplating of molybdenum from low melting salts. It is anticipated that the use of refractory metals as constructed materials in engineering will increase. Their electrodeposition from molten salt electrolytes is important in the extraction metallurgy of refractory metals.

CRUCIBLE LINING METHOD

DOEpatents

Bone, W.H.; Schmidt, W.W.

1958-11-01

A method is presented for forming refractory liners in cylindrical reaction vessels used for the reductlon of uranium tetrafluoride to metallic uranium. A preliminary form, having positioning lugs attached thereto, is inserted into the reaction vessel and the refractory powder, usually CaO, is put in the annular space between the form and the inner wall of the reaction vessel. A jolting table is used to compact this charge of liner material ln place, and after thls has been done, the preliminary form is removed and the flnal form or plug is lnserted without disturbing the partially completed lining. The remainder of the lining charge is then introduced and compacted by jolting, after which the form is removed.

Magnetohydrodynamic electrode

DOEpatents

Marchant, David D.; Killpatrick, Don H.

1978-01-01

An electrode capable of withstanding high temperatures and suitable for use as a current collector in the channel of a magnetohydrodynamic (MHD) generator consists of a sintered powdered metal base portion, the upper surface of the base being coated with a first layer of nickel aluminide, an intermediate layer of a mixture of nickel aluminide - refractory ceramic on the first layer and a third or outer layer of a refractory ceramic material on the intermediate layer. The sintered powdered metal base resists spalling by the ceramic coatings and permits greater electrode compliance to thermal shock. The density of the powdered metal base can be varied to allow optimization of the thermal conductivity of the electrode and prevent excess heat loss from the channel.

High-temperature Mechanical Properties and Microstructure of ZrTiHfNbMox (x=0.5, 1.0, 1.5) Refractory High Entropy Alloys

NASA Astrophysics Data System (ADS)

Chen, Y. W.; Li, Y. K.; Cheng, X. W.; Wu, C.; Cheng, B.

2018-05-01

Refractory high entropy alloys (RHEAs), with excellent properties at high temperature, have several applications. In this work, the ZrTiHfNbMox (x=0.5, 1.0, 1.5) alloys were prepared by arc melting. All these alloys form body centered cubic (BCC) structure without other intermediate phases. The Mo element contributes to the strength of alloys at high temperature, but too much of Mo decreases the plasticity severely and enhances the strength. The ZrTiHfNbMo alloy, whose compressive stress is 1099 MPa at 800° C, is a promising material for high-temperature applications.

Coal gasification vessel

DOEpatents

Loo, Billy W.

1982-01-01

A vessel system (10) comprises an outer shell (14) of carbon fibers held in a binder, a coolant circulation mechanism (16) and control mechanism (42) and an inner shell (46) comprised of a refractory material and is of light weight and capable of withstanding the extreme temperature and pressure environment of, for example, a coal gasification process. The control mechanism (42) can be computer controlled and can be used to monitor and modulate the coolant which is provided through the circulation mechanism (16) for cooling and protecting the carbon fiber and outer shell (14). The control mechanism (42) is also used to locate any isolated hot spots which may occur through the local disintegration of the inner refractory shell (46).

Valve for abrasive material

DOEpatents

Gardner, Harold S.

1982-01-01

A ball valve assembly for controlling the flow of abrasive particulates including an enlarged section at the bore inlet and an enlarged section at the bore outlet. A refractory ceramic annular deflector is positioned in each of the enlarged sections, substantially extending the useful life of the valve.

Composites of low-density trialuminides: Particulate and long fiber reinforcements

NASA Technical Reports Server (NTRS)

Kumar, K. S.; Dipietro, M. S.; Brown, S. A.; Whittenberger, J. D.

1992-01-01

An examination of the ternary L1(sub 2) trialuminides, Al66Ti25Mn9, Al67Ti25Cr8, and Al22Ti8Fe3 in compression, bending, and tension revealed that none of these compounds exhibited a desirable balance of strength, ductility, and oxidation resistance. Subsequently, specific quaternary and quinary compositions were cast, homogenized, and isothermally forged. Both, the monolithic material and its particulate reinforced counterparts were examined in compression, three point bend, and tension as a function of temperature, and at high temperatures as a function of strain rate. An alternate approach that was examined in this program to enhance the low temperature damage tolerance of these materials was to incorporate long refractory metal wires in the matrix. In summary, it appears that of the various matrix compositions examined, ternary Al66Ti25Mn9 exhibits the best balance in strength, ductility, and oxidation resistance. Although the idea of refractory metal wire reinforcement is an attractive one, a successful combination remains to be identified.

Producibility of fibrous refractory composite insulation, FRCI 40-20. [for reusable heat shielding

NASA Technical Reports Server (NTRS)

Strauss, E. L.; Johnson, C. W.; Graese, R. W.; Campbell, R. L.

1983-01-01

Fibrous Refractory Composite Insulation (FRCI) is a NASA-developed, second generation, reusable heat-shield material that comprises a mixture of aluminoborosilicate fibers, silica fibers, and silicon carbide. Under NASA contract, a program was conducted to demonstrate the capability for manufacturing FRCI 40-20 billets. A detailed fabrication procedure was written and validated by testing specimens from the first two billets. The material conformed to NASA requirements for density, tensile strength, modulus of rupture, thermal expansion, cristobalite content, and uniformity. Twenty-four billets were prepared to provide 20 deliverable articles. Production billets were checked for density, modulus of rupture, cristobalite content, and uniformity. Billet density ranged from 309.48 to 332.22 kg/cu m (19.32 to 20.74 lb/cu ft) and modulus of rupture from 4690 to 10,140 kPa (680 to 1470 psi). Cristobalite content was less than 1 percent. A Weibull analysis of modulus-of-rupture data indicated a 1.5 percent probability for failure below the specified strength of 4480 kPa (650 psi).

Composition, structure and chemistry of interstellar dust

NASA Technical Reports Server (NTRS)

Tielens, Alexander G. G. M.; Allamandola, Louis J.

1986-01-01

The observational constraints on the composition of the interstellar dust are analyzed. The dust in the diffuse interstellar medium consists of a mixture of stardust (amorphous silicates, amorphous carbon, polycyclic aromatic hydrocarbons, and graphite) and interstellar medium dust (organic refractory material). Stardust seems to dominate in the local diffuse interstellar medium. Inside molecular clouds, however, icy grain mantles are also important. The structural differences between crystalline and amorphous materials, which lead to differences in the optical properties, are discussed. The astrophysical consequences are briefly examined. The physical principles of grain surface chemistry are discussed and applied to the formation of molecular hydrogen and icy grain mantles inside dense molecular clouds. Transformation of these icy grain mantles into the organic refractory dust component observed in the diffuse interstellar medium requires ultraviolet sources inside molecular clouds as well as radical diffusion promoted by transient heating of the mantle. The latter process also returns a considerable fraction of the molecules in the grain mantle to the gas phase.

Shaft kilns for firing of refractory raw material on a model of operation of a firing system

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

Utenkov, A.F.; Strekalova, L.V.

1986-09-01

This paper attempts to develop a design of gas burner for providing uniform high-temperature firing of refractory material in shaft kilns. On the model the influence of the following factors on the processes of mass exchange and the character of the gasdynamics was studied: the ratio of the diamters of the gas and air orifices of tube-in-tube type burners and their absolute values with a constant gas consumption; the depth of the gas orifice in relation to the tip of the burner; the form of the initial profile of the velocity of the gasair jet at the outlet from themore » burner; the angle of slope of the burners to the shaft housing; the ratio of the consumption of gas supplied under the shaft and to the gas burners; and the static pressure in the working space at the level of the gas burners.« less

A phase 1/2 dose-finding, safety, and activity study of cabazitaxel in pediatric patients with refractory solid tumors including tumors of the central nervous system.

PubMed

Manley, Peter E; Trippett, Tanya; Smith, Amy A; Macy, Margaret E; Leary, Sarah E S; Boklan, Jessica; Cohen, Kenneth J; Goldman, Stewart; Kilburn, Lindsay B; Dhall, Girish; Devin, Jeanne; Herzog, Cynthia E; Partap, Sonia; Fauchet, Floris; Badreddine, Emmy; Bernard, John P; Chi, Susan N

2018-05-11

This phase 1/2 study (NCT01751308) evaluated cabazitaxel in pediatric patients. Phase 1 determined the maximum tolerated dose (MTD) in patients with recurrent/refractory solid tumors, including central nervous system (CNS) tumors. Phase 2 evaluated activity in pediatric recurrent high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). In phase 1, a 3 + 3 dose-escalation study design was followed. Cabazitaxel was administered at a starting dose of 20 mg/m 2 . Dose-limiting toxicities (DLTs) during cycle 1 were assessed to determine the MTD. Tumor response and cabazitaxel pharmacokinetics were also assessed. In phase 2, patients received cabazitaxel at the MTD determined in phase 1. Tumor responses were assessed every 9 weeks (modified Response Assessment in Neuro-oncology criteria). Progression-free survival and cabazitaxel pharmacokinetics were evaluated, and overall survival was estimated. In phase 1, 23 patients were treated, including 19 with CNS tumors. One patient had a partial response; five had stable disease for >3 cycles. Common adverse events included fatigue, diarrhea, nausea and vomiting, febrile neutropenia, and hypersensitivity reactions. Two of three DLTs (febrile neutropenia) occurred with a dose of 35 mg/m 2 ; the MTD was 30 mg/m 2 . Slightly higher cabazitaxel clearance was observed compared with adult trials. In phase 2, 16 patients (eight HGG and eight DIPG) were enrolled; 11 were evaluable for response and five withdrew (three due to anaphylaxis). All 11 patients progressed within four cycles. No responses were observed; the study was stopped due to futility. The safety profile of cabazitaxel was consistent with previous studies. The MTD (30 mg/m 2 ) was higher than the adult MTD. Cabazitaxel did not demonstrate activity in recurrent/refractory HGG or DIPG. © 2018 Wiley Periodicals, Inc.

Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

PubMed

Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

2014-01-01

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC. © 2014 International Society for Diseases of the Esophagus.

Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?

PubMed

Arora, Sukeshi Patel; Ketchum, Norma S; Michalek, Joel; Gelfond, Jonathon; Mahalingam, Devalingam

2017-04-22

Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test. One hundred thirty-nine patients with a median age 59 (33-81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03). In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.

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

Schuett, K.J.; Pawlak, J.P.; Traina, L.

No. 13 Blast Furnace at US Steel`s Gary Works is a 35 tuyere furnace with a 36.5 ft. hearth capable of producing over 9,000 tons of hot metal per day. The current casthouse design was placed in service following the second reline in the fall of 1979. This design anticipated daily production rates averaging 7,500 tons of hot metal per day and provided for removable troughs at two of the three tapholes. At the time, the troughs were rammed with a high alumina/silicon carbide granular ramming material that provided the operators with trough campaign lives between 60,000--70,000 tons of hotmore » metal produced. As refractory technology progressed, low cement/low moisture castables were introduced to the trough systems on No. 13 Blast Furnace. The immediate success of the castables was tempered by emergence of a new unexpected problem. That problem was the thermal expansion of the castable. The paper describes the problems that resulted in the need to modify the trough design, the new design of the trough, and its improvement in iron trough campaign life and reliability.« less

Composition and Biolability of Dissolved Organic Matter Leached from the Dominant Endmembers of the Siberian Arctic

NASA Astrophysics Data System (ADS)

Borgen, M.; Spencer, R. G.; Mann, P. J.; Vonk, J. E.; Bulygina, E. B.; Holmes, R. M.

2012-12-01

Terrigenous dissolved organic matter (DOM) has historically been thought to be refractory as it is mobilized into and transported through Arctic fluvial networks. However, a growing body of evidence suggests that this DOM, largely leached from vegetation, soils, and litter during the annual freshet, is highly biolabile. This study examined DOM leached from these dominant endmembers of the Kolyma River watershed in the Siberian Arctic. As leachates progressed through time, measurements of dissolved organic carbon (DOC), optical parameters to assess DOM composition, and biodegradation incubations were undertaken. This suite of measurements allowed examination of the rate and composition of leached DOC into the aquatic system and quantification of the biolability of the DOM from the diverse range of endmembers examined. Of all the endmembers, vascular plants leached the greatest amount of DOC and results will be presented relating DOC concentration and DOM composition to initial source material. Furthermore, controls on DOM biolability, enzymatic activity, and the ultimate fate of terriginous DOC in Siberian fluvial systems will be discussed.

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

PubMed Central

Zola, Marta; Briamonte, Cristina; Lorenzi, Umberto; Machetta, Federica; Grignolo, Federico M; Fea, Antonio M

2017-01-01

Purpose The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema. Methods Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT) was 446.3±129.9 μm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically. Conclusion Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. PMID:29184384

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM. PMID:20694078

The Ahmed Glaucoma Valve in Refractory Glaucoma: Experiences in Southwest Ethiopia.

PubMed

Gessesse, Girum W

2015-07-01

The management of refractory glaucoma is a challenging task for any glaucoma surgeon. This study is aimed to evaluate the efficacy of Ahmed Glaucoma Valve implantation in refractory glaucomas in South-West Ethiopia. A retrospective review was conducted on the charts of consecutive patients treated with Ahmed glaucoma valve implantation at Jimma University Specialized Hospital between August 2012 and August 2014. Success was defined as Intraocular Pressure (IOP) less than 22 mm Hg and greater than 5mm Hg at 6 months, with at least 30% reduction from baseline, without medical therapy (complete success) or either with or without medication (qualified successes). A total of 12 eyes of 11 patients were included. The mean age of patients was 40.7 (SD= 19.0) years; 63.6% of them were males. The main types of glaucoma were pseudoexfoliative (3 eyes), uveitic (2 eyes), chronic angle closure (2 eyes) and Juvenile Open Angle (JOAG) (2 eyes). The mean IOP was reduced from preoperative level (32.75±7.14 mmHg) to (15.75 ±4.35 mmHg) at six postoperative months, (P<0.001); 66.7% eyes had complete successes while 83.3% had qualified success. Intra-operative complications were encountered in 2(16.7%) eyes, while 5/12 (41.7%) eyes had post-operative complications-hypotony (one with choroidal effusion) and progression of cataract in 2 eyes each. Hypertensive phase was diagnosed in 2(16.7%) eyes. The Ahmed glaucoma valve implant appears to be effective and relatively safe for treating complicated glaucomas with success rate comparable with those reported from other studies. Ahmed glaucoma valve, refractory glaucoma, complications, Ethiopia.

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.

PubMed

Siegel, David S; Dimopoulos, Meletios; Jagannath, Sundar; Goldschmidt, Hartmut; Durrant, Simon; Kaufman, Jonathan L; Leleu, Xavier; Nagler, Arnon; Offner, Fritz; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Gause, Christine; Vuocolo, Scott; Anderson, Kenneth C

2016-06-01

The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). Copyright © 2016 Elsevier Inc. All rights reserved.

Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma

PubMed Central

Richardson, Paul G.; Weller, Edie; Jagannath, Sundar; Avigan, David E.; Alsina, Melissa; Schlossman, Robert L.; Mazumder, Amitabha; Munshi, Nikhil C.; Ghobrial, Irene M.; Doss, Deborah; Warren, Diane L.; Lunde, Laura E.; McKenney, Mary; Delaney, Carol; Mitsiades, Constantine S.; Hideshima, Teru; Dalton, William; Knight, Robert; Esseltine, Dixie-Lee; Anderson, Kenneth C.

2009-01-01

Purpose Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM. Patients and Methods Patients received lenalidomide 5, 10, or 15 mg/d on days 1 through 14 and received bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20mg or 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) was added for progressive disease after two cycles. Primary end points were safety and MTD determination. Results Thirty-eight patients were enrolled across six dose cohorts. The MTD was lenalidomide 15 mg/d plus bortezomib 1.0 mg/m2. Dose-limiting toxicities (n = 1 for each) were grade 3 hyponatremia and herpes zoster reactivation and grade 4 neutropenia. The most common treatment-related, grades 3 to 4 toxicities included reversible neutropenia, thrombocytopenia, anemia, and leukopenia. Among 36 response-evaluable patients, 61% (90% CI, 46% to 75%) achieved minimal response or better. Among 18 patients who had dexamethasone added, 83% (90% CI, 62% to 95%) achieved stable disease or better. Median overall survival was 37 months. Conclusion Lenalidomide plus bortezomib was well tolerated and showed promising activity with durable responses in patients with relapsed and relapsed/refractory MM, including patients previously treated with lenalidomide, bortezomib, and/or thalidomide. The combination of lenalidomide, bortezomib, and dexamethasone is being investigated in a phase II study in this setting and in newly diagnosed MM. PMID:19786667

The effectiveness and safety of lacosamide in children with epilepsy in a clinical practice setting.

PubMed

Sanmartí-Vilaplana, Francesc; Díaz-Gómez, Asunción

2018-02-01

Seizures in up to 30% of children with epilepsy become refractory to treatment, decreasing their quality of life. Studies suggest that lacosamide may be effective in pediatric patients with refractory epilepsy. To assess the effectiveness and safety of lacosamide in a population of children with mostly focal refractory epilepsy. Retrospective analysis of children aged <18years presenting to a single hospital in Spain. Data from baseline, and 3, 6, and 12months after lacosamide initiation were collected and analyzed. Response to lacosamide was categorized by seizure frequency (seizure freedom or ≥75%, ≥50%, and <50% reduction in seizures). One hundred ninety-one pediatric patients (~55% male) with focal epilepsy treated with lacosamide were included. The mean age at lacosamide initiation was 9.4years, and the mean duration of epilepsy was 5.4years. Seizure-free rates at 3, 6, and 12months were 9.7%, 11.8%, and 16.0%. At 12months, 44.4% of the population had a ≥50% reduction in seizure frequency. When analyzing response according to the number of previous/concomitant AEDs, those patients who received ≤2 previous AEDs/fewer concomitant AEDs had significantly greater response rates than those who received greater numbers of previous/concomitant AEDs; however, no predictive factors for response were identified. The most common adverse events were seizure number increased (14.7%), diplopia (5.2%), dizziness (3.7%), ataxia (2.1%), and drowsiness (2.1%). Lacosamide use in children with refractory focal epilepsy can result in a reduction in seizure rate that improves progressively over time with few adverse effects, making lacosamide a promising option in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma.

PubMed

Li, Ling; Xiao, Sa; Zhang, Lei; Li, Xin; Fu, Xiaorui; Wang, Xinhua; Wu, Jingjing; Sun, Zhenchang; Zhang, Xudong; Chang, Yu; Nan, Feifei; Yan, Jiaqin; Li, Zhaoming; Shi, Mengyuan; Young, Ken H; Zhang, Mingzhi

2018-03-23

Apatinib, a novel small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, have shown remarkable efficacy in many solid cancers. But evidence of antitumor activity in patients with lymphoma is still limited. We conducted an open-label, single-armed, exploratory study in relapse or refractory non-Hodgkin lymphoma patients for the efficacy and safety of apatinib. Patients with relapse or refractory non-Hodgkin patients meet the criteria were eligible for enrollment. Treatment comprised of oral apatinib 500 mg once daily with 21 days as a treatment cycle. The primary end point was response rate. Secondary end points included progression-free survival (PFS) and overall survival (OS). Between February 2016 and December 2016, 21 patients were enrolled. The ORR (CR plus PR) was 47.6% (10 of 21 patients) included 9.5% CRs and 38.1% PRs. 23.8% patients achieved stable disease made the DCR 71.4% (15/21). The median OS was 7.3 months (95% CI, 7.1 to 7.9) and the median PFS was 7.1 months (95% CI, 4.2 to 7.3). Most patients suffered from grade 1 to grade 2 treatment-related adverse events and the most common nonhematologic adverse events were proteinuria (47.6%), hypertension (42.9%) and hand-foot syndrome (33.3%), respectively. In our study, the results we presented showed apatinib might have a rapid, safe and high efficacy on relapsed or refractory non-Hodgkin lymphoma patients. Based on the data more clinic trials are expected to be taken to identification the efficacy of apatinib on lymphoma further.

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

PubMed Central

Suvannasankha, Attaya; Fay, Joseph W.; Arnulf, Bertrand; Kaufman, Jonathan L.; Ifthikharuddin, Jainulabdeen J.; Weiss, Brendan M.; Krishnan, Amrita; Lentzsch, Suzanne; Comenzo, Raymond; Wang, Jianping; Nottage, Kerri; Chiu, Christopher; Khokhar, Nushmia Z.; Ahmadi, Tahamtan; Lonial, Sagar

2017-01-01

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received ≥3 prior therapies. The safety profile of daratumumab plus pom-dex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ≥3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10−5. Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971. PMID:28637662

Eligibility of real-world patients with chemo-refractory, K-RAS wild-type, metastatic colorectal cancer for palliative intent regorafenib monotherapy.

PubMed

Angeles, Arkhjamil; Hung, Wayne; Cheung, Winson Y

2018-06-23

The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.

131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma.

PubMed

French, Sarah; DuBois, Steven G; Horn, Biljana; Granger, Meaghan; Hawkins, Randall; Pass, Amy; Plummer, Ellen; Matthay, Katherine

2013-05-01

(131) I-metaiodobenzylguanidine (MIBG) produces a 37% response rate in relapsed/refractory neuroblastoma, and could be used to improve remission status prior to myeloablative chemotherapy with autologous stem cell transplant (ASCT). The purpose of our report was to evaluate safety and response with MIBG therapy followed by myeloablative busulfan and melphalan (BuMel) with ASCT in patients with refractory neuroblastoma. Retrospective chart review was done on patients treated with MIBG (18 mCi/kg) on Day 1 and ASCT on day 14. Six to eight weeks after MIBG, patients without progressive disease received IV busulfan on days -6 to -2 (target Css 700-900), melphalan (140 mg/m2 IV) on day -1, and ASCT on Day 0. Response and toxicity were evaluated after MIBG and again after myeloablative therapy. Eight patients completed MIBG/ASCT followed by BuMel/ASCT. MIBG was well tolerated, with grade 3 or 4 non-hematologic toxicity limited to one patient with sepsis. Grade 3 mucositis occurred in six patients after BuMel/ASCT. One patient developed sinusoidal obstructive syndrome (SOS) and died 50 days post-ASCT following myeloablative conditioning. All patients engrafted neutrophils (median 16.5 days) and platelets (median 32 days) after BuMel, excluding the patient with SOS. After all therapy, there were three complete, two partial, and one minor response in seven evaluable patients. MIBG at doses up to 18 mCi/kg can be safely administered 6 weeks prior to a BuMel consolidative regimen for refractory neuroblastoma. Preceding MIBG did not impair engraftment following BuMel. This regimen is being further evaluated in a Children's Oncology Group (COG) trial. Copyright © 2012 Wiley Periodicals, Inc.

Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients.

PubMed

Calvo-Río, Vanesa; Blanco, Ricardo; Santos-Gómez, Montserrat; Rubio-Romero, Esteban; Cordero-Coma, Miguel; Gallego-Flores, Adela; Veroz, Raúl; Torre, Ignacio; Hernández, Félix Francisco; Atanes, Antonio; Loricera, Javier; González-Vela, M C; Palmou, Natalia; Hernández, José L; González-Gay, Miguel A

2016-08-01

To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n = 8), psoriatic arthritis (n = 6) and non-radiographic axial SpA (n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n = 13), sulfasalazine (n = 6), pulses of methylprednisolone (n = 4), azathioprine (n = 3), leflunomide (n = 2), and cyclosporine (n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept (n = 7), adalimumab (n = 7), infliximab (n = 6), and certolizumab (n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy (n = 7) or in combination with conventional immunosuppressive drugs (n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0-0)] was significantly reduced compared to baseline findings [1 (0-3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Materials Problems in Chemical Liquid-Propellant Rocket Systems

NASA Technical Reports Server (NTRS)

Gilbert, L. L.

1959-01-01

With the advent of the space age, new adjustments in technical thinking and engineering experience are necessary. There is an increasing and extensive interest in the utilization of materials for components to be used at temperatures ranging from -423 to over 3500 deg F. This paper presents a description of the materials problems associated with the various components of chemical liquid rocket systems. These components include cooled and uncooled thrust chambers, injectors, turbine drive systems, propellant tanks, and cryogenic propellant containers. In addition to materials limitations associated with these components, suggested research approaches for improving materials properties are made. Materials such as high-temperature alloys, cermets, carbides, nonferrous alloys, plastics, refractory metals, and porous materials are considered.

Test model designs for advanced refractory ceramic materials

NASA Technical Reports Server (NTRS)

Tran, Huy Kim

1993-01-01

The next generation of space vehicles will be subjected to severe aerothermal loads and will require an improved thermal protection system (TPS) and other advanced vehicle components. In order to ensure the satisfactory performance system (TPS) and other advanced vehicle materials and components, testing is to be performed in environments similar to space flight. The design and fabrication of the test models should be fairly simple but still accomplish test objectives. In the Advanced Refractory Ceramic Materials test series, the models and model holders will need to withstand the required heat fluxes of 340 to 817 W/sq cm or surface temperatures in the range of 2700 K to 3000 K. The model holders should provide one dimensional (1-D) heat transfer to the samples and the appropriate flow field without compromising the primary test objectives. The optical properties such as the effective emissivity, catalytic efficiency coefficients, thermal properties, and mass loss measurements are also taken into consideration in the design process. Therefore, it is the intent of this paper to demonstrate the design schemes for different models and model holders that would accommodate these test requirements and ensure the safe operation in a typical arc jet facility.

Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.

PubMed

Oddo, Daniele; Siravegna, Giulia; Gloghini, Annunziata; Vernieri, Claudio; Mussolin, Benedetta; Morano, Federica; Crisafulli, Giovanni; Berenato, Rosa; Corti, Giorgio; Volpi, Chiara Costanza; Buscarino, Michela; Niger, Monica; Dunne, Philip D; Rospo, Giuseppe; Valtorta, Emanuele; Bartolini, Alice; Fucà, Giovanni; Lamba, Simona; Martinetti, Antonia; Di Bartolomeo, Maria; de Braud, Filippo; Bardelli, Alberto; Pietrantonio, Filippo; Di Nicolantonio, Federica

2017-07-25

Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF V600E and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown. We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation analyses in two bioptic specimens obtained at progression were used to confirm the plasma data. We identified in plasma MET gene hyper-amplification as a potential mechanism underlying therapy resistance. Increased MET gene copy and transcript levels were detected in liver and lymph node metastatic biopsies. Finally, transduction of MET in BRAF mutant colorectal cancer cells conferred refractoriness to BRAF and MET inhibition. We identified in a rectal cancer patient MET gene hyper-amplification as mechanism of resistance to dual BRAF and MET inhibition.

NASA Space Engineering Research Center for Utilization of Local Planetary Resources

NASA Technical Reports Server (NTRS)

Ramohalli, Kumar; Lewis, John S.

1991-01-01

In the processing of propellants, volatiles, and metals subject area, the following topics are discussed: reduction of lunar regolith; reduction of carbon dioxide; and reduction of carbonaceous materials. Other areas addressed include: (1) production of structural and refractory materials; (2) resource discovery and characterization; (3) system automation and optimization; and (4) database development. The majority of these topics are discussed with respect to the development of lunar and mars bases. Some main topics of interest include: asteroid resources, lunar resources, mars resources, materials processing, construction materials, propellant production, oxygen production, and space-based oxygen production plants.

Laser Surface Treatment of Sintered Alumina

NASA Astrophysics Data System (ADS)

Hagemann, R.; Noelke, C.; Kaierle, S.; Wesling, V.

Sintered alumina ceramics are used as refractory materials for industrial aluminum furnaces. In this environment the ceramic surface is in permanent contact with molten aluminum resulting in deposition of oxidic material on its surface. Consequently, a lower volume capacity as well as thermal efficiency of the furnaces follows. To reduce oxidic adherence of the ceramic material, two laser-based surface treatment processes were investigated: a powder- based single-step laser cladding and a laser surface remelting. Main objective is to achieve an improved surface quality of the ceramic material considering the industrial requirements as a high process speed.

Interface Analyses Between a Case-Hardened Ingot Casting Steel and Carbon-Containing and Carbon-Free Refractories

NASA Astrophysics Data System (ADS)

Fruhstorfer, Jens; Dudczig, Steffen; Rudolph, Martin; Schmidt, Gert; Brachhold, Nora; Schöttler, Leandro; Rafaja, David; Aneziris, Christos G.

2018-06-01

Corrosion tests of carbon-free and carbon-containing refractories were performed. The carbon-free crucibles corroded, whereas the carbon-containing crucibles were negligibly attacked. On them, inclusions were attached. This study investigates melt oxygen contents, interface properties, and steel compositions with their non-metallic inclusions in order to explore the inclusion formation and deposition mechanisms. The carbon-free crucibles were based on alumina, mullite, and zirconia- and titania-doped alumina (AZT). The carbon-containing (-C) ones were alumina-C and AZT-C. Furthermore, nanoscaled carbon and alumina additives (-n) were applied in an AZT-C-n material. In the crucibles, the case-hardened steel 17CrNiMo7-6 was remelted at 1580 °C. It was observed that the melt and steel oxygen contents were higher for the tests in the carbon-free crucibles. Into these crucibles, the deoxidizing alloying elements Mn and Si diffused. Reducing contents of deoxidizing elements resulted in higher steel oxygen levels and less inclusions, mainly of the inclusion group SiO2-core-MnS-shell (2.5 to 8 μ m). These developed from smaller SiO2 nuclei. The inclusion amount in the steel was highest after remelting in AZT-C-n for 30 minutes but decreased strongly with increasing remelting time (60 minutes) due to inclusions' deposition on the refractory surface. The Ti from the AZT and the nanoadditives supported inclusion growth and deposition. Other inclusion groups were alumina and calcium aluminate inclusions. Their contents were high after remelting in carbon- or AZT-containing crucibles but generally decreased during remelting. On the AZT-C-n crucible, a dense layer formed from vitreous compositions including Al, Ca, Mg, Si, and Ti. To summarize, for reducing forming inclusion amounts, mullite is recommended as refractory material. For capturing formed inclusions, AZT-C-n showed a high potential.

Shindand Airbase: Use of Open-Air Burn Pit Violated Department of Defense Requirements

DTIC Science & Technology

2014-07-01

discontinue the use of the burn pit as soon 7 A refractory liner is made from a cement -like...initial combustion), asbestos, mercury, foam tent material, or any item containing any of the above items. The instruction allows for a small

An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression

DTIC Science & Technology

2017-10-01

hormone -refractory prostate 543 carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-544 peptide loaded dendritic cells--a...as mRNA expression (Fig. 2A). Among three IFNs, IFNγ elevation is associated in PCa patients after radiation and hormonal therapy. We decided to...development. For example, a study has demonstrated that fibroblast growth factor 11 (FGF11) 321 released by the recruited CD4+ T cells can induce cell invasion

Molybdenum-copper and tungsten-copper alloys and method of making

DOEpatents

Schmidt, Frederick A.; Verhoeven, John D.; Gibson, Edwin D.

1989-05-23

Molybdenum-copper and tungsten-copper alloys are prepared by a consumable electrode method in which the electrode consists of a copper matrix with embedded strips of refractory molybdenum or tungsten. The electrode is progressively melted at its lower end with a superatmospheric inert gas pressure maintained around the liquifying electrode. The inert gas pressure is sufficiently above the vapor pressure of copper at the liquidus temperature of the alloy being formed to suppress boiling of liquid copper.

Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

PubMed

Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

2016-07-01

This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

Cost-effectiveness analysis of apatinib treatment for chemotherapy-refractory advanced gastric cancer.

PubMed

Chen, Hong-Dou; Zhou, Jing; Wen, Feng; Zhang, Peng-Fei; Zhou, Ke-Xun; Zheng, Han-Rui; Yang, Yu; Li, Qiu

2017-02-01

Apatinib, a third-line or later treatment for advanced gastric cancer (aGC), was shown to improve overall survival and progression-free survival (PFS) compared with placebo in the phase III trial. Given the modest benefit with high costs, we further evaluated the cost-effectiveness of apatinib for patients with chemotherapy-refractory aGC. A Markov model was developed to simulate the disease process of aGC (PFS, progressive disease, and death) and estimate the incremental cost-effectiveness ratio (ICER) of apatinib to placebo. The health outcomes and utility scores were derived from the phase III trial and previously published sources, respectively. Total costs were calculated from the perspective of the Chinese health-care payer. Sensitivity analysis was used to explore model uncertainties. Treatment with apatinib was estimated to provide an incremental 0.09 quality-adjusted life years (QALYs) at an incremental cost of $8113.86 compared with placebo, which resulted in an ICER of $90,154.00 per QALY. Sensitivity analysis showed that across the wide variation of parameters, the ICER exceeded the willingness-to-pay threshold of $23,700.00 per QALY which was three times the Gross Domestic Product per Capita in China. Apatinib is not a cost-effective option for patients with aGC who experienced failure of at least two lines chemotherapy in China. However, for its positive clinical value and subliminal demand, apatinib can provide a new therapeutic option.

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison.

PubMed

Keeping, Sam; Wu, Elise; Chan, Keith; Mojebi, Ali; Ferrante, Shannon Allen; Balakumaran, Arun

2018-05-15

There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study (Cheah et al., 2016) of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment. In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56-7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04-9.98]). These HRs increased to 5.16 (95% CI 3.61-7.38) and 6.56 (95% CI 4.01-10.72), respectively, in the secondary analysis. Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.

Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-20

B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

Radiative engineering with refractory epsilon-near-zero metamaterials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dyachenko, Pavel N.; Molesky, Sean; Petrov, Alexander Y.; Störmer, Michael; Krekeler, Tobias; Lang, Slawa; Ritter, Martin; Jacob, Zubin; Eich, Manfred

2016-04-01

Improvement in high-temperature stable spectrally selective absorbers and emitters is integral for the further development of thermophotovoltaic (TPV), lighting and solar thermal applications. However, the high operational temperatures (T>1000oC) required for efficient energy conversion, along with application specific criteria such as the operational range of low bandgap semiconductors, greatly restrict what can be accomplished with natural materials. Motivated by this challenge, we demonstrate the first example of high temperature thermal radiation engineering with metamaterials. By employing the naturally selective thermal excitation of radiative modes that occurs near topological transitions, we show that thermally stable highly selective emissivity features are achieved for temperatures up to 1000°C with low angular dependence in a sub-micron thick refractory tungsten/hafnium dioxide epsilon-near-zero (ENZ) metamaterial. We also investigate the main mechanisms of thermal degradation of the fabricated refractory metamaterial both in terms of optical performance and structural stability using spectral analysis and energy-dispersive X-ray spectroscopy (EDS) techniques. Importantly, we observe chemical stability of the constituent materials for temperatures up to 1000°C and structural stability beyond 1100°C. The scalable fabrication, requiring magnetron sputtering, and thermally robust optical properties of this metamaterial approach are ideally suited to high temperature emitter applications such as lighting or TPV. Our findings provide a first concrete proof of radiative engineering with high temperature topological transition in ENZ metamaterials, and establish a clear path for implementation in TPV energy harvesting applications.

Evaluation of Geopolymer Concrete for Rocket Test Facility Flame Deflectors

NASA Technical Reports Server (NTRS)

Allgood, Daniel C.; Montes, Carlos; Islam, Rashedul; Allouche, Erez

2014-01-01

The current paper presents results from a combined research effort by Louisiana Tech University (LTU) and NASA Stennis Space Center (SSC) to develop a new alumina-silicate based cementitious binder capable of acting as a high performance refractory material with low heat ablation rate and high early mechanical strength. Such a binder would represent a significant contribution to NASA's efforts to develop a new generation of refractory 'hot face' liners for liquid or solid rocket plume environments. This project was developed as a continuation of on-going collaborations between LTU and SSC, where test sections of a formulation of high temperature geopolymer binder were cast in the floor and walls of Test Stand E-1 Cell 3, an active rocket engine test stand flame trench. Additionally, geopolymer concrete panels were tested using the NASA-SSC Diagnostic Test Facility (DTF) thruster, where supersonic plume environments were generated on a 1ft wide x 2ft long x 6 inch deep refractory panel. The DTF operates on LOX/GH2 propellants producing a nominal thrust of 1,200 lbf and the combustion chamber conditions are Pc=625psig, O/F=6.0. Data collected included high speed video of plume/panel area and surface profiles (depth) of the test panels measured on a 1-inch by 1-inch giving localized erosion rates during the test. Louisiana Tech conducted a microstructure analysis of the geopolymer binder after the testing program to identify phase changes in the material.

Isotopic analysis of individual refractory metal nuggets using atom probe tomography

NASA Astrophysics Data System (ADS)

Daly, L.; Bland, P.; Schaefer, B. F.; Saxey, D. W.; Reddy, S.; Fougerouse, D.; William, R. D. A.; Forman, L. V.; Trimby, P.; La Fontaine, A.; Yang, L.; Cairney, J.; Ringer, S.

2016-12-01

Sub-micrometre metallic alloys of the highly siderophile elements, known as refractory metal nuggets (RMNs), can be found in primitive carbonaceous chondrites. There has been some suggestion that these grains may have a pre-solar origin, however their <1 µm size has meant that isotopic analysis of individual grains has not previously been possible. Atom probe microscopy has sufficient spatial resolution to quantify the isotopic compositions, across the entire mass range, of small sample volumes (<0.02 µm3) with high sensitivity and precision. We present analyses of four individual RMNs from the same refractory inclusion within the ALH 77307 meteorite. The results indicate that these RMNs have significant isotopic deviations from solar relative isotope abundances and therefore preserve a pre-solar isotopic signature. All RMNs exhibit large p-process enrichments in 98Ru and depletions in s-process 186Os. Two RMNs have a similar isotopic signature, suggesting formation in the same stellar environment. This similarity between two RMNs indicates that there may be a significant contribution of material to our solar system from a single source. The other two RMNs are isotopically dissimilar. Finally, three of the RMNs plot on a 187Re -187Os isochron from which we can derive a galactic age of 12.5 Ga ±1.8. To the best of our knowledge this is the first direct determination of the age of the Milky Way through physical analysis of non-solar material.

The efficacy of Ahmed glaucoma valve drainage devices in cases of adult refractory glaucoma in Indian eyes

PubMed Central

Parihar, Jitendra K S; Vats, Devendra P; Maggon, Rakesh; Mathur, Vijay; Singh, Anirudh; Mishra, Sanjay K

2009-01-01

Aim: To evaluate the efficacy of Ahmed glaucoma valve (AGV) drainage devices in cases of adult refractory glaucoma in Indian eyes. Settings and Design: Retrospective interventional case series study. Materials and Methods: Fifty two eyes of 32 patients of refractory glaucoma in the age group of 35 to 60 years who underwent AGV implantation with or without concomitant procedures from January 2003 to Jan 2007 were studied. Of these, 46 eyes (88%) had undergone filtering surgery earlier whereas remaining eyes underwent primary AGV implantation following failure of maximal medical therapy. The follow up ranged between 12 months to 48 months Results: Eighteen eyes (35%) had undergone phacoemulsification with AGV implantation, penetrating keratoplasty (PK) with AGV and intraocular lens (IOL) implantation in 13 eyes (25%), AGV over preexisting IOL in eight eyes (15%). AGV implantation alone was done in six (11%) eyes. Anterior chamber (AC) reconstruction with secondary IOL and AGV was performed in the remaining eyes. The mean intra ocular pressure (IOP) decreased from 36.3 ± 15.7 mm Hg to 19.6 ± 9.2 mm Hg. Complete success as per criteria was achieved in 46 eyes (88%). None of the eyes had failure to maintain IOP control following AGV. Conclusion: The AGV resulted in effective and sustained control of IOP in cases of adult refractory glaucoma in intermediate follow up. PMID:19700871

Rare-earth metals in nickel aluminide-based alloys: III. Structure and properties of multicomponent Ni3Al-based alloys

NASA Astrophysics Data System (ADS)

Bazyleva, O. A.; Povarova, K. B.; Kazanskaya, N. K.; Drozdov, A. A.

2009-04-01

The possibility of increasing the life of heterophase cast light Ni3Al-based superalloys at temperatures higher than 0.8 T m of Ni3Al is studied when their directional structure is additionally stabilized by nanoprecipitates, which form upon additional alloying of these alloys by refractory and active metals, and using special methods for preparing and melting of an alloy charge. The effect of the method of introducing the main components and refractory reaction-active and surface-active alloying elements into Ni3Al-based cast superalloys, which are thermally stable natural composite materials of the eutectic type, on the structure-phase state and the life of these alloys is studied. When these alloys are melted, it is necessary to perform a set of measures to form particles of refractory oxide cores covered with the β-NiAl phase and, then, γ'prim-Ni3Al phase precipitates during solidification. The latter phase forms the outer shell of grain nuclei, which provides high thermal stability and hot strength of an intermetallic compound-based alloy. As a result, a modified structure that is stabilized by the nanoprecipitates of nickel and aluminum lanthanides and the nanoprecipitates of phases containing refractory metals is formed. This structure enhances the life of the alloy at 1000 °C by a factor of 1.8-2.5.

Bauxite and alumina

USGS Publications Warehouse

Bray, E.L.

2012-01-01

The United States is import-reliant for nearly all of the bauxite that it consumes. Small amounts of bauxite and bauxitic clays are produced in Alabama, Arkansas and Georgia for nonmetallurgical uses. Metallurgical-grade bauxite (crude dry) imports in 2011 totaled 9.54 Mt (10.5 million st), 18 percent more than the quantity imported in 2010. Jamaica (54 percent). Guinea (25 percent) and Brazil (18 percent) were the leading suppliers to the United States in 2011. In 2011,117 kt (129,000 st) of refractory-grade calcined bauxite was imported, a 69-percent decrease compared with imports in 2010. This decrease was partly attributed to an increase in net imports of refractory products such as bricks and crucibles, which were 39 percent higher than in the prior year. Imports of refractory-grade calcined bauxite from Brazil declined by 99 percent and by 75 percent from Greece. Restrictions on exports of raw materials from China also might have contributed a small amount to the decrease in imports. Imports from China declined by 45 percent. Guyana (42 percent), China (35 percent) and Greece (22 percent) were the leading sources of U.S. refractory-grade calcined bauxite imports. Imports of nonrefractory-grade calcined bauxite in 2011 totaled 236 kt (260,000 st), 23 percent less than the quantity imported in 2010. Guyana (51 percent), Australia (37 percent) and China (7 percent) were the leading sources

Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

ClinicalTrials.gov

2017-07-14

Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2⁺ metastatic breast cancer.

PubMed

Wong, Hilda; Leung, Roland; Kwong, Ava; Chiu, Joanne; Liang, Raymond; Swanton, Charles; Yau, Thomas

2011-01-01

Human epidermal growth factor receptor (HER)-2(+) breast cancer is a distinct molecular and clinical entity, the prognosis of which is improved by trastuzumab. However, primary resistance to trastuzumab is observed in >50% of patients with HER-2(+) advanced breast cancer, and the majority of patients who initially respond to treatment eventually develop disease progression. To facilitate crosstrial comparisons and the understanding of resistance mechanisms, we propose a unifying definition of trastuzumab resistance as progression at first radiological reassessment at 8-12 weeks or within 3 months after first-line trastuzumab in the metastatic setting or new recurrences diagnosed during or within 12 months after adjuvant trastuzumab. In contrast, we define trastuzumab-refractory breast cancer as disease progression after two or more lines of trastuzumab-containing regimens that initially achieved disease response or stabilization at first radiological assessment. We review mechanisms of trastuzumab resistance mediated by p95HER-2 overexpression, phosphoinositide 3-kinase pathway activation, and signaling pathway activation driven by HER-3, epidermal growth factor receptor, and insulin-like growth factor 1 receptor. We distinguish in vitro from in vivo evidence, highlighting that most data describing trastuzumab resistance are derived from preclinical studies or small retrospective patient cohorts, and discuss targeted therapeutic approaches to overcome resistance. Prospective analysis through clinical trials with robust tissue collection procedures, prior to and following acquisition of resistance, integrated with next-generation tumor genome sequencing technologies, is identified as a priority area for development. The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies.

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

PubMed

Sugino, Kiminori; Nagahama, Mitsuji; Kitagawa, Wataru; Ohkuwa, Keiko; Uruno, Takashi; Matsuzu, Kenichi; Suzuki, Akifumi; Masaki, Chie; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Ogimi, Yuna; Ito, Koichi

2018-03-28

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

A rare single cytogenetic finding of isochromosome 14q in a female with refractory anemia with ring sideroblasts (RARS)

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

Haag, M.M.; Sutcliffe, M.J.; Nelson, R.P.

1994-09-01

Clonal cytogenetic abnormalities occur in 79% of patients with myelodysplastic syndrome (MDS) and can be used to diagnose malignancy. Some of these clonal chromosomal changes have been useful in evaluation of the pathobiological similarity between MDS and acute nonlymphocytic leukemia (ANLL) and can be used to monitor the disease progression. A 44-year-old woman, presenting with normochromic, normocytic anemia was clinically asymptomatic and physical examination revealed no lymphadenopathy or hepatosplenomegaly. Stains for iron demonstrated adequate stores but with numerours ring sideroblasts which constituted approximately 15% of the total erythoblastic population. No increased reticulum or fibrosis was noted. These findings supported amore » diagnosis of MDS, classification refractory anemia with ring sideroblasts (RARS). Bone marrow cytogentic analysis showed an isochromosome 14q as the sole chromosome abnormality and this was confirmed by molecular cytogenetics using a whole chromosome Coatasome probe for No. 14. A population of 46,XX cells (20%) was also observed. Numerous interphase cells had three isolated fluorescent signals for No. 14. Structural and numerical abnormalities of chromosome No. 14 are reported in many hematological disorders, but few structural abnormalities have been reported for RARS and no extra copies, including i(14q), have been reported for MD or RARS. However, examples of extra copies of No. 14, including the isochromosome form, have been reported for ANLL. Since 15% of RARS patients progress to ANLL, there may be prognostic significance to this chromosome abnormality for his patient. The patient is awaiting a suitable donor for bone marrow transplantation. The presence of isochromosome No. 14 in the malignant cells offers an opportunity to monitor disease progression pre-transplantation and minimal residual disease post-transplantation.« less

Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8).

PubMed

Emons, Günter; Kurzeder, Christian; Schmalfeldt, Barbara; Neuser, Petra; de Gregorio, Nikolaus; Pfisterer, Jacobus; Park-Simon, Tjoung-Won; Mahner, Sven; Schröder, Willibald; Lück, Hans-Joachim; Heubner, Martin Leonhard; Hanker, Lars; Thiel, Falk; Hilpert, Felix

2016-03-01

To evaluate activity and toxicity of mTOR inhibitor temsirolimus in patients with platinum-refractory/resistant ovarian cancer (OC) or advanced/recurrent endometrial carcinoma (EC). Women with epithelial ovarian, fallopian tube or primary peritoneal cancer were eligible, when they had progression during treatment with a platinum based regimen or within 6 months after receiving a platinum based regimen and a previous taxane treatment. Women with advanced/recurrent EC, no longer amenable to curative surgery and/or radiotherapy were eligible when they had no previous or only adjuvant chemotherapy. Preceding endocrine therapy for metastatic/recurrent disease was allowed. Patients received weekly IV infusions of 25mg temsirolimus. Primary endpoint was progression free survival rate after 4 months (OC) or 6 months (EC). A two stage design was applied. Forty-four patients (OC: n=22; EC: n=22) were enrolled and received temsirolimus treatment. Median age was 56 years (OC) or 63 years (EC). After eight weeks of treatment, 10 of 21 evaluable patients in the OC cohort and 8 of 20 evaluable patients in the EC cohort had progressive disease. Thus efficacy did not meet the predefined levels during the first stage of recruitment and the trial was stopped. Some patients in both cohorts had long lasting PFS (>7 months). Toxicity of temsirolimus was mild. Temsirolimus treatment was well tolerated in our patients, but did not meet the predefined efficacy criteria. In our study as in other trials on rapalogs in OC or EC, a few patients had long lasting disease stabilisations. Copyright © 2015. Published by Elsevier Inc.

Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells

PubMed Central

Mimeault, Murielle; Batra, Surinder K.

2012-01-01

Recent development of animal models relevant to human prostate cancer (PC) etiopathogenesis has provided important information on the specific functions provided by key gene products altered during disease initiation and progression to locally invasive, metastatic and hormone-refractory stages. Especially, the characterization of transgenic mouse models has indicated that the inactivation of distinct tumor suppressor proteins such as phosphatase tensin homolog deleted on chromosome 10 (PTEN), Nkx3.1, p27KIP1 and p53 and retinoblastoma (pRb) may cooperate for the malignant transformation of prostatic stem/progenitor cells into PC stem/progenitor cells and tumor development and metastases. Moreover, the sustained activation of diverse oncogenic signaling elements, including epidermal growth factor receptor (EGFR), sonic hedgehog, Wnt/β-catenin, c-Myc, Akt and nuclear factor-kappaB (NF-κB) also may contribute to the acquisition of more aggressive and hormone-refractory phenotypes by PC stem/progenitor cells and their progenies during disease progression. Importantly, it has also been shown that an enrichment of PC stem/progenitor cells expressing stem cell-like markers may occur after androgen deprivation therapy and docetaxel treatment in the transgenic mouse models of PC suggesting the critical implication of these immature PC cells in treatment resistance, tumor re-growth and disease recurrence. Of clinical interest, the molecular targeting of distinct gene products altered in PC cells by using different dietary compounds has also been shown to counteract PC initiation and progression in animal models supporting their potential use as chemopreventive or chemotherapeutic agents for eradicating the total tumor cell mass, improving current anti-hormonal and chemotherapies and preventing disease relapse. PMID:21396984

Materials Development for Hypersonic Flight Vehicles

NASA Technical Reports Server (NTRS)

Glass, David E.; Dirling, Ray; Croop, Harold; Fry, Timothy J.; Frank, Geoffrey J.

2006-01-01

The DARPA/Air Force Falcon program is planning to flight test several hypersonic technology vehicles (HTV) in the next several years. A Materials Integrated Product Team (MIPT) was formed to lead the development of key thermal protection system (TPS) and hot structures technologies. The technologies being addressed by the MIPT are in the following areas: 1) less than 3000 F leading edges, 2) greater than 3000 F refractory composite materials, 3) high temperature multi-layer insulation, 4) acreage TPS, and 5) high temperature seals. Technologies being developed in each of these areas are discussed in this paper.

METHOD OF MAKING REFRACTORY BODIES

DOEpatents

Andersen, J.C.

1960-05-31

A method is given for the manufacture of silicon carbide bodies that are characterized by high density, high purity, and superior resistance to oxidative deterioration. Dense silicon bodies are obtained by a process in which granular silicon carbide, a carbonizable material, and a carbonaceous material are mixed together, the mixture is shaped as desired, and then the shape is fired in the presence of more than the stoichiometric amount of silicon. The carbonizable material preferably includes a temporary binder that is set before the firing step to hold the mix in shape for firing.

First Ti-XANES analyses of refractory inclusions from Murchison

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

Simon, S.B.; Sutton, S.R.; Grossman, L.

2009-03-23

Ti valence in refractory phases is an important recorder of redox conditions in the early solar nebula. We report the valence of Ti in pyroxene, spinel and hibonite in spinel-hibonite and spinel-pyroxene inclusions and in a coarse hibonite grain. A system of solar composition is so reducing that Ti{sup 3+} and Ti{sup 4+} can coexist, making the valence of Ti a valuable indicator of f{sub O2} conditions during formation of nebular materials. The Ti{sup 3+}/Ti{sup 4+} ratios observed in the Ti-rich phases fassaite and rhoenite in coarse-grained refractory inclusions from CV3 chondrites have been shown to be quantitatively consistent withmore » formation in a gas of solar composition (log f{sub O2} = IW-6.8), but these are the only objects in chondrites for which this is the case. Here, we report the valence of Ti in various phases in refractory inclusions from the Murchison CM2 chondrite. The second-highest temperature, major-element-bearing phase predicted to condense from a gas of solar composition, hibonite (ideally CaAl{sub 12}O{sub 19}), can contain significant amounts of Ti, but the hibonite structure can have oxygen vacancies, so calculation of Ti valence from stoichiometry of electron probe analyses is not recommended for hibonite. To date, the only reported measurement of Ti valence in meteoritic hibonite was done by electron spin resonance, on coarse crystals from a Murchison hibonite-perovskite-melilite inclusion. Spinel and most of the pyroxene in CM inclusions contain too little Ti for derivation of Ti{sup 3+}/Ti{sup 4+} ratios from electron probe analyses. X-ray absorption near edge spectroscopy (XANES), however, allows determination of Ti valence in relatively Ti-poor phases. In the present work, we apply synchrotron microXANES to a large hibonite grain from Murchison and to spinel-hibonite (sp-hib) and spinel-pyroxene (sp-pyx) inclusions from Murchison, refractory materials whose Ti{sup 3+}/Ti{sup 4+} ratios have not been previously measured. Analysis of these samples allows comparison of Ti valence of (1) pyroxene in sp-pyx inclusions with that of fassaite; (2) spinel in hibonite-bearing with that of hibonite-free inclusions; and (3) hibonite in sp-hib inclusions with that of large, single grains and the previously analyzed sample.« less